Femoral neck fractures complicating Gaucher disease in children.

In normal children, fractures of the femoral neck are uncommon and accompany severe trauma and multiple injuries elsewhere in the skeleton [16, 17]. In children with Gaucher disease, a rare hereditary disorder of lipid metabolism, midcervical or basicervical fractures can occur with minor or no trauma and without other injury to the skeleton. Three children with Gaucher disease who developed pathologic fractures of the femoral neck are described. In all three, the fractures occurred between five and nine years of age, and the fracture lines passed through areas of abnormal bone characterized by poorly defined patches of increased and decreased density and cortical thinning along the medial femoral necks. In the affected hips, there was no evidence of avascular necrosis of the femoral heads at the time of injury. One child's fracture was preceded by multiple bone "crises" localized to the proximal femora.

In

    normal children
    AGE

,

    fractures of the femoral neck
    SYMPTOMS

 are uncommon and accompany

    severe trauma
    SYMPTOMS

 and

    multiple injuries elsewhere in the skeleton
    SYMPTOMS

 [16, 17]. In

    children
    AGE

 with

    Gaucher disease
    DIAGNOSIS

, a

    rare hereditary disorder of lipid metabolism
    GENETICS

,

    midcervical or basicervical fractures
    SYMPTOMS

 can occur with

    minor or no trauma
    NEG_FINDINGS

 and

    without other injury to the skeleton
    NEG_FINDINGS

. Three

    children
    AGE

 with

    Gaucher disease
    DIAGNOSIS

 who developed

    pathologic fractures of the femoral neck
    SYMPTOMS

 are described. In all three, the fractures occurred

    between five and nine years of age
    AGE

, and

    the fracture lines passed through areas of abnormal bone characterized by poorly defined patches of increased and decreased density and cortical thinning along the medial femoral necks
    SYMPTOMS

. In the affected hips, there was

    no evidence of avascular necrosis of the femoral heads at the time of injury
    NEG_FINDINGS

. One child's fracture was preceded by

    multiple bone "crises" localized to the proximal femora
    SYMPTOMS

.


Leukocyte beta-glucosidase in a child with Gaucher's disease and his kinship.

Beta-glucosidase was determined in leukocyte homogenates of a male child with Gaucher's disease and members of his family. An important difference in enzyme activity was found in the heterozygous gene carriers; in one obligate heterozygote, the mother, a high residual enzyme capacity was detected. Various methods of enzyme determination using various substrates are recommended for the detection of the gene carrier condition.

    Beta-glucosidase was determined in leukocyte homogenates
    BIOCHEMICAL

 of a

    male
    GENDER

    child
    AGE

 with

    Gaucher's disease
    DIAGNOSIS

 and members of his family. An important

    difference in enzyme activity
    BIOCHEMICAL

 was found in the

    heterozygous gene carriers
    GENETICS

; in one

    obligate heterozygote
    GENETICS

, the

    mother
    GENDER

, a

    high residual enzyme capacity
    BIOCHEMICAL

 was detected. Various methods of

    enzyme determination
    PARACLINICAL

 using various substrates are recommended for the detection of the gene carrier condition.

heterozygous gene carriers
obligate heterozygote


Neonatal ascites due to lysosomal storage disease.

The clinical and radiographic features of four newborns with lysosomal storage disease (LSD) in whom the dominant presenting clinical feature was ascites are presented. The diseases included infantile Gaucher disease, GM I gangliosidosis, infantile sialidosis, and Salla disease. Abdominal distention due to ascites and hepatosplenomegaly, and hypoplastic lungs were seen in all four infants. In the infant with Gaucher disease, the ribs and long bones were markedly thinned. Varying degrees of coarsening of the trabecular pattern of the bones and thinning of the cortex, and a lack of modeling were seen in all patients. Metaphyseal irregularity was noted in the patients with sialidosis and Salla disease. These skeletal radiographic findings may alert the radiologist to the cause for ascites in these patients, which is obscure. In all four patients, there was a history of perinatal death due to the same disease in a sibling; ascites was present in three of the siblings. The diagnosis was missed at autopsy in each of these siblings, underlining the lack of awareness of LSD as a cause for neonatal ascites.

The clinical and radiographic features of four

    newborns
    AGE

 with

    lysosomal storage disease (LSD)
    DIAGNOSIS

 in whom the dominant presenting clinical feature was

    ascites
    SYMPTOMS

 are presented. The diseases included

    infantile Gaucher disease
    DIAGNOSIS

,

    GM I gangliosidosis
    DIAGNOSIS

,

    infantile sialidosis
    DIAGNOSIS

, and

    Salla disease
    DIAGNOSIS

.

    Abdominal distention
    SYMPTOMS

 due to

    ascites
    SYMPTOMS

 and

    hepatosplenomegaly
    SYMPTOMS

, and

    hypoplastic lungs
    SYMPTOMS

 were seen in all four

    infants
    AGE

. In the

    infant
    AGE

 with

    Gaucher disease
    DIAGNOSIS

,

    the ribs and long bones were markedly thinned
    SYMPTOMS

.

    Varying degrees of coarsening of the trabecular pattern of the bones and thinning of the cortex
    SYMPTOMS

, and a

    lack of modeling
    SYMPTOMS

 were seen in all patients.

    Metaphyseal irregularity
    SYMPTOMS

 was noted in the patients with

    sialidosis
    DIAGNOSIS

 and

    Salla disease
    DIAGNOSIS

. These

    skeletal radiographic findings
    SYMPTOMS

 may alert the radiologist to the cause for

    ascites
    SYMPTOMS

 in these patients, which is obscure. In all four patients,

    there was a history of perinatal death due to the same disease in a sibling
    FAMILY

;

    ascites was present in three of the siblings
    FAMILY

.

    The diagnosis was missed
    FAMILY

 at

    autopsy
    PARACLINICAL

    in each of these siblings
    FAMILY

, underlining the lack of awareness of

    LSD
    DIAGNOSIS

 as a cause for

    neonatal
    AGE

    ascites
    DIAGNOSIS

.

lysosomal storage disease (LSD)
infantile Gaucher disease
GM I gangliosidosis
infantile sialidosis
Salla disease
Gaucher disease
sialidosis
Salla disease
LSD
ascites


Unusual pericardial calcification in Gaucher's disease.

Gaucher's disease is a hereditary metabolic disorder characterized by the abnormal accumulation of glucocerebrosides in reticuloendothelial cells. A 58-year-old man had Gaucher's disease and suffered from hypersplenism, cirrhosis of the liver, and free-floating calcifications in the pericardial space. The literature of the pericardial involvement in Gaucher's disease is reviewed.

    Gaucher's disease
    DIAGNOSIS

 is a

    hereditary metabolic disorder
    GENETICS

 characterized by the

    abnormal accumulation of glucocerebrosides in reticuloendothelial cells
    MICROSCOPIC

. A

    58-year-old
    AGE

    man
    GENDER

 had

    Gaucher's disease
    DIAGNOSIS

 and suffered from

    hypersplenism
    BIOCHEMICAL

,

    cirrhosis of the liver
    MICROSCOPIC

, and

    free-floating calcifications in the pericardial space
    SYMPTOMS

. The literature of the

    pericardial involvement
    SYMPTOMS

 in

    Gaucher's disease
    DIAGNOSIS

 is reviewed.

Gaucher's disease
Gaucher's disease
Gaucher's disease


Gaucher's disease in the black population of South Africa. A case report.

The diagnosis of the non-neuropathic form of Gaucher's disease was confirmed by haematological and enzymatic investigations in a Black girl. The aetiological relationship of this condition with Gaucher's disease in other populations is uncertain, but lack of expression of the enzyme defect in the white blood cells in our patient might be significant in this context. This case serves to emphasize that Gaucher's disease enters into the differential diagnosis of unexplained splenomegaly, irrespective of the ethnic background of the affected person.

The diagnosis of the

    non-neuropathic form of Gaucher's disease
    DIAGNOSIS

 was confirmed by

    haematological and enzymatic investigations
    PARACLINICAL

 in a

    Black
    ETHNICITY

    girl
    GENDER

. The aetiological relationship of this condition with

    Gaucher's disease
    DIAGNOSIS

 in other populations is uncertain, but

    lack of expression of the enzyme defect in the white blood cells
    BIOCHEMICAL

 in our patient might be significant in this context. This case serves to emphasize that

    Gaucher's disease
    DIAGNOSIS

 enters into the

    differential diagnosis
    PARACLINICAL

 of

    unexplained splenomegaly
    SYMPTOMS

, irrespective of the ethnic background of the affected person.


[Eye changes in Gaucher's disease].

In a patient with Gaucher's disease multiple, chalky-white, randomly distributed, circular spots were observed in the superficial layers of the retina or directly on the vessel walls. There are indications that these changes of the retina, which have also been described by other authors, are characteristic of the juvenile form of Gaucher's disease. By carrying out a long-term study over an 11-year period it was possible to prove that these spots were caused by defective healing of minute hemorrhages which were initially still visible as red and white concentric target lesions in the center of the spot. The macula was not cherry-red in this case.

In a patient with

    Gaucher's disease
    DIAGNOSIS

    multiple, chalky-white, randomly distributed, circular spots were observed in the superficial layers of the retina or directly on the vessel walls
    SYMPTOMS

. There are indications that these

    changes of the retina
    SYMPTOMS

, which have also been described by other authors, are characteristic of the

    juvenile form of Gaucher's disease
    DIAGNOSIS

. By carrying out a long-term study over an 11-year period it was possible to prove that

    these spots
    SYMPTOMS

 were caused by

    defective healing of minute hemorrhages which were initially still visible as red and white concentric target lesions in the center of the spot
    SYMPTOMS

.

    The macula was not cherry-red
    NEG_FINDINGS

 in this case.

Gaucher's disease
juvenile form of Gaucher's disease


Non-infantile neuronopathic Gaucher's disease: a clinicopathologic study.

Two siblings with Gaucher's disease developed a chronic, slowly progressive neurologic disorder in early adult life. Stimulus-sensitive myoclonus, generalized seizures, supranuclear gaze palsies, and cerebellar ataxia were the main clinical features. Autopsy disclosed perivascular Gaucher cells in the brain, and nerve cell loss and neuronophagia in the brainstem, cerebellum, and spinal cord. From these observations and the literature, there seem to be three clinically distinct neurologic syndromes in Gaucher's disease, depending on the age at which symptoms begin, but the neuropathologic changes are essentially the same in all of them. A modified classification of Gaucher's disease, based on these observations, is proposed.

Two

    siblings
    GENDER

 with

    Gaucher's disease
    DIAGNOSIS

 developed a

    chronic, slowly progressive neurologic disorder
    SYMPTOMS

 in

    early adult life
    AGE

.

    Stimulus-sensitive myoclonus
    SYMPTOMS

,

    generalized seizures
    SYMPTOMS

,

    supranuclear gaze palsies
    SYMPTOMS

, and

    cerebellar ataxia
    SYMPTOMS

 were the main clinical features.

    Autopsy
    PARACLINICAL

 disclosed

    perivascular Gaucher cells in the brain
    MICROSCOPIC

, and

    nerve cell loss and neuronophagia in the brainstem, cerebellum, and spinal cord
    MICROSCOPIC

. From these observations and the literature, there seem to be three clinically distinct

    neurologic syndromes
    SYMPTOMS

 in

    Gaucher's disease
    DIAGNOSIS

, depending on the age at which symptoms begin, but the

    neuropathologic changes
    SYMPTOMS

 are essentially the same in all of them. A modified classification of

    Gaucher's disease
    DIAGNOSIS

, based on these observations, is proposed.


Gaucher-like cells in a granular cell tumor.

The macrophages in connective tissue stroma and the tumor cells of granular cell tumors have many histochemical features similar to those of Gaucher cells. Ultrastructural examination of a granular cell tumor revealed the stromal cells to contain inclusions of various sizes and shapes. These inclusions, which contained macrophages, greatly resembled the Gaucher-like cells seen in various hematologic conditions and in lobomycosis. The Gaucher-like cells in the stroma of the granular cell tumor are formed presumably by the phagocytosis of material derived from the breakdown of the tumor cells, which are rich in glucoside and cerebroside.

    The macrophages in connective tissue stroma and the tumor cells of granular cell tumors
    MICROSCOPIC

 have

    many histochemical features similar to those of Gaucher cells
    MICROSCOPIC

.

    Ultrastructural examination
    PARACLINICAL

 of a

    granular cell tumor
    DIAGNOSIS

 revealed

    the stromal cells to contain inclusions of various sizes and shapes
    MICROSCOPIC

.

    These inclusions, which contained macrophages, greatly resembled the Gaucher-like cells seen in various hematologic conditions
    MICROSCOPIC

 and in

    lobomycosis
    DIAGNOSIS

.

    The Gaucher-like cells in the stroma of the granular cell tumor
    MICROSCOPIC

 are formed presumably by the

    phagocytosis of material derived from the breakdown of the tumor cells, which are rich in glucoside and cerebroside.
    MICROSCOPIC


Association of dysgerminoma and gaucher's disease.

A 22-year-old woman presented with splenomegaly and pancytopenia of over two years' duration. A splenectomy was performed because of a suspicion of Gaucher's disease. At the time of operation a left ovarian tumor was found and was removed. A diagnosis of Gaucher's disease was made on the basis of massive infiltration of histiocytes with typical cytoplasmic striations in the spleen, liver, and bone marrow. The ovarian tumor was characterized by a monotonous, diffuse proliferation of large, rounded cells and was diagnosed as dysgerminoma. The association of Gaucher's disease and malignant tumors is rare, only several cases have been reported in the English literature. An additional feature of this case was the appearance of histiocytes showing the characteristic cytoplasmic striations of Gaucher's cells in the stroma of the tumor.

A

    22-year-old
    AGE

    woman
    GENDER

 presented with

    splenomegaly
    SYMPTOMS

 and

    pancytopenia of over two years' duration
    BIOCHEMICAL

. A

    splenectomy
    MEDICATION

 was performed because of a suspicion of

    Gaucher's disease
    DIAGNOSIS

. At the time of operation a

    left ovarian tumor
    SYMPTOMS

 was found and was removed. A diagnosis of

    Gaucher's disease
    DIAGNOSIS

 was made on the basis of

    massive infiltration of histiocytes with typical cytoplasmic striations in the spleen, liver, and bone marrow
    MICROSCOPIC

. The

    ovarian tumor
    MICROSCOPIC

 was characterized by a

    monotonous, diffuse proliferation of large, rounded cells
    MICROSCOPIC

 and was diagnosed as

    dysgerminoma
    DIAGNOSIS

. The

    association of Gaucher's disease
    DIAGNOSIS

 and

    malignant tumors
    DIAGNOSIS

 is rare, only several cases have been reported in the English literature. An additional feature of this case was the

    appearance of histiocytes showing the characteristic cytoplasmic striations of Gaucher's cells in the stroma of the tumor
    MICROSCOPIC

.

Gaucher's disease
Gaucher's disease
dysgerminoma
association of Gaucher's disease
malignant tumors


Auditory brainstem response (ABR) in infantile Gaucher's disease.

The auditory brainstem response (ABR) was studied in an infant with Gaucher's disease. The infant was normal until the age of three months. His illness began with stridor, strabismus, inguinal hernia and failure to thrive. Thereafter, muscular rigidity with opisthotonus, ocular palsies, difficulty in swallowing and respiratory failure due to central origin developed. He died of respiratory failure due to central origin developed. He died of respiratory failure at the age of one year and four months. The ABR was abnormal at six and eight months of age. Initially, at the age of six months, there was a lengthening of the peak latencies of wave I, II and III and disappearance of the waves after IV. But at eight months, more marked lengthening of the peak latencies of the waves and the disappearance of waves after III were noted as his general condition deteriorated. The autopsy revealed relative preservation of the nuclei and tracts of the auditory pathways in the brainstem. The ABR was useful for monitoring the progress of the disease in this patient because it made detection of brainstem lesions possible.

The

    auditory brainstem response (ABR)
    PARACLINICAL

 was studied in an

    infant
    AGE

 with

    Gaucher's disease
    DIAGNOSIS

. The

    infant
    AGE

 was normal

    until the age of three months
    AGE

. His illness began with

    stridor
    SYMPTOMS

,

    strabismus
    SYMPTOMS

,

    inguinal hernia
    SYMPTOMS

 and

    failure to thrive
    SYMPTOMS

. Thereafter,

    muscular rigidity
    SYMPTOMS

 with

    opisthotonus
    SYMPTOMS

,

    ocular palsies
    SYMPTOMS

,

    difficulty in swallowing
    SYMPTOMS

 and

    respiratory failure due to central origin
    SYMPTOMS

 developed.

    He
    GENDER

    died
    SYMPTOMS

 of

    respiratory failure due to central origin developed
    SYMPTOMS

.

    He
    GENDER

    died
    SYMPTOMS

 of

    respiratory failure
    SYMPTOMS

    at the age of one year and four months
    AGE

. The

    ABR was abnormal
    SYMPTOMS

    at six and eight months of age
    AGE

. Initially, at the

    age of six months
    AGE

, there was a

    lengthening of the peak latencies of wave I, II and III and disappearance of the waves after IV
    SYMPTOMS

. But

    at eight months
    AGE

,

    more marked lengthening of the peak latencies of the waves and the disappearance of waves after III
    SYMPTOMS

 were noted as his general condition deteriorated. The

    autopsy
    PARACLINICAL

 revealed

    relative preservation of the nuclei and tracts of the auditory pathways in the brainstem
    SYMPTOMS

. The ABR was useful for monitoring the progress of the disease in this patient because it made detection of

    brainstem lesions
    SYMPTOMS

 possible.


Acquired Gaucher's cells in Hodgkin's disease.

A patient with Hodgkin's disease associated with low glucocerebrosidase levels in the peripheral leukocytes, and Gaucher's cells in the bone marrow and lymph nodes, is described. After MOPP therapy, complete remission of Hodgkin's disease was accompanied by normalization of the glucocerebrosidase level and disappearance of Gaucher's cells. This observation appears unique when compared with the four cases of combined Hodgkin's and Gaucher's disease reported in earlier literature in which Gaucher's disease remained unchanged after chemotherapy. We conclude that our patient had Hodgkin's disease and acquired Gaucher's cells with diminished glucocerebrosidase levels, rather than a combination of Hodgkin's disease and Gaucher's disease.

A patient with

    Hodgkin's disease
    DIAGNOSIS

 associated with

    low glucocerebrosidase levels in the peripheral leukocytes
    BIOCHEMICAL

    , and Gaucher's cells in the bone marrow and lymph nodes
    MICROSCOPIC

, is described. After

    MOPP therapy
    MEDICATION

,

    complete remission of Hodgkin's disease
    MEDICATION

 was accompanied by

    normalization of the glucocerebrosidase level
    BIOCHEMICAL

 and

    disappearance of Gaucher's cells
    MICROSCOPIC

. This observation appears unique when compared with the four cases of

    combined Hodgkin's and Gaucher's disease
    DIAGNOSIS

 reported in earlier literature in which

    Gaucher's disease remained unchanged
    MICROSCOPIC

    after chemotherapy
    NEG_FINDINGS

. We conclude that our patient had

    Hodgkin's disease
    DIAGNOSIS

 and

    acquired Gaucher's cells with diminished glucocerebrosidase levels
    MICROSCOPIC

, rather than a

    combination of Hodgkin's disease and Gaucher's disease
    DIAGNOSIS

.

MOPP therapy
complete remission of Hodgkin's disease


[Gaucher's disease: hemorrhagic diathesis and term pregnancy with the birth of a malformed fetus].

A patient suffering from Gaucher's disease observed for the first time five years age while in pregnancy and observed again during a second pregnancy ended with the delivery of a malformed female infant is presented. Laboratory findings of this case and their correlation with the clinical manifestations of this disease are underlined. Occurrence of foetal malformations in this disease is also discussed.

A patient suffering from

    Gaucher's disease
    DIAGNOSIS

 observed for the first time

    five years age
    AGE

 while in

    pregnancy
    AGE

 and observed again during a second

    pregnancy
    DIAGNOSIS

 ended with the delivery of a

    malformed female infant
    SYMPTOMS

 is presented. Laboratory findings of this case and their correlation with the clinical manifestations of this disease are underlined. Occurrence of

    foetal malformations
    SYMPTOMS

 in this disease is also discussed.

malformed female infant
foetal malformations


Histologic and histochemical investigation of Gaucher cells.

Electron microscopic investigations suggest that morphologically, Gaucher cells and histiocytes are very similar. The fact that there are tubular elements in the lysosomes strongly suggests the possibility of lysosomes as the precursors of Gaucher bodies. By means of the lectin staining methods, the localization of glucocerebroside is clearly demonstrable in Gaucher cells. Lectin staining is the significant diagnostic feature of both Gaucher's and Krabbe's diseases.

    Electron microscopic investigations
    PARACLINICAL

 suggest that

    morphologically, Gaucher cells and histiocytes are very similar
    MICROSCOPIC

. The fact that

    there are tubular elements in the lysosomes
    MICROSCOPIC

 strongly suggests the possibility of

    lysosomes as the precursors of Gaucher bodies
    MICROSCOPIC

. By means of the

    lectin staining methods
    PARACLINICAL

, the

    localization of glucocerebroside is clearly demonstrable in Gaucher cells
    MICROSCOPIC

.

    Lectin staining
    MICROSCOPIC

 is the significant diagnostic feature of both

    Gaucher's and Krabbe's diseases
    DIAGNOSIS

.


[Neonatal hepatitis in a case of Gaucher's disease in its acute infantile form].

There is described a case of Gaucher's disease in its acute infantile form, interesting for the initial symptomatology marked by a hepatitic similarity, which has got manifest, already during the first days of life. A splenic and hepatic biopsy made at the age of about six months showed clearly the presence of cells with the characteristics of Gaucher's cells. A sure diagnosis was made at seven months through the determination of beta-glucosidase on the fibroblasts after the skin-biopsy. The patient died at the age of 14 months during an apnoic crisis.

There is described a case of

    Gaucher's disease
    DIAGNOSIS

 in its

    acute infantile form
    DIAGNOSIS

, interesting for the initial symptomatology marked by a

    hepatitic similarity
    SYMPTOMS

, which has got manifest, already

    during the first days of life
    AGE

. A

    splenic and hepatic biopsy
    PARACLINICAL

 made at the

    age of about six months
    AGE

 showed clearly the

    presence of cells with the characteristics of Gaucher's cells
    MICROSCOPIC

. A sure diagnosis was made

    at seven months
    AGE

 through the

    determination of beta-glucosidase on the fibroblasts
    PARACLINICAL

 after the

    skin-biopsy
    PARACLINICAL

. The patient

    died
    SYMPTOMS

 at the

    age of 14 months
    AGE

 during an

    apnoic crisis
    SYMPTOMS

.


Coexistence of Gaucher Disease and Philadelphia positive chronic granulocytic leukemia.

A patient with coexistent Gaucher disease and Philadelphia positive chronic granulocytic leukemia (CGL), who subsequently developed myeloblastic leukemia, is described. The diagnosis of CGL was established according to standard clinical, morphological, biochemical, and cytogenetic data, while the diagnosis of true Gaucher disease was based on biochemical data and the presence of Gaucher cells with typical ultrastructural features in the bone marrow and spleen. Enzyme studies showed low activity of ceramide-beta-glucosidase in the patient's peripheral blood leukocytes, skin fibroblasts, and splenic tissue and the presence of increased amounts of ceramide-beta-glucoside in the spleen. This case is reported in order to draw attention to the possible coexistence of these two diseases in the same patient, as opposed to the well-recognized finding of "Gaucher-like" cells in the bone marrow of patients with CGL. Enzyme studies enable distinction between these two situations.

A patient with

    coexistent Gaucher disease and Philadelphia positive chronic granulocytic leukemia (CGL)
    DIAGNOSIS

, who subsequently developed

    myeloblastic leukemia
    DIAGNOSIS

, is described. The diagnosis of

    CGL
    DIAGNOSIS

 was established according to standard clinical, morphological, biochemical, and cytogenetic data, while the diagnosis of

    true Gaucher disease
    DIAGNOSIS

 was based on

    biochemical data
    PARACLINICAL

 and the

    presence of Gaucher cells with typical ultrastructural features in the bone marrow and spleen
    MICROSCOPIC

.

    Enzyme studies
    PARACLINICAL

 showed

    low activity of ceramide-beta-glucosidase in the patient's peripheral blood leukocytes, skin fibroblasts, and splenic tissue
    BIOCHEMICAL

 and the

    presence of increased amounts of ceramide-beta-glucoside in the spleen
    MICROSCOPIC

. This case is reported in order to draw attention to the possible coexistence of these two diseases in the same patient, as opposed to the well-recognized finding of

    "Gaucher-like" cells in the bone marrow
    MICROSCOPIC

 of patients with

    CGL
    DIAGNOSIS

.

    Enzyme studies
    PARACLINICAL

 enable distinction between these two situations.


Gaucher's disease and glioblastoma multiforme in two siblings: a clinicopathologic study.

The clinical and pathologic features of two brothers with the adult form of Gaucher's disease, both of whom developed cerebral glioblastoma multiforme, are presented. Neither patient had a long-standing neurologic disorder, and morphologic evidence of nervous system glucocerebroside storage was not seen. Despite the known increased incidence of malignancy in Gaucher's disease, a review of the literature and of sixty-two Mayo Clinic cases of adult onset Gaucher's disease revealed only one other instance of the association with glioma. The significance of the relationship is unknown.

The clinical and pathologic features of two

    brothers
    GENDER

 with the

    adult form of Gaucher's disease
    DIAGNOSIS

, both of whom developed

    cerebral glioblastoma multiforme
    DIAGNOSIS

, are presented. Neither patient had a

    long-standing neurologic disorder
    NEG_FINDINGS

, and

    morphologic evidence of nervous system glucocerebroside storage was not seen
    NEG_FINDINGS

. Despite the known increased incidence of

    malignancy
    DIAGNOSIS

 in

    Gaucher's disease
    DIAGNOSIS

, a review of the literature and of sixty-two Mayo Clinic cases of

    adult onset Gaucher's disease
    AGE

 revealed only one other instance of the association with

    glioma
    DIAGNOSIS

. The significance of the relationship is unknown.

adult form of Gaucher's disease
cerebral glioblastoma multiforme
malignancy
Gaucher's disease
glioma


Ocular motor signs in some metabolic diseases.

Ocular motor disturbances are described with a miscellany of metabolic disturbances. Horizontal gaze abnormalities, often simulating congenital ocular motor apraxia, characterized Gaucher's disease. Vertical gaze abnormalities, especially downgaze paralysis, characterized what is generally considered a variant of Niemann-Pick disease, or sea-blue histiocytosis, but which we prefer to call the "DAF" syndrome. A form of internuclear ophthalmoplegia but with nystagmus of the adducting eye characterized abetalipoproteinemia. epileptiform eyelid and eye movements occurred in a case of methylmalonohomocystinuria. Ocular motor abnormalities are also described with variation of olivopontocerebellar degeneration and with ataxia telangiectasia.

    Ocular motor disturbances
    SYMPTOMS

 are described with a miscellany of

    metabolic disturbances
    SYMPTOMS

.

    Horizontal gaze abnormalities
    SYMPTOMS

, often simulating

    congenital ocular motor apraxia
    SYMPTOMS

, characterized

    Gaucher's disease
    DIAGNOSIS

.

    Vertical gaze abnormalities
    SYMPTOMS

, especially

    downgaze paralysis
    SYMPTOMS

, characterized what is generally considered a variant of

    Niemann-Pick disease
    DIAGNOSIS

, or

    sea-blue histiocytosis
    DIAGNOSIS

, but which we prefer to call the "

    DAF" syndrome
    DIAGNOSIS

. A form of

    internuclear ophthalmoplegia
    SYMPTOMS

 but with

    nystagmus of the adducting eye
    SYMPTOMS

 characterized

    abetalipoproteinemia
    DIAGNOSIS

.

    epileptiform eyelid and eye movements
    SYMPTOMS

 occurred in a case of

    methylmalonohomocystinuria
    DIAGNOSIS

.

    Ocular motor abnormalities
    SYMPTOMS

 are also described with

    variation of olivopontocerebellar degeneration
    DIAGNOSIS

 and with

    ataxia telangiectasia
    DIAGNOSIS

.

Ocular motor disturbances
metabolic disturbances
Horizontal gaze abnormalities
congenital ocular motor apraxia
Vertical gaze abnormalities
downgaze paralysis
internuclear ophthalmoplegia
nystagmus of the adducting eye
epileptiform eyelid and eye movements
Ocular motor abnormalities


Pyogenic osteomyelitis versus pseudo-osteomyelitis in Gaucher's disease. Report of a case and review of the literature.

Presented is a young girl with Gaucher's disease who developed acute bone pain accompanied by signs of inflammation and who was felt to have possible pyogenic osteomyelitis. The lack of significant pathogenic bacterial growth on culture and the findings at orthopedic surgery led the authors to conclude that this child probably represented a case of pseudo-osteomyelitis, but the isolation of an anaerobe from the operative culture of the involved bone leaves the exact diagnosis unclear. Since this child underwent an open surgical procedure, she was treated with antibiotics to prevent the possible development of chronic osteomyelitis. This anaerobic growth on culture, although strongly felt to be a contaminant, also played a role in this decision. She had an uneventful hospital course and subsequently has done well. It is suggested that great caution be taken before subjecting a patient with Gaucher's disease to orthopedic surgical procedures. If pyogenic osteomyelitis is strongly suspected, obtaining multiple blood cultures and culture by needle aspirate may be preferred over an open surgical procedure. The use of empiric antibiotic therapy without an attempt at further diagnosis is not recommended. If an orthopedic surgical procedure is necessary in a patient with Gaucher's disease, antibiotic coverage is indicated and long-term observation of the operative sight for drainage and/or other signs of chronic inflammatory changes in mandatory.

Presented is a

    young
    AGE

    girl
    GENDER

 with

    Gaucher's disease
    DIAGNOSIS

 who developed

    acute bone pain
    SYMPTOMS

 accompanied by

    signs of inflammation
    SYMPTOMS

 and who was felt to have possible

    pyogenic osteomyelitis
    DIAGNOSIS

. The

    lack of significant pathogenic bacterial growth on culture
    NEG_FINDINGS

 and the findings at

    orthopedic surgery
    PARACLINICAL

 led the authors to conclude that this

    child
    AGE

 probably represented a case of

    pseudo-osteomyelitis
    DIAGNOSIS

, but the

    isolation of an anaerobe
    MICROSCOPIC

    from the operative culture of the involved bone
    PARACLINICAL

 leaves the exact diagnosis unclear. Since this

    child
    AGE

 underwent an

    open surgical procedure
    MEDICATION

,

    she
    GENDER

 was

    treated with antibiotics
    MEDICATION

 to prevent the possible development of

    chronic osteomyelitis
    DIAGNOSIS

. This

    anaerobic growth on culture
    SYMPTOMS

,

    although strongly felt to be a contaminant
    NEG_FINDINGS

, also played a role in this decision.

    She
    GENDER

 had an uneventful hospital course and subsequently has done well. It is suggested that great caution be taken before subjecting a patient with

    Gaucher's disease
    DIAGNOSIS

 to

    orthopedic surgical procedures
    MEDICATION

. If

    pyogenic osteomyelitis
    DIAGNOSIS

 is strongly suspected,

    obtaining multiple blood cultures and culture by needle aspirate
    PARACLINICAL

 may be preferred over an

    open surgical procedure
    MEDICATION

. The use of

    empiric antibiotic therapy
    MEDICATION

    without an attempt at further diagnosis
    NEG_FINDINGS

 is not recommended. If an

    orthopedic surgical procedure
    MEDICATION

 is necessary in a patient with

    Gaucher's disease
    DIAGNOSIS

,

    antibiotic coverage
    MEDICATION

 is indicated and

    long-term observation of the operative sight for drainage
    PARACLINICAL

 and/or other signs of

    chronic inflammatory changes
    SYMPTOMS

 in mandatory.

Gaucher's disease
pyogenic osteomyelitis
pseudo-osteomyelitis
chronic osteomyelitis
Gaucher's disease
pyogenic osteomyelitis
Gaucher's disease

acute bone pain
signs of inflammation
anaerobic growth on culture
chronic inflammatory changes

open surgical procedure
treated with antibiotics
orthopedic surgical procedures
open surgical procedure
empiric antibiotic therapy
orthopedic surgical procedure
antibiotic coverage


Pseudo-Gaucher cell in IgMk plasmacytoid lymphoma.

Cells resembling those of Gaucher's disease were found on imprints of a lymph node from a patient with a plasmacytoid lymphoma. These cells contained nonspecific esterase, and electron-dense crystal-like structures. Associated plasma cells stained positively with anti-kappa and anti-mu sera but few macrophages were stained. The resemblance of these macrophages to Gaucher cells was due to the crystal-like inclusions that probably represented altered immunoglobulin.

    Cells resembling those of Gaucher's disease
    MICROSCOPIC

 were

    found on imprints of a lymph node
    MICROSCOPIC

 from a patient with a

    plasmacytoid lymphoma
    MICROSCOPIC

. These

    cells contained nonspecific esterase, and electron-dense crystal-like structures
    MICROSCOPIC

.

    Associated plasma cells stained positively with anti-kappa and anti-mu sera
    MICROSCOPIC

 but

    few macrophages were stained
    NEG_FINDINGS

. The

    resemblance of these macrophages to Gaucher cells
    MICROSCOPIC

 was due to the

    crystal-like inclusions
    MICROSCOPIC

 that probably represented

    altered immunoglobulin.
    MICROSCOPIC


Renal involvement in Gaucher's disease.

A patient with chronic Gaucher's disease is described who developed glomerulopathy 24 years after splenectomy terminating in renal failure. The pathological changes of this very rare complication of Gaucher's disease are described. The few similar cases reported in the literature are reviewed and the possible pathogenetic pathways discussed.

A patient with

    chronic Gaucher's disease
    DIAGNOSIS

 is described who developed

    glomerulopathy
    DIAGNOSIS

 24 years after

    splenectomy
    MEDICATION

 terminating in

    renal failure
    SYMPTOMS

. The pathological changes of this very rare complication of

    Gaucher's disease
    DIAGNOSIS

 are described. The few similar cases reported in the literature are reviewed and the possible pathogenetic pathways discussed.

chronic Gaucher's disease
glomerulopathy
Gaucher's disease


Electron microscopic studies in lipid storage disease.

Biopsy and autopsy specimens from patients with Gaucher's disease and Niemann-Pick disease were studied ultrastructurally. The morphological features were compared with those obtained from paraffin-embedded tissues after reprocessing the tissue for electron microscopy. With routine glutaraldehyde-osmium fixation, both surgical and autopsy specimens from Gaucher's disease showed cytoplasmic bodies containing elongated tubular structures with a translucent appearance. Tissue processed from paraffin-embedded blocks showed moderate preservation of the cytoplasmic glucocerebroside-containing bodies in Gaucher's disease. Routine fixation for electron microscopy of surgical of surgical and autopsy specimens from Niemann-Pick disease showed characteristic cytoplasmic vacuolated formations which were frequently multilaminated. These sphingomyelin-containing vacuoles were poorly preserved in tissue reprocessed from paraffin blocks.

    Biopsy and autopsy specimens
    PARACLINICAL

 from patients with

    Gaucher's disease
    DIAGNOSIS

 and

    Niemann-Pick disease
    DIAGNOSIS

 were studied

    ultrastructurally
    PARACLINICAL

. The morphological features were compared with those obtained from

    paraffin-embedded tissues
    PARACLINICAL

 after

    reprocessing the tissue for electron microscopy
    PARACLINICAL

. With

    routine glutaraldehyde-osmium fixation
    PARACLINICAL

, both

    surgical and autopsy specimens
    PARACLINICAL

 from

    Gaucher's disease
    DIAGNOSIS

 showed

    cytoplasmic bodies containing elongated tubular structures with a translucent appearance
    MICROSCOPIC

.

    Tissue processed from paraffin-embedded blocks
    PARACLINICAL

 showed

    moderate preservation of the cytoplasmic glucocerebroside-containing bodies in Gaucher's disease
    MICROSCOPIC

.

    Routine fixation for electron microscopy of surgical of surgical and autopsy specimens
    PARACLINICAL

 from

    Niemann-Pick disease
    DIAGNOSIS

 showed

    characteristic cytoplasmic vacuolated formations which were frequently multilaminated
    MICROSCOPIC

.

    These sphingomyelin-containing vacuoles were poorly preserved in tissue reprocessed from paraffin blocks
    MICROSCOPIC

.

Gaucher's disease
Niemann-Pick disease
Gaucher's disease
Niemann-Pick disease


[Portal hypertension complicating Gaucher's disease (author's transl)].

On the occasion of a case of Gaucher's disease associated with portal hypertension and after reviewing similar cases in the literature, the following conclusions can be proposed: portal hypertension is a very rare complication of Gaucher's disease. An intrahepatic block or, more rarely, a constrictive pericarditis should be discussed. Splenectomy, which could be responsible for postoperative portal thrombosis, should be carried out only in patients with severe hypersplenism. In cases with proven portal hypertension, the indication for portacaval shunting should take into account the peculiar circumstances related to Gaucher's disease.

On the occasion of a case of

    Gaucher's disease associated with portal hypertension
    DIAGNOSIS

 and after reviewing similar cases in the literature, the following conclusions can be proposed:

    portal hypertension
    SYMPTOMS

 is a very rare complication of

    Gaucher's disease
    DIAGNOSIS

. An

    intrahepatic block
    SYMPTOMS

 or, more rarely, a

    constrictive pericarditis
    DIAGNOSIS

 should be discussed.

    Splenectomy
    MEDICATION

, which could be responsible for

    postoperative portal thrombosis
    SYMPTOMS

, should be carried out only in patients with

    severe hypersplenism
    BIOCHEMICAL

. In cases with proven

    portal hypertension
    SYMPTOMS

, the indication for

    portacaval shunting
    MEDICATION

 should take into account the peculiar circumstances related to

    Gaucher's disease
    DIAGNOSIS

.

portal hypertension
intrahepatic block
postoperative portal thrombosis
portal hypertension


Total hip replacement in Gaucher's disease.

We performed seven total hip replacements in six patients with the adult form of Gaucher's disease. Excessive perioperative hemorrhage was a common complication, and three patients have required revision of loosened components. Two of these were young patients with a more severe form of the disease. Total hip replacement is feasible and likely to be successful in the older patient with Gaucher's disease and osteonecrosis or failed prior hip surgery.

We performed seven

    total hip replacements
    MEDICATION

 in six patients with the

    adult form of Gaucher's disease
    DIAGNOSIS

.

    Excessive perioperative hemorrhage
    SYMPTOMS

 was a common complication, and three patients have required

    revision of loosened components
    MEDICATION

. Two of these were

    young
    AGE

 patients with a more severe form of the disease.

    Total hip replacement
    MEDICATION

 is feasible and likely to be successful in the

    older
    AGE

 patient with

    Gaucher's disease
    DIAGNOSIS

 and

    osteonecrosis
    DIAGNOSIS

 or

    failed prior hip surgery
    MEDICATION

.

total hip replacements
revision of loosened components
Total hip replacement
failed prior hip surgery

adult form of Gaucher's disease
Gaucher's disease
osteonecrosis


Gaucher's disease. I. Modern enzymatic and anatomic methods of diagnosis.

The physician who diagnoses Gaucher's disease should take advantage of the noninvasive method that analyzes WBCs for residual beta-glucocerebrosidase and beta-glucosidase activities. When this method is carried out in conjunction with the measurement of serum acid phosphatase levels, a bone marrow examination may be unnecessary. With this method, we studied an adult who had mild splenomegaly and abdominal pain. When bone marrow was finally obtained subsequent to diagnosis by the enzymatic analysis, the deposits that are specifically formed in Gaucher's disease were easily demonstrated by electron microscopy. We believe that these methods are more specific for the diagnosis of Gaucher's disease than is the light microscopic finding of bone marrow cells that have abundant and striated cytoplasm.

The physician who diagnoses

    Gaucher's disease
    DIAGNOSIS

 should take advantage of the noninvasive method that

    analyzes WBCs
    BIOCHEMICAL

 for

    residual beta-glucocerebrosidase and beta-glucosidase activities
    BIOCHEMICAL

. When this method is carried out in conjunction with the

    measurement of serum acid phosphatase levels
    PARACLINICAL

, a

    bone marrow examination
    PARACLINICAL

 may be unnecessary. With this method, we studied an

    adult
    AGE

 who had

    mild splenomegaly
    SYMPTOMS

 and

    abdominal pain
    SYMPTOMS

. When

    bone marrow was
    PARACLINICAL

 finally obtained subsequent to diagnosis by the

    enzymatic analysis
    PARACLINICAL

,

    the deposits that are specifically formed in Gaucher's disease
    MICROSCOPIC

 were easily demonstrated by

    electron microscopy
    PARACLINICAL

. We believe that these methods are more specific for the diagnosis of

    Gaucher's disease
    DIAGNOSIS

 than is the light microscopic finding of

    bone marrow cells that have abundant and striated cytoplasm
    MICROSCOPIC

.


Fundal abnormalities of Gaucher's disease.

The evidence for cherry-red maculas in Gaucher's disease is questionable, but in occasional patients, scattered white spots in and on the retina appear to be characteristic. These white spots consist of clusters of swollen histiocytes (Gaucher cells).

The evidence for

    cherry-red maculas
    SYMPTOMS

 in

    Gaucher's disease
    DIAGNOSIS

 is questionable, but in occasional patients,

    scattered white spots in and on the retina
    SYMPTOMS

 appear to be characteristic. These

    white spots
    MICROSCOPIC

 consist of

    clusters of swollen histiocytes (Gaucher cells)
    MICROSCOPIC

.


Niemann-Pick disease, Type C: evidence for the deficiency of an activating factor stimulating sphingomyelin and glucocerebroside degradation.

1) Qualitative lipid analyses by thin-layer chromatography of 4 Niemann-Pick type C spleens confirmed sphingomyelin accumulation together with increase in the amount of glucocerebroside. 2) In the presence of crude sodium taurocholate as detergent, sphingomyelin degradation rates of normal and Niemann-Pick type C-cultured fibroblasts were fairly close under standard conditions at pH 5.0. In the absence of sodium taurocholate, sphingomyelinase activity was optimal at pH 4.0. Sphingomyelinase activities of fibroblasts from two patients with Niemann-Pick disease type C measured without detergent, were about 30% of that of controls. 3) Extracts from Gaucher spleen heated to 90 degrees C and devoid of sphingomyelinase activity stimulated at the optimal pH of 4.0 sphingomyelin degradation by cultured normal fibroblasts (2--4-fold, Niemann-Pick type C fibroblasts (5--9-fold), whereas similarly treated extracts from Niemann-Pick type C spleen showed no stimulation of sphingomyelin catabolism. Heated extracts from normal human spleen exhibited a smaller stimulation than that shown by Gaucher spleen. This stimulating effect could not be observed in fibroblasts from patients suffering from Niemann-Pick type B (sphingomyelinase defect). 4) Heat-treated extracts of Gaucher spleen were fractionated by ion exchange chromatography, isoelectric focusing and gel filtration. The active fractions obtained by these procedures stimulated sphingomyelin as well as glucocerebroside degradation and were absent from the corresponding Niemann-Pick type C preparations. Enriched activator preparations of Gaucher spleen stimulated sphingomyelinase activity of Niemann-Pick type C fibroblasts 25--38-fold and that of normal cells 3-fold. 5) The activating factor had an isoelectric point of 4.0 and an apparent molecular weight, as estimated by gel filtration, of 25000. Treatment with pronase E abolished its activity.

1)

    Qualitative lipid analyses by thin-layer chromatography
    PARACLINICAL

 of 4

    Niemann-Pick type C spleens
    MICROSCOPIC

 confirmed

    sphingomyelin accumulation
    MICROSCOPIC

 together with

    increase in the amount of glucocerebroside
    MICROSCOPIC

. 2) In the presence of

    crude sodium taurocholate
    MEDICATION

 as detergent,

    sphingomyelin degradation
    BIOCHEMICAL

 rates of normal and

    Niemann-Pick type C-cultured fibroblasts
    MICROSCOPIC

 were fairly close under standard conditions at pH 5.0. In the absence of

    sodium taurocholate
    NEG_FINDINGS

,

    sphingomyelinase activity
    BIOCHEMICAL

 was optimal at pH 4.0.

    Sphingomyelinase activities
    BIOCHEMICAL

 of fibroblasts from two patients with

    Niemann-Pick disease type C
    DIAGNOSIS

 measured

    without detergent
    NEG_FINDINGS

, were about

    30% of that
    BIOCHEMICAL

 of controls. 3)

    Extracts from Gaucher spleen heated to 90 degrees C
    MICROSCOPIC

 and

    devoid of sphingomyelinase activity
    NEG_FINDINGS

 stimulated at the optimal pH of 4.0

    sphingomyelin degradation by cultured normal fibroblasts (2--4-fold
    MICROSCOPIC

,

    Niemann-Pick type C fibroblasts
    MICROSCOPIC

 (5--9-fold), whereas similarly treated extracts from

    Niemann-Pick type C spleen showed no stimulation of sphingomyelin catabolism
    NEG_FINDINGS

.

    Heated extracts from normal human spleen
    MICROSCOPIC

 exhibited a smaller stimulation than that shown by

    Gaucher spleen
    MICROSCOPIC

. This

    stimulating effect could not be observed in fibroblasts from patients suffering from Niemann-Pick type B (sphingomyelinase defect)
    NEG_FINDINGS

. 4)

    Heat-treated extracts of Gaucher spleen
    MICROSCOPIC

 were fractionated by

    ion exchange chromatography
    PARACLINICAL

,

    isoelectric focusing
    PARACLINICAL

 and

    gel filtration
    PARACLINICAL

. The active fractions obtained by these procedures

    stimulated sphingomyelin as well as glucocerebroside degradation
    BIOCHEMICAL

 and were

    absent from the corresponding Niemann-Pick type C preparations
    NEG_FINDINGS

.

    Enriched activator preparations of Gaucher spleen
    MICROSCOPIC

 stimulated

    sphingomyelinase activity of Niemann-Pick type C fibroblasts
    BIOCHEMICAL

    25--38-fold
    BIOCHEMICAL

 and that of normal cells 3-fold. 5) The activating factor had an isoelectric point of 4.0 and an apparent molecular weight, as estimated by

    gel filtration
    PARACLINICAL

, of 25000. Treatment with

    pronase E abolished its activity
    NEG_FINDINGS

.


Partial splenectomy in Gaucher's disease.

An 11-year-old boy with Gaucher's disease is described. He had giant splenomegaly with severe signs of hypersplenism. A partial splenectomy was performed. On an isotope scan at follow-up, the remaining spleen was functioning well. Normal levels of IgM were recorded and there were no signs of hypersplenism.

An

    11-year-old
    AGE

    boy
    GENDER

 with

    Gaucher's disease
    DIAGNOSIS

 is described.

    He
    GENDER

 had

    giant splenomegaly
    SYMPTOMS

 with

    severe signs of hypersplenism
    SYMPTOMS

. A

    partial splenectomy
    MEDICATION

 was performed. On an

    isotope scan at follow-up
    PARACLINICAL

,

    the remaining spleen was functioning well
    SYMPTOMS

.

    Normal levels of IgM were recorded
    NEG_FINDINGS

 and there were

    no signs of hypersplenism
    NEG_FINDINGS

.

Normal levels of IgM were recorded
no signs of hypersplenism


Coexistence of IgA myeloma and Gaucher's disease.

An elderly woman of Ashkenazic Jewish descent, who had had adult Gaucher's disease diagnosed seven years previously, was found to have IgA myeloma. The diagnosis of IgA myeloma was confirmed by the presence of lytic lesions in the skull and long bones, atypical plasma cells in bone marrow, and monoclonal elevation of IgA, kappa-type. In addition, the marrow contained Gaucher's cells. A causal relationship between these two pathologic entities remains speculative.

An

    elderly
    AGE

    woman
    GENDER

 of

    Ashkenazic Jewish descent
    ETHNICITY

, who had had

    adult Gaucher's disease
    DIAGNOSIS

 diagnosed seven years previously, was found to have

    IgA myeloma
    DIAGNOSIS

. The diagnosis of

    IgA myeloma
    DIAGNOSIS

 was confirmed by the presence of

    lytic lesions in the skull and long bones
    SYMPTOMS

,

    atypical plasma cells in bone marrow
    MICROSCOPIC

, and

    monoclonal elevation of IgA, kappa-type
    BIOCHEMICAL

. In addition,

    the marrow contained Gaucher's cells
    MICROSCOPIC

. A causal relationship between these two pathologic entities remains speculative.

adult Gaucher's disease
IgA myeloma
IgA myeloma


Gaucher's disease associated with Hodgkin's disease.

A patient with chronic adult-onset Gaucher's disease is described. The diagnosis was based on the finding of typical Gaucher cells in the spleen, liver and bone marrow associated with deficiency of glucocerebrosidase. The patient also had Hodgkin's disease, nodular sclerosis type, stage III. The patient is alive and relatively well six years after presentation, having been treated with a combination of chemotherapeutic regimens. Previously reported cases of Gaucher's disease concurrent with Hodgkin's disease are reviewed.

A patient with

    chronic adult-onset Gaucher's disease
    DIAGNOSIS

 is described. The diagnosis was based on the finding of

    typical Gaucher cells in the spleen, liver and bone marrow
    MICROSCOPIC

 associated with

    deficiency of glucocerebrosidase
    BIOCHEMICAL

. The patient also had

    Hodgkin's disease, nodular sclerosis type, stage III
    DIAGNOSIS

. The patient is alive and relatively well six years after presentation, having been treated with a

    combination of chemotherapeutic regimens
    MEDICATION

. Previously reported cases of

    Gaucher's disease concurrent with Hodgkin's disease
    DIAGNOSIS

 are reviewed.


Gaucher's disease: a clinical, morphological and biochemical study of a Nigerian family.

Two Nigerian sibling presented with progressive hepato-splenomegaly in infancy from which they subsequently died. Morphological investigations carried out showed that the children had Gaucher's disease. Leucocyte B-glucocerebrosidase activities from the parents of the two siblings and also from one surviving sibling were found to be only about 50% of the enzyme activities in control subjects while hexosaminidase and B-glucuronidase activities were within normal limits. There results showed that the three surviving relatives are heterozygotes and also provided a strong supporting evidence that the deceased children had Gaucher's disease. The occurence of this disease in African children living in Kenya, Uganda, the Congo and Nigeria, and in Black Americans suggest that this biochemical abnormality is not as rare in the Negroid race as has been believed hitherto, and may be widespread on the African continent.

Two

    Nigerian
    ETHNICITY

    sibling
    FAMILY

 presented with

    progressive hepato-splenomegaly
    SYMPTOMS

 in

    infancy
    AGE

 from which they subsequently

    died
    SYMPTOMS

.

    Morphological investigations
    PARACLINICAL

 carried out showed that the

    children
    AGE

 had

    Gaucher's disease
    DIAGNOSIS

.

    Leucocyte B-glucocerebrosidase activities from the parents of the two siblings and also from one surviving sibling were found to be only about 50% of the enzyme activities in control subjects
    BIOCHEMICAL

 while

    hexosaminidase and B-glucuronidase activities were within normal limits
    NEG_FINDINGS

. There results showed that

    the three surviving relatives are heterozygotes
    FAMILY

 and also provided a strong supporting evidence that the deceased children had

    Gaucher's disease
    DIAGNOSIS

. The occurence of this disease in

    African children
    ETHNICITY

 living in

    Kenya
    ETHNICITY

,

    Uganda
    ETHNICITY

, the

    Congo
    ETHNICITY

 and

    Nigeria
    ETHNICITY

, and in

    Black Americans
    ETHNICITY

 suggest that this

    biochemical abnormality
    DIAGNOSIS

 is not as rare in the

    Negroid race
    ETHNICITY

 as has been believed hitherto, and may be widespread on the African continent.

Nigerian
African children
Kenya
Uganda
Congo
Nigeria
Black Americans
Negroid race

Gaucher's disease
Gaucher's disease
biochemical abnormality


Neurologic complications of Gaucher's disease, type 3.

We discuss the clinical features of two patients with type 3 Gaucher's disease. Glucocerebroside levels in liver biopsy specimens were measured in both patients and the findings are discussed in regard to the pathogenesis of the disease.

We discuss the clinical features of two patients with

    type 3 Gaucher's disease
    DIAGNOSIS

.

    Glucocerebroside levels in liver biopsy specimens
    BIOCHEMICAL

 were measured in both patients and the findings are discussed in regard to the pathogenesis of the disease.


Neuropathic type of Gaucher's disease in a Mexican boy. Electron microscopy studies and considerations on the current concept of this disease.

Case report of a 32 month old boy with Gaucher's disease. He had an evolution of 22 months with neurological symptoms. The spleen was removed and was studied with light and electron microscopy. The study disclosed the typical morphological features of Gaucher's cells. A correlation was established between symptomatology, radiological findings and anatomic alterations in post mortem studies. An interesting fact is the absence of the disease in other family members and therefore this case may represent an example of a recent mutation. General considerations on the current concept of this disease are also discussed.

Case report of a

    32 month old
    AGE

    boy
    GENDER

 with

    Gaucher's disease
    DIAGNOSIS

.

    He
    GENDER

 had an

    evolution of 22 months
    AGE

 with

    neurological symptoms
    SYMPTOMS

. The

    spleen was removed
    PARACLINICAL

 and was studied with

    light and electron microscopy
    PARACLINICAL

. The study disclosed the

    typical morphological features of Gaucher's cells
    MICROSCOPIC

. A correlation was established between symptomatology, radiological findings and

    anatomic alterations
    SYMPTOMS

 in

    post mortem studies
    PARACLINICAL

. An interesting fact is the

    absence of the disease in other family members
    FAMILY

 and therefore this case may represent an example of a recent mutation. General considerations on the current concept of this disease are also discussed.

neurological symptoms
anatomic alterations


Central nervous system involvement in adult-onset Gaucher's disease.

Neuropathological findings are reported in an adult with Gaucher's disease. In this patient, Gaucher cells with characteristic storage material were found throughout the brain and also in the leptomeninges. They were confined to the perivascular space of small blood vessels and were commonly associated with intense perivascular, glio-mesodermal fibrillary reaction. Neuronal storage was not seen. Glucosylceramidase activities were severely deficient in both brain and liver and glucosylceramide was abnormally increased in the liver of this patient. The significance of the neuropathological changes is briefly discussed.

    Neuropathological findings
    SYMPTOMS

 are reported in an

    adult
    AGE

 with

    Gaucher's disease
    DIAGNOSIS

. In this patient,

    Gaucher cells with characteristic storage material were found throughout the brain and also in the leptomeninges
    MICROSCOPIC

.

    They were confined to the perivascular space of small blood vessels
    MICROSCOPIC

 and were commonly associated with

    intense perivascular, glio-mesodermal fibrillary reaction
    MICROSCOPIC

.

    Neuronal storage was not seen
    NEG_FINDINGS

.

    Glucosylceramidase activities were severely deficient in both brain and liver
    BIOCHEMICAL

 and

    glucosylceramide was abnormally increased in the liver
    MICROSCOPIC

 of this patient. The significance of the

    neuropathological changes
    SYMPTOMS

 is briefly discussed.

Neuropathological findings
neuropathological changes


Non-neuropathic Gaucher disease presenting in infancy.

The non-neuropathic form of Gaucher's disease was diagnosed in 11 children of non-Jewish ancestry in South Africa; all were under the age of 4. None had any neurological involvement and, apart from the precocious presentation and rapid course, the features in each resembled those of the classical 'adult' or chronic non-neuropathic form of Gaucher disease. By contrast, the condition presented after puberty in 24 out of 28 Ashkenazi Jews who were studied during the same investigation. Activity of beta-glucosidase was defective in both groups of patients and they could not be distinguished by histological criteria. Only one child with the infantile neuropathic form of Gaucher disease was identified during the survey. The preponderance of the atypical non-neuropathic form of the disorder in young children is of practical importance from the point of view of differential diagnosis in any child with hepatosplenomegaly.

The

    non-neuropathic form of Gaucher's disease
    DIAGNOSIS

 was diagnosed in 11

    children
    AGE

 of

    non-Jewish ancestry
    ETHNICITY

 in

    South Africa
    ETHNICITY

; all were

    under the age of 4
    AGE

.

    None had any neurological involvement
    NEG_FINDINGS

 and, apart from the

    precocious presentation
    SYMPTOMS

 and rapid course, the features in each resembled those of the classical

    'adult' or chronic non-neuropathic form of Gaucher disease
    DIAGNOSIS

. By contrast, the condition presented after

    puberty
    AGE

 in 24 out of 28

    Ashkenazi Jews
    ETHNICITY

 who were studied during the same investigation.

    Activity of beta-glucosidase was defective
    BIOCHEMICAL

 in both groups of patients and they

    could not be distinguished by histological criteria
    NEG_FINDINGS

. Only one

    child
    AGE

 with the

    infantile neuropathic form of Gaucher disease
    DIAGNOSIS

 was identified during the survey. The preponderance of the

    atypical non-neuropathic form of the disorder
    DIAGNOSIS

 in

    young children
    AGE

 is of practical importance from the point of view of

    differential diagnosis
    PARACLINICAL

 in any

    child
    AGE

 with

    hepatosplenomegaly
    SYMPTOMS

.

non-Jewish ancestry
South Africa
Ashkenazi Jews


Infantile Gaucher's disease.

This case report calls attention to the fact that infantile Gaucher's disease can occur in black infants. The infant's age, neurologic manifestations, and pathologic findings support the diagnosis.

This case report calls attention to the fact that

    infantile Gaucher's disease
    DIAGNOSIS

 can occur in

    black infants
    AGE

. The

    infant's age
    AGE

,

    neurologic manifestations
    SYMPTOMS

, and

    pathologic findings
    SYMPTOMS

 support the diagnosis.

neurologic manifestations
pathologic findings


Renal involvement in adult Gaucher's disease after splenectomy.

Gaucher's disease with severe clinical and pathologic renal involvement is exceptionally rare. This article describes severe renal involvement and proteinuria in a young black woman with Gaucher's disease. The accumulation of glucocerebroside (Gaucher bodies) in glomerular mesangial and endothelial cells and in interstitial cells of the kidney is indicative of the phagocytic potential and the deficiency of glucocerebroside-cleaving enzyme in these cells. Severe proteinuria in this patient was attributed to the extensive glomerular involvement by Gaucher's disease.

    Gaucher's disease
    DIAGNOSIS

 with

    severe clinical and pathologic renal involvement
    SYMPTOMS

 is exceptionally rare. This article describes

    severe renal involvement
    SYMPTOMS

 and

    proteinuria
    BIOCHEMICAL

 in a

    young
    AGE

    black
    ETHNICITY

    woman
    GENDER

 with

    Gaucher's disease
    DIAGNOSIS

. The

    accumulation of glucocerebroside (Gaucher bodies) in glomerular mesangial and endothelial cells and in interstitial cells of the kidney
    MICROSCOPIC

 is indicative of the

    phagocytic potential
    MICROSCOPIC

 and the

    deficiency of glucocerebroside-cleaving enzyme in these cells
    BIOCHEMICAL

.

    Severe proteinuria
    BIOCHEMICAL

 in this patient was attributed to the

    extensive glomerular involvement by Gaucher's disease
    MICROSCOPIC

.


Pseudo-Gaucher cells in multiple myeloma.

A bone biopsy specimen from a patient with multiple myeloma showed numerous Gaucher-like cells scattered throughout a homogeneous background of plasma cells. Further studies using histochemical stains, immunofluorescence, and light and electron microscopy were carried out to further define these cells. Light microscopy of Wright-stained and hematoxylin and eosin-stained marrow preparations showed large, round cells with fibrillar appearing cytoplasm and eccentric, pyknotic nuclei. These cells were periodic acid-Schiff positive, resistant to diastase digestion. Electron microscopy demonstrated plasma cells containing crystals in membrane-bound vesicles. Also, large macrophages among these plasma cells contained similar crystals surrounded by a single limiting membrane. Immunofluorescence staining of thin sections of marrow with fluorescein-labelled specific antiserums showed fluorescence of these large cells. Strong immunofluorescence was seen with polyvalent kappa and gamma antiserums but not with anti-albumin or serums with anti-lambda, mu or alpha specificity. It appears that these large cells have the light microscopic and histochemical characteristics of true Gaucher cells but, when studied with immunofluorescence and electron microscopy, it appears that the pseudo-Gaucher cells of multiple myeloma are bone marrow macrophages engorged with immunoglobulin.

A

    bone biopsy specimen
    PARACLINICAL

 from a patient with

    multiple myeloma
    DIAGNOSIS

 showed

    numerous Gaucher-like cells scattered throughout a homogeneous background of plasma cells
    MICROSCOPIC

. Further studies using

    histochemical stains
    PARACLINICAL

,

    immunofluorescence
    PARACLINICAL

, and

    light and electron microscopy
    PARACLINICAL

 were carried out to further define these cells.

    Light microscopy of Wright-stained and hematoxylin and eosin-stained marrow preparations
    PARACLINICAL

 showed

    large, round cells with fibrillar appearing cytoplasm and eccentric, pyknotic nuclei
    MICROSCOPIC

. These

    cells were periodic acid-Schiff positive
    MICROSCOPIC

,

    resistant to diastase digestion
    NEG_FINDINGS

.

    Electron microscopy
    PARACLINICAL

 demonstrated

    plasma cells containing crystals in membrane-bound vesicles
    MICROSCOPIC

. Also,

    large macrophages among these plasma cells contained similar crystals surrounded by a single limiting membrane
    MICROSCOPIC

.

    Immunofluorescence staining of thin sections of marrow with fluorescein-labelled specific antiserums
    PARACLINICAL

 showed

    fluorescence of these large cells
    MICROSCOPIC

.

    Strong immunofluorescence
    BIOCHEMICAL

 was seen with

    polyvalent kappa and gamma antiserums
    BIOCHEMICAL

 but

    not with anti-albumin or serums with anti-lambda, mu or alpha specificity
    NEG_FINDINGS

. It appears that these

    large cells
    MICROSCOPIC

 have the light

    microscopic and histochemical characteristics of true Gaucher cells
    SYMPTOMS

 but, when studied with

    immunofluorescence and electron microscopy
    PARACLINICAL

, it appears that the

    pseudo-Gaucher cells of multiple myeloma
    MICROSCOPIC

 are

    bone marrow macrophages engorged with immunoglobulin
    MICROSCOPIC

.

Strong immunofluorescence
polyvalent kappa and gamma antiserums


Acute leukaemia and Gaucher's disease.

As association between Gaucher's disease and haematopoietic neoplasias has been reported in only a few instances. The authors recently encountered 2 cases of adult Gaucher's disease that developed acute myelogenous/myelomonocytic leukaemia. Both individuals had a pre-leukaemic phase. These cases are reported.

As

    association between Gaucher's disease
    DIAGNOSIS

 and

    haematopoietic neoplasias
    DIAGNOSIS

 has been reported in only a few instances. The authors recently encountered 2 cases of

    adult
    AGE

    Gaucher's disease
    DIAGNOSIS

 that developed

    acute myelogenous/myelomonocytic leukaemia
    DIAGNOSIS

. Both individuals had a

    pre-leukaemic phase
    BIOCHEMICAL

. These cases are reported.


[Ankylosing spondylitis in monozygous twins. Study of HLA complex (author's transl)].

A study of HLA complex (HLA A, B, C, DRw, Bf, chiddo) in monozygous twins suffering from ankylosing spondylitis with different clinical courses. All the markers studied were identified. The results would tend to suggest that hereditary factors are not alone responsible in the course of ankylosing spondylitis. Furthermore, they are not the sole causative factor of the disease since the literature contains reports of discordant pairs of twins.

A study of

    HLA complex (HLA A, B, C, DRw, Bf, chiddo)
    GENETICS

 in

    monozygous twins
    FAMILY

 suffering from

    ankylosing spondylitis
    DIAGNOSIS

 with different clinical courses. All the markers studied were identified. The results would tend to suggest that

    hereditary factors
    GENETICS

 are not alone responsible in the course of

    ankylosing spondylitis
    DIAGNOSIS

. Furthermore, they are not the sole causative factor of the disease since the literature contains reports of

    discordant pairs of twins
    FAMILY

.

ankylosing spondylitis
ankylosing spondylitis


Attempt at enzyme replacement by organ transplantation: renal transplantation in Gaucher disease.

Following renal transplantation, hepatic glucocerebroside deposits in a child with Gaucher disease were reduced. This suggests that enzyme replacement had been achieved.

Following

    renal transplantation
    MEDICATION

,

    hepatic glucocerebroside deposits in
    MICROSCOPIC

 a

    child
    AGE

 with

    Gaucher disease were reduced
    MICROSCOPIC

. This suggests that

    enzyme replacement
    MEDICATION

 had been achieved.

renal transplantation
enzyme replacement


Exaggerated anterior vertebral notching.

Three children with marrow-packing disorders demonstrated exaggerated anterior vertebral notches with poorly defined cortical margins. One child had thalassemia major, another had Gaucher disease, and a third had metastatic neuroblastoma. A discussion of each case and the etiology of the notches is presented.

Three

    children
    AGE

 with

    marrow-packing disorders
    DIAGNOSIS

 demonstrated

    exaggerated anterior vertebral notches with poorly defined cortical margins
    SYMPTOMS

. One

    child
    AGE

 had

    thalassemia major
    DIAGNOSIS

, another had

    Gaucher disease
    DIAGNOSIS

, and a third had

    metastatic neuroblastoma
    DIAGNOSIS

. A discussion of each case and the etiology of the

    notches
    SYMPTOMS

 is presented.

marrow-packing disorders
thalassemia major
Gaucher disease
metastatic neuroblastoma


[Roentgenologic characteristics of Gaucher's disease (author's transl)].

Gaucher's disease is a rare metabolic disorder in which there is an abnormal accumulation of cerebrosides in the reticuloendothelial system due to a deficit of beta-glucuronidase. Three patients with this disease, 8, 14, and 23 years old, were studied. The purpose of this paper is to point out some of the roentgenologic findings, such as areas of femoral osteolysis, renal venous thrombosis, and in one patient, sclerosis of the sacroiliac joint. Splenomegaly and alteration of the tubular bony structure of the distal end of the femur were present in all three cases. The roentgenologic images of the disease are discussed. The osteoarticular system is the most often affected. Osteolysis is the basic lesion with expansion of the bone marrow and sclerosis. The earliest symptom and sometimes the only one is the Erlenmeyer flask deformity or widening of the distal portion of the femur. Sometimes there is a high degree of deossification without definite osteolytic lesions. Pathologic fractures and fractures caused by pressure of the vertebral bodies are common. Aseptic femoral necrosis are often present. Other less frequent sites of osteoarticular pathology are the skull, jaws, ribs, and sacroiliac joints. Splenomegaly is the most frequent visceral lesion. Other organs sometimes affected are the liver, kidneys, heart, lymphatic system, and lungs, with nodular or basal reticular infiltrations.

    Gaucher's disease
    DIAGNOSIS

 is a

    rare metabolic disorder
    DIAGNOSIS

 in which there is an

    abnormal accumulation of cerebrosides in the reticuloendothelial system
    MICROSCOPIC

 due to a

    deficit of beta-glucuronidase
    BIOCHEMICAL

. Three patients with this disease,

    8, 14, and 23 years old
    AGE

, were studied. The purpose of this paper is to point out some of the roentgenologic findings, such as

    areas of femoral osteolysis
    SYMPTOMS

,

    renal venous thrombosis
    SYMPTOMS

, and in one patient,

    sclerosis of the sacroiliac joint
    SYMPTOMS

.

    Splenomegaly
    SYMPTOMS

 and

    alteration of the tubular bony structure of the distal end of the femur
    SYMPTOMS

 were present in all three cases. The

    roentgenologic images
    PARACLINICAL

 of the disease are discussed. The

    osteoarticular system
    SYMPTOMS

 is the most often affected.

    Osteolysis
    SYMPTOMS

 is the basic lesion with

    expansion of the bone marrow and sclerosis
    SYMPTOMS

. The earliest symptom and sometimes the only one is the

    Erlenmeyer flask deformity or widening of the distal portion of the femur
    SYMPTOMS

. Sometimes there is a

    high degree of deossification
    SYMPTOMS

    without definite osteolytic lesions
    NEG_FINDINGS

.

    Pathologic fractures and fractures caused by pressure of the vertebral bodies
    SYMPTOMS

 are common.

    Aseptic femoral necrosis
    SYMPTOMS

 are often present. Other less frequent sites of

    osteoarticular pathology
    SYMPTOMS

    are the skull, jaws, ribs, and sacroiliac joints
    SYMPTOMS

.

    Splenomegaly
    SYMPTOMS

 is the most frequent

    visceral lesion
    SYMPTOMS

. Other organs sometimes affected

    are the liver, kidneys, heart, lymphatic system, and lungs
    SYMPTOMS

, with

    nodular or basal reticular infiltrations
    MICROSCOPIC

.

Gaucher's disease
rare metabolic disorder


Familial psychosis and diverse neurologic abnormalities in adult-onset Gaucher's disease.

A family is described in which adult-onset Gaucher's disease developed, followed years later by atypical psychotic disorders with neurologic and electroencephalographic abnormalities. A biochemical investigation of primary and secondary enzyme alterations in the index case was performed in an attempt to identify a pattern that might be specific to this clinical profile. The literature pertaining to CNS involvement in adult patients with Gaucher's disease is also reviewed. An etiologic link may exist between the inherited metabolic disorder and associated neuropsychiatric impairment. The biochemical basis of this hypothesized association remains unclear, however, and further enzymatic and pathologic investigations are warranted.

A family is described in which

    adult-onset Gaucher's disease
    DIAGNOSIS

 developed, followed years later by

    atypical psychotic disorders
    SYMPTOMS

 with

    neurologic and electroencephalographic abnormalities
    SYMPTOMS

. A

    biochemical investigation of primary and secondary enzyme alterations
    PARACLINICAL

 in the index case was performed in an attempt to identify a pattern that might be specific to this clinical profile. The literature pertaining to

    CNS involvement
    SYMPTOMS

 in

    adult
    AGE

 patients with

    Gaucher's disease
    DIAGNOSIS

 is also reviewed. An etiologic link may exist between the

    inherited metabolic disorder
    GENETICS

 and associated

    neuropsychiatric impairment
    SYMPTOMS

. The biochemical basis of this hypothesized association remains unclear, however, and further

    enzymatic and pathologic investigations
    PARACLINICAL

 are warranted.

adult-onset Gaucher's disease
Gaucher's disease


Nonsecretory IgD-kappa multiple myeloma in a patient with Gaucher's disease.

A patient with Gaucher's disease and non-secretory multiple myeloma is described. The presence of typical Gaucher and myeloma cells was confirmed by transmission and scanning electron microscopy. The immunological studies established the diagnosis of 'non-secretory' type of multiple myeloma.

A patient with

    Gaucher's disease
    DIAGNOSIS

 and

    non-secretory multiple myeloma
    DIAGNOSIS

 is described. The

    presence of typical Gaucher and myeloma cells
    MICROSCOPIC

 was confirmed by

    transmission and scanning electron microscopy
    PARACLINICAL

. The

    immunological studies
    PARACLINICAL

 established the diagnosis of

    'non-secretory' type of multiple myeloma
    MICROSCOPIC

.

Gaucher's disease
non-secretory multiple myeloma


Radionuclide assessment of Gaucher's disease.

Gaucher's disease involves multiple organs and may present with variable severity. The scintigraphic appearance of the reticuloendothelial system and bone are described in three patient's with Gaucher's disease. Scintigraphic abnormalities reflected the severity of organ involvement and correlated well with the patients' clinical status. Scintigraphy appears useful for the evaluation and followup of patients with Gaucher's disease.

    Gaucher's disease
    DIAGNOSIS

 involves

    multiple organs
    SYMPTOMS

 and may present with variable severity. The

    scintigraphic appearance of the reticuloendothelial system and bone
    PARACLINICAL

 are described in three patient's with

    Gaucher's disease
    DIAGNOSIS

.

    Scintigraphic abnormalities
    SYMPTOMS

 reflected the severity of

    organ involvement
    SYMPTOMS

 and correlated well with the patients' clinical status.

    Scintigraphy
    PARACLINICAL

 appears useful for the evaluation and followup of patients with

    Gaucher's disease
    DIAGNOSIS

.

Gaucher's disease
Gaucher's disease
Gaucher's disease

multiple organs
Scintigraphic abnormalities
organ involvement


Primary amyloidosis associated with Gaucher's disease.

Elevations in serum immunoglobulins, frequently monoclonal in nature, are known to occur in patients with the adult form of Gaucher's disease. We describe amyloidosis in a 46-year-old woman of Italian ancestry with Gaucher's disease, who also had 3100 mg/dl of monoclonal IgA. She died of restrictive cardiac disease. A 50-year-old sister, also with Gaucher's disease, had 1300 mg/dl of polyclonal IgM but no evidence of amyloidosis. A glucosyl sphingosine-Sepharose affinity column provided no evidence that the large amount of immunoglobulin present has specific affinity for glucosyl ceramide. This, to our knowledge, is the first report of amyloidosis complicating Gaucher's disease.

    Elevations in serum immunoglobulins
    BIOCHEMICAL

, frequently

    monoclonal in nature
    BIOCHEMICAL

, are known to occur in patients with the

    adult form of Gaucher's disease
    DIAGNOSIS

. We describe

    amyloidosis
    DIAGNOSIS

 in a

    46-year-old
    AGE

    woman
    GENDER

 of

    Italian ancestry
    ETHNICITY

 with

    Gaucher's disease
    DIAGNOSIS

, who also had 3100 mg/dl of monoclonal IgA.

    She
    GENDER

    died
    SYMPTOMS

 of

    restrictive cardiac disease
    DIAGNOSIS

. A

    50-year-old
    AGE

    sister, also with Gaucher's disease
    FAMILY

, had

    1300 mg/dl of polyclonal IgM
    BIOCHEMICAL

 but

    no evidence of amyloidosis
    NEG_FINDINGS

. A

    glucosyl sphingosine-Sepharose affinity column
    PARACLINICAL

 provided

    no evidence that
    NEG_FINDINGS

 the

    large amount of immunoglobulin present has specific affinity for glucosyl ceramide
    BIOCHEMICAL

. This, to our knowledge, is the first report of

    amyloidosis
    DIAGNOSIS

    complicating Gaucher's disease
    DIAGNOSIS

.

adult form of Gaucher's disease
amyloidosis
Gaucher's disease
restrictive cardiac disease
amyloidosis
complicating Gaucher's disease

no evidence of amyloidosis
no evidence that


[Infantile form of Gaucher's disease. Clinical and biological studies in 1 case. Prenatal diagnosis in 2 further normal pregnancies].

A clinical report of a typical case of infantile Gaucher's disease is given. Study of the beta-glucosidase activity in leukocytes and skin fibroblasts confirmed the diagnosis in the patient and established the heterozygote condition of the parents. Two later pregnancies have been monitored by enzymatic study of cultured amniotic fluid cells. Both foetuses were predicted to be healthy, which was confirmed after birth. The report includes a histopathological ultrastructural, chemical and enzymatic study of liver, spleen and brain obtained at autopsy. Possible clues to the physiopathological mechanism of the cerebral lesion are discussed.

A clinical report of a typical case of

    infantile Gaucher's disease
    DIAGNOSIS

 is given.

    Study of the beta-glucosidase activity in leukocytes and skin fibroblasts
    PARACLINICAL

 confirmed the diagnosis in the patient and established the

    heterozygote condition of the parents
    FAMILY

. Two later pregnancies have been monitored by

    enzymatic study of cultured amniotic fluid cells
    PARACLINICAL

.

    Both foetuses were predicted to be healthy
    FAMILY

, which was confirmed after

    birth
    AGE

. The report includes a

    histopathological ultrastructural, chemical and enzymatic study of liver, spleen and brain
    PARACLINICAL

 obtained at

    autopsy
    PARACLINICAL

. Possible clues to the physiopathological mechanism of the

    cerebral lesion
    SYMPTOMS

 are discussed.


Pitfalls in the use of artificial substrates for the diagnosis of Gaucher's disease.

A patient with Gaucher's disease is described, in whom the disease could not be diagnosed enzymically in liver and leucocytes using artificial substrate 4-methylumbelliferyl beta-glucoside. Normal activity was found in the liver, and about 60% of control activity was determined in the patient's leucocytes. In contrast, when [14C]-N-stearoyl glucocerebroside was employed as a substrate, activity as low as 5% of control has been found in all the proband's tissues, and carrier levels were determined in the proband's parents and maternal uncle.

A patient with

    Gaucher's disease
    DIAGNOSIS

 is described, in whom the

    disease could not be diagnosed enzymically in liver and leucocytes
    NEG_FINDINGS

 using artificial substrate

    4-methylumbelliferyl beta-glucoside
    PARACLINICAL

.

    Normal activity was found in the liver
    NEG_FINDINGS

, and

    about 60% of control activity was determined in the patient's leucocytes
    BIOCHEMICAL

. In contrast, when

    [14C]-N-stearoyl glucocerebroside
    MICROSCOPIC

 was employed as a substrate,

    activity as low as 5% of control has been found in all the proband's tissues
    BIOCHEMICAL

, and

    carrier levels were determined in the proband's parents and maternal uncle
    FAMILY

.


[Report of a case of Gaucher's disease in adult].

The authors report a case of Gaucher's disease in an adult. This is a rare disease due to the accumulation of a glucoceramide in the reticulo-endothelial cells and may remain for long clinically symptomless, as in this case. The diagnosis suggested by the biological disturbance, viz. moderate thrombopenia, hypergammaglobulinemia, increase in SGPT, was conformed by the presence of Gaucher's cells in the liver and in the bone marrow, and by the existence of an intraleukocytic glucosidase deficiency. The authors recall the clinical forms of this disease, and recent clinical trials.

The authors report a case of

    Gaucher's disease
    DIAGNOSIS

 in an

    adult
    AGE

. This is a rare disease due to the

    accumulation of a glucoceramide in the reticulo-endothelial cells
    MICROSCOPIC

 and may

    remain for long clinically symptomless
    NEG_FINDINGS

, as in this case. The diagnosis suggested by the biological disturbance, viz.

    moderate thrombopenia
    BIOCHEMICAL

,

    hypergammaglobulinemia
    BIOCHEMICAL

,

    increase in SGPT
    BIOCHEMICAL

, was conformed by the

    presence of Gaucher's cells in the liver and in the bone marrow
    MICROSCOPIC

, and by the existence of an

    intraleukocytic glucosidase deficiency
    BIOCHEMICAL

. The authors recall the clinical forms of this disease, and recent clinical trials.

moderate thrombopenia
hypergammaglobulinemia
increase in SGPT
intraleukocytic glucosidase deficiency


Amyloidosis. An unusual complication of Gaucher's disease.

Gaucher's disease has been associated with plasma cell dyscrasias. A patient had Gaucher's disease, nephrotic syndrome, and systemic amyloidosis. Plasmacytosis in the bone marrow, the presence of light chains in the urine and renal glomeruli, and the finding of low circulating immunoglobulin levels suggest that the amyloid in this patient is related to a plasma cell dyscrasia.

    Gaucher's disease
    DIAGNOSIS

 has been associated with

    plasma cell dyscrasias
    MICROSCOPIC

. A patient had

    Gaucher's disease
    DIAGNOSIS

,

    nephrotic syndrome
    DIAGNOSIS

, and

    systemic amyloidosis
    DIAGNOSIS

.

    Plasmacytosis in the bone marrow
    MICROSCOPIC

, the

    presence of light chains in the urine and renal glomeruli
    MICROSCOPIC

, and the finding of

    low circulating immunoglobulin levels
    BIOCHEMICAL

 suggest that the

    amyloid
    DIAGNOSIS

 in this patient is related to a

    plasma cell dyscrasia
    DIAGNOSIS

.

Gaucher's disease
Gaucher's disease
nephrotic syndrome
systemic amyloidosis
amyloid
plasma cell dyscrasia


Unusual cardiac, renal and pulmonary involvement in Gaucher's disease. Intersitial glucocerebroside accumulation, pulmonary hypertension and fatal bone marrow embolization.

A 25 year old black woman who had manifestations of Gaucher's disease since one year of age is described. This patient had clinically significant cardiac, renal and pulmonary involvement with Gaucher's disease. Interstitial infiltration of the myocardium by Gaucher cells caused decreased left ventricular compliance and decreased cardiac output. In the kidney, Gaucher cells were present in the mesangium of the glomeruli and the interstitium of the cortex. Also, electron dense, intramembranous granular deposits were seen in glomeruli on electron microscopy. The pulmonary findings included pulmonary arterial hypertension, accentuated basilar deposition of glucocerebroside in the interstitium of alveolar septums and fatal bone marrow embolization.

A

    25 year old
    AGE

    black
    ETHNICITY

    woman
    GENDER

 who had manifestations of

    Gaucher's disease
    DIAGNOSIS

    since one year of age
    AGE

 is described. This patient had

    clinically significant cardiac, renal and pulmonary involvement
    SYMPTOMS

 with

    Gaucher's disease
    DIAGNOSIS

.

    Interstitial infiltration of the myocardium by Gaucher cells
    MICROSCOPIC

 caused

    decreased left ventricular compliance
    SYMPTOMS

 and

    decreased cardiac output
    SYMPTOMS

.

    In the kidney
    MICROSCOPIC

,

    Gaucher cells were present in the mesangium of the glomeruli and the interstitium of the cortex
    MICROSCOPIC

. Also,

    electron dense, intramembranous granular deposits were seen in glomeruli
    MICROSCOPIC

 on

    electron microscopy
    PARACLINICAL

. The

    pulmonary findings
    SYMPTOMS

 included

    pulmonary arterial hypertension
    SYMPTOMS

,

    accentuated basilar deposition of glucocerebroside in the interstitium of alveolar septums
    MICROSCOPIC

 and

    fatal bone marrow embolization
    SYMPTOMS

.


Immune deficiency, thrombocytopenia and osteomyelitis in pediatric patients.

Surgical decompression of osteomyelitis in pediatric patients should be an essential part of therapy in most cases. The initial deferral of prompt decompression in two patients because of underlying chronic, hemorrhagic (thrombocytopenic) disorders-one with Wiskott-Aldrich syndrome and one with Gaucher's disease-resulted in more serious and prolonged courses of the infectious processes. The complications might have been ameliorated by earlier drainage in each case. Based upon the experience gained from these two patients, we recommend early drainage, with appropriate treatment of the hemorrhagic disorder, to prevent more widespread dissemination or prolongation of osseous infection in similarly affected children.

    Surgical decompression of osteomyelitis
    MEDICATION

 in

    pediatric
    AGE

 patients should be an essential part of therapy in most cases. The initial

    deferral of prompt decompression
    NEG_FINDINGS

 in two patients because of underlying

    chronic, hemorrhagic (thrombocytopenic) disorders
    DIAGNOSIS

-one with

    Wiskott-Aldrich syndrome
    DIAGNOSIS

 and one with

    Gaucher's disease
    DIAGNOSIS

-resulted in

    more serious and prolonged courses of the infectious processes
    SYMPTOMS

. The complications might have been ameliorated by

    earlier drainage
    MEDICATION

 in each case. Based upon the experience gained from these two patients, we recommend

    early drainage
    MEDICATION

, with appropriate treatment of the

    hemorrhagic disorder
    DIAGNOSIS

, to prevent

    more widespread dissemination or prolongation of osseous infection
    SYMPTOMS

 in similarly affected

    children
    AGE

.

Surgical decompression of osteomyelitis
earlier drainage
early drainage


[Lipid thesaurismosis rheumatism. Joint manifestation during glucocerebrosidase deficiency (Gaucher's disease). Ultrastructural study of the synovial membrane].

Articular inflammatory involvement may be the first sign of gluocecerebrosidase deficiency (Gaucher's disease). Electron microscope study shows specific synovial storage lesions which explain arthritic manifestations. Furthermore presence of mitochondrial microcrystals, (apatite?), suggest microcrystal pathogenesis of Gaucher's arthritis.

    Articular inflammatory involvement
    SYMPTOMS

 may be the first sign of

    gluocecerebrosidase deficiency
    BIOCHEMICAL

 (

    Gaucher's disease)
    DIAGNOSIS

.

    Electron microscope study
    PARACLINICAL

 shows

    specific synovial storage lesions
    MICROSCOPIC

 which explain

    arthritic manifestations
    SYMPTOMS

. Furthermore

    presence of mitochondrial microcrystals, (apatite?)
    MICROSCOPIC

, suggest

    microcrystal pathogenesis
    MICROSCOPIC

 of

    Gaucher's arthritis
    DIAGNOSIS

.

Articular inflammatory involvement
arthritic manifestations


[Gaucher's disease. Morphological study of lymph nodes by electron microscopy].

The morphological study of lymph node biopsies by light and electron microscopes is reported. The patient was a 7 months old infant with Gaucher's disease and infection symptoms of upper respiratory ducts. We believe this to be a case of lesser affection, since the patient was admitted complaining of complications that gave way to medical treatment. Lymphadenopathy and moderate liver and splenomegaly were occasional findings during examination. Through the light microscope, Gaucher's cells showed an eccentric nucleous, cytoplasmic striae which, at the electron microscope showed to be tubular bodies.

The

    morphological study of lymph node biopsies
    PARACLINICAL

 by

    light and electron microscopes
    PARACLINICAL

 is reported. The patient was a

    7 months old
    AGE

    infant
    AGE

 with

    Gaucher's disease
    DIAGNOSIS

 and

    infection symptoms of upper respiratory ducts
    SYMPTOMS

. We believe this to be a case of lesser affection, since the patient was admitted complaining of

    complications
    SYMPTOMS

 that gave way to medical treatment.

    Lymphadenopathy
    SYMPTOMS

 and

    moderate liver
    SYMPTOMS

 and

    splenomegaly
    SYMPTOMS

 were occasional findings during examination. Through the

    light microscope
    PARACLINICAL

,

    Gaucher's cells showed an eccentric nucleous, cytoplasmic striae
    MICROSCOPIC

 which, at the

    electron microscope
    PARACLINICAL

 showed to

    be tubular bodies
    MICROSCOPIC

.


Gaucher's disease and pregnancy.

Two patients with Gaucher's disease during pregnancy are reported. In one there were severe puerperal hemorrhagic complications attributable to thrombocytopenia secondary to infiltration of the reticuloendothelial system by Gaucher cells. The conclusion as reported in previous literature, which is reviewed, regarding the absence of hemorrhagic complications is disputed since on of the cases reported here showed that these may be severe and occur late in the puerperium.

Two patients with

    Gaucher's disease
    DIAGNOSIS

 during

    pregnancy
    DIAGNOSIS

 are reported. In one there were

    severe puerperal hemorrhagic complications
    SYMPTOMS

 attributable to

    thrombocytopenia
    BIOCHEMICAL

 secondary to

    infiltration of the reticuloendothelial system by Gaucher cells
    MICROSCOPIC

. The conclusion as reported in previous literature, which is reviewed, regarding the

    absence of hemorrhagic complications
    NEG_FINDINGS

 is disputed since on of the cases reported here showed that these may be severe and occur

    late in the puerperium
    AGE

.


Multiple glycosidase deficiencies in a case of juvenile (type 3) Gaucher disease.

Biochemical investigations were performed on autopsy tissues obtained from an 11-year-old girl who died with the juvenile, subacute neuropathic form of Gaucher disease. In addition to the expected deficiency of glucocerebrosidase activity, extracts of both liver and kidney from this individual displayed a profound (greater than or equal to 90%) deficiency of "soluble" beta-glucosidase, beta-xylosidase, and beta-galactosidase activities. Fibroblasts obtained from this individual also contained markedly reduced levels of beta-xylosidase activity but normal levels of beta-D-fucosidase and beta-galactosidase activity. Because the soluble beta-glucosidase, beta-xylosidase, and a portion of the beta-galactosidase activities from control human liver all cochromatographed on a gel filtration column of Sephadex G-200, it is suggested that these activities all reside in a single enzyme, analogous to the situation described in a number of nonhuman, mammalian tissues. This demonstration of multiple glycosidase deficiencies in addition to the deficiency of glucocerebrosidase in a case of subacute neuropathic Gaucher disease suggests that other biochemical aberrations, in addition to a deficiency of glucocerebrosidase, might contribute to pathology in some cases of Gaucher disease.

    Biochemical investigations
    PARACLINICAL

 were performed on

    autopsy tissues
    PARACLINICAL

 obtained from an

    11-year-old
    AGE

    girl
    GENDER

 who

    died
    SYMPTOMS

 with the

    juvenile, subacute neuropathic form of Gaucher disease
    DIAGNOSIS

. In addition to the expected

    deficiency of glucocerebrosidase activity
    BIOCHEMICAL

,

    extracts of both liver and kidney
    MICROSCOPIC

 from this individual displayed a

    profound (greater than or equal to 90%) deficiency of "soluble" beta-glucosidase, beta-xylosidase, and beta-galactosidase activities
    BIOCHEMICAL

.

    Fibroblasts
    MICROSCOPIC

 obtained from this individual also contained

    markedly reduced levels of beta-xylosidase activity
    BIOCHEMICAL

 but

    normal levels of beta-D-fucosidase and beta-galactosidase activity
    NEG_FINDINGS

. Because the

    soluble beta-glucosidase, beta-xylosidase, and a portion of the beta-galactosidase activities from control human liver all cochromatographed
    BIOCHEMICAL

 on a

    gel filtration column of Sephadex G-200
    PARACLINICAL

, it is suggested that these activities all reside in a single enzyme, analogous to the situation described in a number of nonhuman, mammalian tissues. This demonstration of

    multiple glycosidase deficiencies
    BIOCHEMICAL

 in addition to the

    deficiency of glucocerebrosidase
    BIOCHEMICAL

 in a case of

    subacute neuropathic Gaucher disease
    DIAGNOSIS

 suggests that other biochemical aberrations, in addition to a

    deficiency of glucocerebrosidase
    BIOCHEMICAL

, might contribute to pathology in some cases of

    Gaucher disease
    DIAGNOSIS

.


Marked elevation of serum angiotension-converting enzyme and hepatic fibrosis containing long-spacing collagen fibrils in type 2 acute neuronopathic Gaucher's disease.

Serum angiotensin-converting enzyme in a patient with type 2 acute neuronopathic Gaucher's disease (242 nmol/min/ml) was 10.8 times higher than values for eight patients with other hereditary neurologic abnormalities (22.5 +/- 2.0) and 9.4 times higher than those for 12 patients with other diseases (25.7 +/- 2.6) (P less than 0.001). Serum lysozyme was not elevated in the patient with type 2 Gaucher's disease. These results indicate that elevated serum angiotensin-converting enzyme in an infant with neurologic involvement and hepatosplenomegaly is suggestive of the possibility of type 2 Gaucher's disease. Typical Gaucher's cells and fibrosis were observed by light and electron microscopy of the liver. An aspect hitherto unreported in Gaucher's disease or in the liver was that approximately 20% of the collagen fibrils were of the long-spacing type, with periodicity of 1,000 to 1,100 A and diameters of 900 to 1,500 A.

    Serum angiotensin-converting enzyme
    BIOCHEMICAL

 in a patient with

    type 2 acute neuronopathic Gaucher's disease
    DIAGNOSIS

    (242 nmol/min/ml) was 10.8 times higher
    BIOCHEMICAL

 than values for eight patients with other

    hereditary neurologic abnormalities
    NEG_FINDINGS

    (22.5 +/- 2.0)
    BIOCHEMICAL

 and 9.4 times higher than those for 12 patients with other diseases (

    25.7 +/- 2.6)
    BIOCHEMICAL

 (P less than 0.001).

    Serum lysozyme was not elevated
    NEG_FINDINGS

 in the patient with

    type 2 Gaucher's disease
    NEG_FINDINGS

. These results indicate that

    elevated serum angiotensin-converting enzyme
    BIOCHEMICAL

 in an

    infant
    AGE

 with

    neurologic involvement
    SYMPTOMS

 and

    hepatosplenomegaly
    SYMPTOMS

 is suggestive of the possibility of

    type 2 Gaucher's disease
    DIAGNOSIS

.

    Typical Gaucher's cells and fibrosis
    MICROSCOPIC

 were observed by

    light and electron microscopy of the liver
    PARACLINICAL

. An aspect hitherto unreported in

    Gaucher's disease
    MICROSCOPIC

 or in the liver was that

    approximately 20% of the collagen fibrils were of the long-spacing type, with periodicity of 1,000 to 1,100 A and diameters of 900 to 1,500 A.
    MICROSCOPIC

hereditary neurologic abnormalities
Serum lysozyme was not elevated
type 2 Gaucher's disease