Proximal humeral defects in Gaucher's disease.

Defects in the medial aspect of the proximal humeral metaphysis of two patients with Gaucher's disease are reported and their aetiology discussed. Similar cortical irregularities have been described as a normal variant in children and their presence in patients with an infiltrative disorder suggested as being coincidental. The two reported cases indicate that there is a causal association in Gaucher's disease since the defect persisted post-skeletal maturity in one case and progressed to bilateral pathological fractures of the proximal humeri in the other case. A review of the radiographs of 50 patients, pre-skeletal maturity, presenting with idiopathic scoliosis revealed a defect of the proximal humeral metaphysis in only one case, to give an estimated incidence of this anomaly in the "normal" population of 2%. It is suggested that the presence of this defect is non-specific with a spectrum of occurrence from the normal variant to the clearly pathological. The presence, however, of subtle abnormalities in the underlying bone tend to indicate a pathological entity.

    Defects in the medial aspect of the proximal humeral metaphysis
    SYMPTOMS

 of two patients with

    Gaucher's disease
    DIAGNOSIS

 are reported and their aetiology discussed. Similar

    cortical irregularities
    SYMPTOMS

 have been described as a normal variant in

    children
    AGE

 and their presence in patients with an

    infiltrative disorder
    DIAGNOSIS

 suggested as being coincidental. The two reported cases indicate that there is a causal association in

    Gaucher's disease
    DIAGNOSIS

 since the defect persisted

    post-skeletal maturity
    AGE

 in one case and progressed to

    bilateral pathological fractures of the proximal humeri
    SYMPTOMS

 in the other case. A review of the

    radiographs
    PARACLINICAL

 of 50 patients,

    pre-skeletal maturity
    AGE

, presenting with

    idiopathic scoliosis
    DIAGNOSIS

 revealed a

    defect of the proximal humeral metaphysis
    SYMPTOMS

 in only one case, to give an estimated incidence of this anomaly in the "normal" population of 2%. It is suggested that the presence of this defect is non-specific with a spectrum of occurrence from the normal variant to the clearly pathological. The presence, however, of

    subtle abnormalities in the underlying bone
    SYMPTOMS

 tend to indicate a pathological entity.

Gaucher's disease
infiltrative disorder
Gaucher's disease
idiopathic scoliosis


Scintigraphic and magnetic resonance studies in a patient with Gaucher's disease.

In-111 chloride imaging was used in the evaluation of a patient with Type I Gaucher's disease before splenectomy for pancytopenia. This case is the first report of its use in this clinical setting. The image demonstrated the presence of adequate marrow reserve, thereby suggesting that the pancytopenia was due to hypersplenism rather than marrow replacement. Normalization of blood counts after splenectomy confirmed this interpretation. Eight months later, the patient had acute pain in the left knee. Bone imaging suggested a left lateral tibial plateau fracture that was not seen on plain radiographs or magnetic resonance imaging, but was confirmed by x-ray tomography. The significance and implications of these findings are discussed.

    In-111 chloride imaging
    PARACLINICAL

 was used in the evaluation of a patient with

    Type I Gaucher's disease
    DIAGNOSIS

 before

    splenectomy
    MEDICATION

 for

    pancytopenia
    BIOCHEMICAL

. This case is the first report of its use in this clinical setting. The image demonstrated the

    presence of adequate marrow reserve
    MICROSCOPIC

, thereby suggesting that the

    pancytopenia
    BIOCHEMICAL

 was due to

    hypersplenism
    BIOCHEMICAL

 rather than

    marrow replacement
    BIOCHEMICAL

.

    Normalization of blood counts
    BIOCHEMICAL

 after

    splenectomy
    MEDICATION

 confirmed this interpretation. Eight months later, the patient had

    acute pain in the left knee
    SYMPTOMS

.

    Bone imaging
    PARACLINICAL

 suggested a

    left lateral tibial plateau fracture
    SYMPTOMS

 that

    was not seen on plain radiographs or magnetic resonance imaging
    NEG_FINDINGS

, but was confirmed by

    x-ray tomography
    PARACLINICAL

. The significance and implications of these findings are discussed.

pancytopenia
pancytopenia
hypersplenism
marrow replacement
Normalization of blood counts

acute pain in the left knee
left lateral tibial plateau fracture


Long-term follow-up of the first successful bone marrow transplantation in Gaucher disease.

A 9-year-old girl with juvenile Gaucher disease underwent splenectomy and allogeneic bone marrow transplantation. Her HLA-identical brother with normal cerebroside-beta-glucosidase activity served as donor. One month after transplantation, cerebroside-beta-glucosidase activity in the lymphocytes were normal. Plasma glucosylceramide normalized already after splenectomy and further decreased after marrow transplantation. Glucosylceramide in the erythrocytes was normal around a year after transplantation. The enlarged liver normalized in size by 2 years. Gaucher cells were still present in the bone marrow 1 year after transplantation but had completely disappeared at 3 years. The patient has grown 29 cm during the 5 years that have passed after transplantation compared to 1 cm/year during 3 years before. The patient has a slight obstructive ventilatory impairment, and chest deformities have appeared. Wechsler intelligence scale performance has slowly decreased after transplantation. This may be caused by continued neuronal storage of glucosylceramide. Otherwise, this patient is active and healthy 5 years after bone marrow transplantation.

A

    9-year-old
    AGE

    girl
    GENDER

 with

    juvenile Gaucher disease
    DIAGNOSIS

 underwent

    splenectomy
    MEDICATION

 and

    allogeneic bone marrow transplantation
    MEDICATION

.

    Her
    GENDER

    HLA-identical brother with normal cerebroside-beta-glucosidase activity
    FAMILY

 served as donor. One month after

    transplantation
    MEDICATION

,

    cerebroside-beta-glucosidase activity in the lymphocytes were normal
    NEG_FINDINGS

.

    Plasma glucosylceramide normalized
    BIOCHEMICAL

 already after

    splenectomy
    MEDICATION

 and

    further decreased
    BIOCHEMICAL

 after

    marrow transplantation
    MEDICATION

.

    Glucosylceramide in the erythrocytes was normal
    NEG_FINDINGS

 around a year after

    transplantation
    MEDICATION

. The

    enlarged liver normalized in size
    SYMPTOMS

 by 2 years.

    Gaucher cells were still present in the bone marrow
    MICROSCOPIC

 1 year after

    transplantation
    MEDICATION

    but had completely disappeared
    MICROSCOPIC

 at 3 years. The patient has

    grown 29 cm
    SYMPTOMS

 during the 5 years that have passed after

    transplantation
    MEDICATION

 compared to 1 cm/year during 3 years before. The patient has a

    slight obstructive ventilatory impairment
    SYMPTOMS

, and

    chest deformities have appeared
    SYMPTOMS

.

    Wechsler intelligence scale performance has slowly decreased
    SYMPTOMS

 after

    transplantation
    MEDICATION

. This may be caused by

    continued neuronal storage of glucosylceramide
    MICROSCOPIC

. Otherwise, this patient is active and healthy 5 years after

    bone marrow transplantation
    MEDICATION

.

splenectomy
allogeneic bone marrow transplantation
transplantation
splenectomy
marrow transplantation
transplantation
transplantation
transplantation
transplantation
bone marrow transplantation

Plasma glucosylceramide normalized
further decreased


Nodular sclerosing Hodgkin's disease in association with Gaucher's disease.

Gaucher's disease has been described in association with a number of disorders of the lymphoreticular system. The patient described in this report developed Hodgkin's disease after treatment in childhood for Gaucher's disease. A possible pathogenetic link between the two disorders is discussed, together with the role of ferritinaemia.

    Gaucher's disease
    DIAGNOSIS

 has been described in association with a number of

    disorders of the lymphoreticular system
    DIAGNOSIS

. The patient described in this report developed

    Hodgkin's disease
    DIAGNOSIS

 after

    treatment in childhood
    MEDICATION

 for

    Gaucher's disease
    DIAGNOSIS

. A possible pathogenetic link between the two disorders is discussed, together with the role of

    ferritinaemia
    BIOCHEMICAL

.

Gaucher's disease
disorders of the lymphoreticular system
Hodgkin's disease
Gaucher's disease


Intrafamilial clinical variability of type 1 Gaucher disease in a French-Canadian family.

Glucocerebroside beta-glucosidase (glucocerebrosidase) activity was determined from peripheral blood lymphocytes and cultured skin fibroblasts of eight full sibs in a French-Canadian family at risk for Gaucher disease, an autosomal recessive sphingolipidosis resulting from deficient glucocerebrosidase activity. The diagnosis of type 1, non-neuronopathic Gaucher disease was made in all of the five affected sibs on the basis of deficient (7.5 to 15.5% of control mean) glucocerebrosidase activity and absence of neurological involvement. Normal levels of enzyme activity were found in two of the three asymptomatic sibs. The third asymptomatic sib had an intermediate level (about 50% of control mean) of fibroblast and lymphocyte glucocerebrosidase activity, indicating that he is a carrier. Considerable clinical heterogeneity was noted among the five affected sibs. One patient is mildly affected and so far has not developed any orthopaedic complications associated with Gaucher disease. His haematological complications were also reversed after splenectomy 24 years ago. In contrast to this mild presentation, the patient's splenectomised sister has been very anaemic and thrombocytopenic. There have been severe orthopaedic complications associated with Gaucher disease, including vertebral compression, avascular necrosis, and pathological fracture of the long bones. The clinical picture of the other three affected sibs appeared to vary between the two extremes. Although the asymptomatic parents of the patients died many years ago, their heterozygous status with respect to Gaucher disease can be deduced by the presence of Gaucher homozygotes, normal homozygotes, and one heterozygote among their eight offspring. Present findings suggest that the clinical variability of type 1 Gaucher disease may be attributed to variable expressions of the same Gaucher mutant alleles, in addition to the presence of multiple mutant alleles that are widely disseminated in the population.

    Glucocerebroside beta-glucosidase (glucocerebrosidase) activity was determined from peripheral blood lymphocytes and cultured skin fibroblasts
    BIOCHEMICAL

 of eight

    full sibs
    FAMILY

 in a

    French-Canadian
    ETHNICITY

    family at risk for Gaucher disease
    FAMILY

, an

    autosomal recessive
    GENETICS

    sphingolipidosis
    DIAGNOSIS

 resulting from

    deficient glucocerebrosidase activity
    BIOCHEMICAL

. The diagnosis of

    type 1, non-neuronopathic Gaucher disease
    DIAGNOSIS

 was made in all of the five affected sibs on the basis of

    deficient (7.5 to 15.5% of control mean) glucocerebrosidase activity
    BIOCHEMICAL

 and

    absence of neurological involvement
    NEG_FINDINGS

.

    Normal levels of enzyme activity
    NEG_FINDINGS

 were found in two of the three

    asymptomatic sibs
    NEG_FINDINGS

. The third asymptomatic sib had an

    intermediate level (about 50% of control mean) of fibroblast and lymphocyte glucocerebrosidase activity
    BIOCHEMICAL

, indicating that

    he
    GENDER

 is a carrier. Considerable clinical heterogeneity was noted among the

    five affected sibs
    FAMILY

. One patient is

    mildly affected
    SYMPTOMS

 and so far has

    not developed any orthopaedic complications associated with Gaucher disease
    NEG_FINDINGS

.

    His
    GENDER

    haematological complications
    SYMPTOMS

 were also reversed after

    splenectomy 24 years ago
    MEDICATION

. In contrast to this mild presentation,

    the patient's splenectomised sister has been very anaemic and thrombocytopenic
    FAMILY

. There have been

    severe orthopaedic complications associated with Gaucher disease
    SYMPTOMS

, including

    vertebral compression
    SYMPTOMS

,

    avascular necrosis
    SYMPTOMS

, and

    pathological fracture of the long bones
    SYMPTOMS

. The clinical picture of the other three

    affected sibs
    FAMILY

 appeared to vary between the two extremes.

    Although the asymptomatic parents of the patients died many years ago
    FAMILY

, their

    heterozygous status with respect to Gaucher disease
    FAMILY

 can be deduced by the

    presence of Gaucher homozygotes, normal homozygotes, and one heterozygote among their eight offspring
    FAMILY

. Present findings suggest that the clinical variability of

    type 1 Gaucher disease
    DIAGNOSIS

 may be attributed to

    variable expressions of the same Gaucher mutant alleles
    GENETICS

, in addition to the presence of

    multiple mutant alleles
    GENETICS

 that are widely disseminated in the population.


Infantile Gaucher's disease: a case with neuronal storage.

The brain of a 17-month-old boy with infantile Gaucher's disease and oculomotor apraxia was studied by light and electron microscopy. Light microscopic examination showed large perivascular accumulations of Gaucher's cells in frontal lobe white matter, severe neuronal loss in the calcarine cortex and dentate nucleus of the cerebellum, and neuronophagia and microglial nodules in the brainstem. Electron microscopy demonstrated intraneuronal cytoplasmic inclusions containing twisted tubules characteristic of Gaucher's disease in both the oculomotor nucleus and a random sample of cortex.

The brain of a

    17-month-old
    AGE

    boy
    GENDER

 with

    infantile Gaucher's disease
    DIAGNOSIS

 and

    oculomotor apraxia
    SYMPTOMS

 was studied by

    light and electron microscopy
    PARACLINICAL

.

    Light microscopic examination
    PARACLINICAL

 showed

    large perivascular accumulations of Gaucher's cells in frontal lobe white matter
    MICROSCOPIC

,

    severe neuronal loss in the calcarine cortex and dentate nucleus of the cerebellum
    SYMPTOMS

, and

    neuronophagia and microglial nodules in the brainstem
    MICROSCOPIC

.

    Electron microscopy
    PARACLINICAL

 demonstrated

    intraneuronal cytoplasmic inclusions containing twisted tubules characteristic of Gaucher's disease in both the oculomotor nucleus and a random sample of cortex
    MICROSCOPIC

.


[Gaucher's disease of the 3d type (juvenile form)].

A case of Gaucher's disease, juvenile type is presented. Disease manifested with signs of hepatosplenomegaly, and thrombocytopenia. The typical Gaucher's cells were found in bone marrow aspiration. Acid phosphatase levels were 1.74 U. Bessey-Lowry/ml, 80.45% corresponding to the non-prostatic fraction. The enzymatic activity of glucosyl ceramide-beta-glucosidase was determined in a fibroblast culture, being its value of 0.42 mU/mg of protein (control: 3.2 mU/mg of protein). We comment on the existing relationship between the clinical types, as well as the therapeutic possibilities.

A case of

    Gaucher's disease, juvenile type
    DIAGNOSIS

 is presented. Disease manifested with signs of

    hepatosplenomegaly
    SYMPTOMS

, and

    thrombocytopenia
    BIOCHEMICAL

.

    The typical Gaucher's cells were found in bone marrow aspiration
    MICROSCOPIC

.

    Acid phosphatase levels were 1.74 U. Bessey-Lowry/ml, 80.45% corresponding to the non-prostatic fraction
    BIOCHEMICAL

. The

    enzymatic activity of glucosyl ceramide-beta-glucosidase
    BIOCHEMICAL

 was determined in a

    fibroblast culture
    MICROSCOPIC

, being its

    value of 0.42 mU/mg of protein (control: 3.2 mU/mg of protein)
    BIOCHEMICAL

. We comment on the existing relationship between the clinical types, as well as the therapeutic possibilities.


Gaucher's disease involving the maxillary sinuses.

A 46-year-old man with a long history of Gaucher's disease involving the spleen, bone marrow, and multiple bones presented with apparent sinusitis. He had radiologic opacification and histologically documented involvement by Gaucher's disease of the maxillary antra. Bony involvement of the mandible and maxilla has rarely been reported. To the best of our knowledge, this represents the first reported case of paranasal sinus involvement by Gaucher's disease.

A

    46-year-old
    AGE

    man
    GENDER

 with a

    long history of Gaucher's disease involving the spleen, bone marrow, and multiple bones
    MEDICATION

 presented with

    apparent sinusitis
    SYMPTOMS

.

    He
    GENDER

 had

    radiologic opacification
    SYMPTOMS

 and histologically documented

    involvement by Gaucher's disease of the maxillary antra
    MICROSCOPIC

.

    Bony involvement of the mandible and maxilla
    SYMPTOMS

 has rarely been reported. To the best of our knowledge, this represents the first reported case of

    paranasal sinus involvement
    SYMPTOMS

 by

    Gaucher's disease
    DIAGNOSIS

.


[Infantile type of Niemann-Pick disease with developmental defects of the central nervous system].

Clinical and morphologic manifestations of a rare disease developing, as a rule, in early life--an infantile variant of Niemann-Pick disease--are illustrated with a fatal case of a 6.5-month-old child. The diagnosis was established histochemically using, in particular, Smith-Dietrich method which provided differential diagnosis with cerebroside lipidosis (Gaucher's disease). In addition to typical enlargement of the liver, spleen and lymph nodes, cerebral and adrenal affection there appeared true porencephalia.

Clinical and morphologic manifestations of a rare disease developing, as a rule, in

    early life
    AGE

--an

    infantile variant of Niemann-Pick disease
    DIAGNOSIS

--are illustrated with a fatal case of a

    6.5-month-old
    AGE

    child
    AGE

. The diagnosis was established

    histochemically
    PARACLINICAL

 using, in particular,

    Smith-Dietrich method
    PARACLINICAL

 which provided differential diagnosis with

    cerebroside lipidosis (Gaucher's disease)
    DIAGNOSIS

. In addition to typical

    enlargement of the liver, spleen and lymph nodes
    SYMPTOMS

,

    cerebral and adrenal affection
    SYMPTOMS

 there appeared

    true porencephalia
    SYMPTOMS

.


Nephrotic syndrome and renal failure associated with a novel glycolipid storage disorder.

A 57-year-old Caucasian male presented with severe nephrotic syndrome and diffuse organomegaly; he subsequently developed renal failure and died. Intracellular, crystalloid material was identified by light and electron microscopy in bone marrow, liver, spleen, mesenteric lymph nodes, and kidneys. Tissue extraction analysis identified the material as glucocerebroside and its immediate precursor, ceramide lactoside. Although Gaucher's disease cannot be completely excluded, glycolipid profiles do not conform to those of known storage disorders. Additionally, electron-microscopic studies indicate that the structural features of the glycolipid deposits are different from those of previously described storage diseases. These findings suggest a unique crystalloid deposition as the probable cause of a multisystem process, which was associated with renal insufficiency and death.

A

    57-year-old
    AGE

    Caucasian
    ETHNICITY

    male
    GENDER

 presented with

    severe nephrotic syndrome
    SYMPTOMS

 and

    diffuse organomegaly
    SYMPTOMS

;

    he
    GENDER

 subsequently developed

    renal failure
    SYMPTOMS

 and

    died
    SYMPTOMS

.

    Intracellular, crystalloid material was identified
    MICROSCOPIC

 by

    light and electron microscopy
    PARACLINICAL

    in bone marrow, liver, spleen, mesenteric lymph nodes, and kidneys
    MICROSCOPIC

.

    Tissue extraction analysis
    PARACLINICAL

 identified the

    material as glucocerebroside and its immediate precursor, ceramide lactoside
    MICROSCOPIC

. Although

    Gaucher's disease cannot be completely excluded
    DIAGNOSIS

,

    glycolipid profiles do not conform to those of known storage disorders
    NEG_FINDINGS

. Additionally,

    electron-microscopic studies
    PARACLINICAL

 indicate that the structural features

    of the glycolipid deposits
    MICROSCOPIC

 are different from those of previously described

    storage diseases
    MICROSCOPIC

. These findings suggest a

    unique crystalloid deposition
    MICROSCOPIC

 as the probable cause of a

    multisystem process
    DIAGNOSIS

, which was associated with

    renal insufficiency
    SYMPTOMS

 and

    death
    SYMPTOMS

.

severe nephrotic syndrome
diffuse organomegaly
renal failure
died
renal insufficiency
death


[Sternocostoclavicular hyperostosis. Nosological concepts].

The term sternocostoclavicular hyperostosis groups affections of different pathogenicity. These result from an ossifying enthesiopathy, either inflammatory, isolated to the thoracic wall anteriorly or combined with a spondylarthropathy, particularly ankylosing spondylitis, or degenerative, the anterior thoracic hyperostosis usually being part of an ensheathing vertebral hyperostosis. A differential diagnosis is anterior thoracic hyperostosis due to an inflammatory osteopathy occurring in young patients and often associated with other bone lesions of pelvis and spine or long bones.

The term

    sternocostoclavicular hyperostosis
    SYMPTOMS

 groups affections of different pathogenicity. These result from an

    ossifying enthesiopathy
    DIAGNOSIS

, either

    inflammatory, isolated to the thoracic wall anteriorly
    SYMPTOMS

 or combined with a

    spondylarthropathy
    DIAGNOSIS

, particularly

    ankylosing spondylitis
    DIAGNOSIS

, or

    degenerative
    DIAGNOSIS

, the

    anterior thoracic hyperostosis
    SYMPTOMS

 usually being part of an

    ensheathing vertebral hyperostosis
    SYMPTOMS

. A

    differential diagnosis
    PARACLINICAL

 is

    anterior thoracic hyperostosis
    SYMPTOMS

 due to an

    inflammatory osteopathy
    DIAGNOSIS

 occurring in

    young
    AGE

 patients and often associated with

    other bone lesions of pelvis and spine or long bones
    SYMPTOMS

.

ossifying enthesiopathy
spondylarthropathy
ankylosing spondylitis
degenerative
inflammatory osteopathy


Regression of the radiological changes of Gaucher's disease following bone marrow transplantation.

Seven children with Type I Gaucher's disease have been treated with bone marrow transplantation (BMT). One patient died from the complications of BMT. In five patients computed tomography (CT) of the femora showed initially high attenuation in the marrow, returning towards normal after successful BMT. One of these patients also showed clearing of pulmonary infiltrates following treatment. In the first patient in the series no pre-transplant CT measurements were carried out but plain radiographs have demonstrated a return to normal shape of her femora 21/2 years after BMT. It is hoped that CT of the marrow cavities may provide a simple, non-invasive method for monitoring progress following BMT.

Seven

    children
    AGE

 with

    Type I Gaucher's disease
    DIAGNOSIS

 have been treated with

    bone marrow transplantation (BMT)
    MEDICATION

. One patient

    died from the complications of BMT
    SYMPTOMS

. In five patients

    computed tomography (CT) of the femora
    PARACLINICAL

 showed

    initially high attenuation in the marrow, returning towards normal
    SYMPTOMS

 after successful

    BMT
    MEDICATION

. One of these patients also showed

    clearing of pulmonary infiltrates
    SYMPTOMS

 following treatment. In the first patient in the series

    no pre-transplant CT measurements were carried out
    NEG_FINDINGS

 but

    plain radiographs
    PARACLINICAL

 have demonstrated a

    return to normal shape of her femora 21/2 years after BMT
    SYMPTOMS

. It is hoped that

    CT of the marrow cavities
    PARACLINICAL

 may provide a simple, non-invasive method for monitoring progress following

    BMT
    MEDICATION

.

bone marrow transplantation (BMT)
BMT
BMT


Gaucher disease: treatment of hypersplenism with splenic embolization.

Hypersplenism is a frequent complication of Gaucher disease requiring splenectomy. A patient with Gaucher disease and severe hypersplenism was treated with partial splenic embolization to avoid the increased risk of serious infectious complications and deterioration of the disease associated with splenectomy. A first embolization (25% ablation) was performed at 4 years. Because of persisting abdominal discomfort, failure to thrive and signs of hypersplenism a second embolization (40-50% ablation) was performed 18 months later. Subsequently, the patient's health improved remarkably and 4 years later he achieved normal growth, maintains normal haematologic parameters, is free of symptoms and has no skeletal abnormalities. No serious infections have occurred. The size of the liver and the spleen has not changed appreciably. It appears that partial splenic embolization may be preferable to splenectomy in patients with Gaucher disease, especially in those of young age.

    Hypersplenism
    BIOCHEMICAL

 is a frequent complication of

    Gaucher disease
    DIAGNOSIS

 requiring

    splenectomy
    MEDICATION

. A patient with

    Gaucher disease
    DIAGNOSIS

 and

    severe hypersplenism
    BIOCHEMICAL

 was treated with

    partial splenic embolization
    MEDICATION

 to avoid the increased risk of

    serious infectious complications
    SYMPTOMS

 and

    deterioration of the disease
    SYMPTOMS

 associated with

    splenectomy
    MEDICATION

. A

    first embolization (25% ablation)
    MEDICATION

 was performed

    at 4 years
    AGE

. Because of

    persisting abdominal discomfort
    SYMPTOMS

,

    failure to thrive
    SYMPTOMS

 and

    signs of hypersplenism
    SYMPTOMS

 a

    second embolization (40-50% ablation)
    MEDICATION

 was performed 18 months later. Subsequently, the patient's health improved remarkably and 4 years later

    he
    GENDER

 achieved

    normal growth
    SYMPTOMS

,

    maintains normal haematologic parameters
    BIOCHEMICAL

, is

    free of symptoms
    NEG_FINDINGS

 and has

    no skeletal abnormalities
    NEG_FINDINGS

.

    No serious infections
    NEG_FINDINGS

 have occurred. The

    size of the liver and the spleen has not changed appreciably
    NEG_FINDINGS

. It appears that

    partial splenic embolization
    MEDICATION

 may be preferable to

    splenectomy
    MEDICATION

 in patients with

    Gaucher disease
    DIAGNOSIS

, especially in those of

    young age
    AGE

.

Gaucher disease
Gaucher disease
Gaucher disease

splenectomy
partial splenic embolization
splenectomy
first embolization (25% ablation)
second embolization (40-50% ablation)
partial splenic embolization
splenectomy

serious infectious complications
deterioration of the disease
persisting abdominal discomfort
failure to thrive
signs of hypersplenism
normal growth


Adult Gaucher disease in association with acute leukaemia.

A non-Jewish patient diagnosed as having Gaucher disease at the age of 67 is described. Fourteen months after presentation he was diagnosed as having acute myeloid leukaemia. A possible association between Gaucher disease and acute myeloid leukaemia is suggested.

A

    non-Jewish
    ETHNICITY

 patient diagnosed as having

    Gaucher disease
    DIAGNOSIS

 at the

    age of 67
    AGE

 is described. Fourteen months after presentation

    he
    GENDER

 was diagnosed as having

    acute myeloid leukaemia
    DIAGNOSIS

. A possible association between

    Gaucher disease
    DIAGNOSIS

 and

    acute myeloid leukaemia
    DIAGNOSIS

 is suggested.

Gaucher disease
acute myeloid leukaemia
Gaucher disease
acute myeloid leukaemia


Spinal cord decompression for Gaucher's disease.

We report an individual with Type I nonneuronopathic Gaucher's disease who experienced the rare complication of spinal cord compression secondary to a sclerotic vertebral fracture. He successfully underwent anterolateral spinal cord decompression and spinal fusion despite the severity of his generalized skeletal disease.

We report an individual with

    Type I nonneuronopathic Gaucher's disease
    DIAGNOSIS

 who experienced the rare complication of

    spinal cord compression secondary to a sclerotic vertebral fracture
    SYMPTOMS

.

    He
    GENDER

 successfully underwent

    anterolateral spinal cord decompression and spinal fusion
    MEDICATION

 despite the severity of his

    generalized skeletal disease
    SYMPTOMS

.


Partial splenectomy for Gaucher's disease.

Gaucher's disease is an autosomal recessive disorder caused by deficiency of beta glucocerebrosidase, resulting in an accumulation of glucocerebroside in the reticuloendothelial system. These patients have massive splenomegaly and bone pain, but may have normal life expectancy. Traditionally, splenectomy has been used to treat hypersplenism, but may be associated with a high incidence of postsplenectomy sepsis and accelerated hepatic and bone lipid deposition. Two children are reported who had partial splenectomy for symptoms of Gaucher's disease. Both patients had laboratory evidence of hypersplenism. A 90% splenectomy was performed, and the residual splenic fragment was wrapped in Vicryl mesh. Both patients are currently asymptomatic with normal hematologic parameters. Postoperative radionuclide scans demonstrate increase in the size of the residual splenic fragment. Partial splenectomy may benefit patients with Gaucher's disease, but long-term follow-up care is necessary.

    Gaucher's disease
    DIAGNOSIS

 is an

    autosomal recessive disorder
    GENETICS

 caused by

    deficiency of beta glucocerebrosidase
    BIOCHEMICAL

, resulting in an

    accumulation of glucocerebroside in the reticuloendothelial system
    MICROSCOPIC

. These patients have

    massive splenomegaly
    SYMPTOMS

 and

    bone pain
    SYMPTOMS

, but may have

    normal life expectancy
    NEG_FINDINGS

. Traditionally,

    splenectomy
    MEDICATION

 has been used to treat

    hypersplenism
    BIOCHEMICAL

, but may be associated with a high incidence of

    postsplenectomy sepsis
    SYMPTOMS

 and

    accelerated hepatic and bone lipid deposition
    MICROSCOPIC

. Two

    children
    AGE

 are reported who had

    partial splenectomy
    MEDICATION

 for symptoms of

    Gaucher's disease
    DIAGNOSIS

. Both patients had

    laboratory evidence of hypersplenism
    BIOCHEMICAL

. A

    90% splenectomy
    MEDICATION

 was performed, and

    the residual splenic fragment was wrapped in Vicryl mesh
    MEDICATION

. Both patients are currently

    asymptomatic
    NEG_FINDINGS

 with

    normal hematologic parameters
    NEG_FINDINGS

.

    Postoperative radionuclide scans
    PARACLINICAL

 demonstrate

    increase in the size of the residual splenic fragment
    MICROSCOPIC

.

    Partial splenectomy
    MEDICATION

 may benefit patients with

    Gaucher's disease
    DIAGNOSIS

, but long-term follow-up care is necessary.

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

deficiency of beta glucocerebrosidase
hypersplenism
laboratory evidence of hypersplenism

massive splenomegaly
bone pain
postsplenectomy sepsis

normal life expectancy
asymptomatic
normal hematologic parameters


Beneficial effect of pre-transplant splenectomy on displacement bone marrow transplantation for Gaucher's syndrome.

2 patients with fast and 4 with medium varieties of Gaucher's syndrome were treated by displacement bone marrow transplantation to install a donor enzyme factory for life. Immunoprophylaxis was given to prevent host impairment of normal enzymes. 5 patients showed rapid and remarkable improvement and were leading fully active lives at 310-1207 days postgraft. Hypersplenism caused the death of 1 patient and a stormy time for another. Pre-transplant elective splenectomy hastened recovery.

2 patients with fast and 4 with

    medium varieties
    DIAGNOSIS

 of

    Gaucher's syndrome
    DIAGNOSIS

 were treated by

    displacement bone marrow transplantation
    MEDICATION

 to

    install a donor enzyme factory for life
    MEDICATION

.

    Immunoprophylaxis
    MEDICATION

 was given to prevent

    host impairment of normal enzymes
    BIOCHEMICAL

. 5 patients showed

    rapid and remarkable improvement
    SYMPTOMS

 and were

    leading fully active lives
    SYMPTOMS

 at 310-1207 days

    postgraft
    MEDICATION

.

    Hypersplenism
    BIOCHEMICAL

 caused the

    death
    SYMPTOMS

 of 1 patient and a

    stormy time
    SYMPTOMS

 for another.

    Pre-transplant elective splenectomy
    MEDICATION

 hastened recovery.

host impairment of normal enzymes
Hypersplenism

rapid and remarkable improvement
leading fully active lives
death
stormy time


Pseudo-Gaucher cells in the bone marrow of a patient with Hodgkin's disease.

The authors studied an 18-year-old woman with stage IIIB nodular sclerosis Hodgkin's disease whose bone marrow contained abnormal storage cells that resembled Gaucher cells by light microscopic examination ("pseudo-Gaucher" cells). Electron microscopic examination revealed that these cells differed from true Gaucher cells and resembled storage cells previously described in chronic myelogenous leukemia. The patient's peripheral blood leukocyte beta-glucosidase and serum acid phosphatase levels were elevated, ruling out the diagnosis of inherited Gaucher's disease. After treatment with six monthly cycles of systemic chemotherapy (nitrogen mustard, vincristine, procarbazine, bleomycin, doxorubicin, and prednisone), all signs of Hodgkin's disease and pseudo-Gaucher cells disappeared. Repeat leukocyte beta-glucosidase and serum acid phosphatase levels were unchanged. The present case is unique with its documentation of classical enzyme patterns for beta-glucosidase and acid phosphatase and electron microscopic features. The authors postulate that pseudo-Gaucher cells result from excessive cell breakdown with an overload of available beta-glucosidase.

The authors studied an

    18-year-old
    AGE

    woman
    GENDER

 with

    stage IIIB nodular sclerosis Hodgkin's disease
    DIAGNOSIS

 whose

    bone marrow contained abnormal storage cells that resembled Gaucher cells
    MICROSCOPIC

 by

    light microscopic examination
    PARACLINICAL

    ("pseudo-Gaucher" cells)
    MICROSCOPIC

.

    Electron microscopic examination
    PARACLINICAL

 revealed that these

    cells differed from true Gaucher cells and resembled storage cells previously described in chronic myelogenous leukemia
    MICROSCOPIC

. The patient's

    peripheral blood leukocyte beta-glucosidase and serum acid phosphatase levels were elevated
    BIOCHEMICAL

,

    ruling out the diagnosis of inherited Gaucher's disease
    NEG_FINDINGS

. After

    treatment with six monthly cycles of systemic chemotherapy (nitrogen mustard, vincristine, procarbazine, bleomycin, doxorubicin, and prednisone)
    MEDICATION

,

    all signs of Hodgkin's disease
    SYMPTOMS

 and

    pseudo-Gaucher cells disappeared
    MICROSCOPIC

.

    Repeat leukocyte beta-glucosidase and serum acid phosphatase levels were unchanged
    NEG_FINDINGS

. The present case is unique with its documentation of

    classical enzyme patterns for beta-glucosidase and acid phosphatase
    BIOCHEMICAL

 and

    electron microscopic features
    PARACLINICAL

. The authors postulate that

    pseudo-Gaucher cells
    MICROSCOPIC

 result from

    excessive cell breakdown
    MICROSCOPIC

 with an

    overload of available beta-glucosidase
    BIOCHEMICAL

.


The varied clinical and laboratory manifestations of type II Gaucher's disease.

An infant of Arab extraction with the Type II form of Gaucher's disease is described. His clinical presentation was unusual because in addition to the extensive neurological involvement and marked hepatosplenomegaly a severe congestive cardiomyopathy and renal tubular dysfunction were present. In addition, marked hypergammaglobulinemia and raised serum angiotensin converting enzyme levels were found. It is suggested that these varied manifestations may be ascribed to the consequences of glucocerebroside deposition within the macrophages of the reticuloendothelial system.

An

    infant
    AGE

 of

    Arab extraction
    ETHNICITY

 with the

    Type II form of Gaucher's disease
    DIAGNOSIS

 is described.

    His
    GENDER

 clinical presentation was unusual because in addition to the

    extensive neurological involvement
    SYMPTOMS

 and

    marked hepatosplenomegaly
    SYMPTOMS

 a

    severe congestive cardiomyopathy
    SYMPTOMS

 and

    renal tubular dysfunction
    SYMPTOMS

 were present. In addition,

    marked hypergammaglobulinemia
    BIOCHEMICAL

 and

    raised serum angiotensin converting enzyme levels
    BIOCHEMICAL

 were found. It is suggested that these varied manifestations may be ascribed to the consequences of

    glucocerebroside deposition within the macrophages of the reticuloendothelial system
    MICROSCOPIC

.

extensive neurological involvement
marked hepatosplenomegaly
severe congestive cardiomyopathy
renal tubular dysfunction


[Case report of Gaucher's disease].

The case of a 42 years old man suffering from Gaucher's disease is reported. The primary diagnosis was liver cirrhosis based on echographic and scintigraphic examinations. The following signs were found: thrombocytopenia, slight hemolysis, shortened life of the erythrocytes with considerable sequestration in the spleen, abnormal flocculation tests, increased acid phosphatase. The X-ray examination revealed irregularly oval light spots with different size and form and well cut outlines in the skull and a zone of bone resorption in the right shoulder joint. The liver needle biopsy showed parenchymal infiltration with Gaucher's cells. The above mentioned deviations and the family heredity of the patients suggested the diagnosis of an adult form of Gaucher's disease. The fibroplastic changes in the liver including formation of septa led to the suggestion of a link between Gaucher's disease and liver cirrhosis.

The case of a

    42 years old
    AGE

    man
    GENDER

 suffering from

    Gaucher's disease
    DIAGNOSIS

 is reported. The primary diagnosis was

    liver cirrhosis
    DIAGNOSIS

 based on

    echographic and scintigraphic examinations
    PARACLINICAL

. The following signs were found:

    thrombocytopenia
    BIOCHEMICAL

,

    slight hemolysis
    BIOCHEMICAL

,

    shortened life of the erythrocytes with considerable sequestration in the spleen
    MICROSCOPIC

,

    abnormal flocculation tests
    BIOCHEMICAL

,

    increased acid phosphatase
    BIOCHEMICAL

. The

    X-ray examination
    PARACLINICAL

 revealed

    irregularly oval light spots with different size and form and well cut outlines in the skull
    SYMPTOMS

 and a

    zone of bone resorption in the right shoulder joint
    SYMPTOMS

. The

    liver needle biopsy
    PARACLINICAL

 showed

    parenchymal infiltration with Gaucher's cells
    MICROSCOPIC

. The above mentioned deviations and the

    family heredity of the patients
    FAMILY

 suggested the diagnosis of an

    adult form of Gaucher's disease
    DIAGNOSIS

. The

    fibroplastic changes in the liver
    MICROSCOPIC

 including

    formation of septa
    SYMPTOMS

 led to the suggestion of a link between

    Gaucher's disease
    DIAGNOSIS

 and

    liver cirrhosis
    DIAGNOSIS

.

Gaucher's disease
liver cirrhosis
adult form of Gaucher's disease
Gaucher's disease
liver cirrhosis

thrombocytopenia
slight hemolysis
abnormal flocculation tests
increased acid phosphatase


[Gaucher disease and pregnancy--a case report].

Reporting an own case the authors describe the unusual combination of Gaucher's Disease and pregnancy. They suggest with regard to the possibility of hepatic and/or lienal rupture in cases with extended hepatosplenomegaly the primary caesarean section.

Reporting an own case the authors describe the

    unusual combination of Gaucher's Disease and pregnancy
    DIAGNOSIS

. They suggest with regard to the possibility of

    hepatic and/or lienal rupture
    SYMPTOMS

 in cases with

    extended hepatosplenomegaly
    SYMPTOMS

 the

    primary caesarean section
    MEDICATION

.

hepatic and/or lienal rupture
extended hepatosplenomegaly


Gaucher disease of the liver: CT appearance.

We present a child with Gaucher disease with hepatic involvement that caused portal hypertension. Computerized tomography (CT) showed distortion of liver parenchyma and central necrosis of the liver.

We present a

    child
    AGE

 with

    Gaucher disease
    DIAGNOSIS

 with

    hepatic involvement
    SYMPTOMS

 that caused

    portal hypertension
    SYMPTOMS

.

    Computerized tomography (CT)
    PARACLINICAL

 showed

    distortion of liver parenchyma
    SYMPTOMS

 and

    central necrosis of the liver
    MICROSCOPIC

.

hepatic involvement
portal hypertension
distortion of liver parenchyma


Elevation of serum beta-hexosaminidase and alpha-D-mannosidase in type 2 Gaucher disease: a clinical and biochemical study.

We report a case of a black infant who died at 9 months of age with clinical and pathological findings consistent with the acute neuronopathic form of Gaucher disease (Type 2). Analysis of peripheral blood platelets obtained from this child demonstrated very low levels of beta-glucosidase activity. beta-hexosaminidase (HEX) activity in the serum, however, was 30 times greater than the level in control sera and 15 times greater than the level observed in individuals affected with the chronic form of Gaucher disease (Type 1). Similarly, alpha-D-mannosidase (MANN) activity in the proband's serum was significantly elevated when compared with controls, and chronic Gaucher disease patients. We postulate that the cause of the elevation of these lysosomal enzymes is similar to the cause of elevation in Type 1 individuals but that patients with Type 2 Gaucher disease have a more serious cellular defect.

We report a case of a

    black
    AGE

    infant
    AGE

 who

    died
    SYMPTOMS

    at 9 months of age
    AGE

 with clinical and pathological findings consistent with the

    acute neuronopathic form of Gaucher disease (Type 2)
    DIAGNOSIS

.

    Analysis of peripheral blood platelets obtained
    PARACLINICAL

 from this

    child
    AGE

 demonstrated

    very low levels of beta-glucosidase activity
    BIOCHEMICAL

.

    beta-hexosaminidase (HEX) activity in the serum, however, was 30 times greater than the level in control sera and 15 times greater than the level observed
    BIOCHEMICAL

 in individuals affected with the

    chronic form of Gaucher disease (Type 1)
    DIAGNOSIS

. Similarly,

    alpha-D-mannosidase (MANN) activity in the proband's serum was significantly elevated
    BIOCHEMICAL

 when compared with controls, and

    chronic Gaucher disease patients
    DIAGNOSIS

. We postulate that the cause of the

    elevation of these lysosomal enzymes
    BIOCHEMICAL

 is similar to the cause of

    elevation
    BIOCHEMICAL

 in

    Type 1 individuals
    DIAGNOSIS

 but that patients with

    Type 2 Gaucher disease
    DIAGNOSIS

 have a more serious cellular defect.


Osteomyelitis in Gaucher disease.

A relatively common complication of Gaucher disease, the so-called crisis, frequently is difficult to differentiate from acute osteomyelitis. We reviewed the cases of forty-nine patients with Gaucher disease who were treated at the Massachusetts General Hospital and found that eleven patients had required admission to the hospital for an acute symptom complex that represented either a crisis or an infection. Five of the patients proved to have acute hematogenous osteomyelitis. The delayed diagnosis of the infection in three of the patients with osteomyelitis led to an unsatisfactory outcome.

A relatively common complication of

    Gaucher disease
    DIAGNOSIS

, the so-called

    crisis
    DIAGNOSIS

, frequently is difficult to differentiate from

    acute osteomyelitis
    DIAGNOSIS

. We reviewed the cases of forty-nine patients with

    Gaucher disease
    DIAGNOSIS

 who were treated at the Massachusetts General Hospital and found that eleven patients had required

    admission to the hospital
    MEDICATION

 for an

    acute symptom complex
    SYMPTOMS

 that represented either a crisis or an

    infection
    SYMPTOMS

. Five of the patients proved to have

    acute hematogenous osteomyelitis
    DIAGNOSIS

. The delayed diagnosis of the

    infection
    SYMPTOMS

 in three of the patients with

    osteomyelitis
    DIAGNOSIS

 led to an unsatisfactory outcome.

Gaucher disease
crisis
acute osteomyelitis
Gaucher disease
acute hematogenous osteomyelitis
osteomyelitis

acute symptom complex
infection
infection


A case is reported of Gaucher's disease in pregnancy associated with portal hypertension. Despite this rare and hazardous complication, the pregnancy, labor, and puerperium were uneventful.

A case is reported of

    Gaucher's disease
    DIAGNOSIS

 in

    pregnancy
    DIAGNOSIS

 associated with

    portal hypertension
    SYMPTOMS

. Despite this rare and hazardous complication, the

    pregnancy
    SYMPTOMS

, labor, and

    puerperium were uneventful
    NEG_FINDINGS

.


Gaucher's disease in a patient with chronic active hepatitis.

Gaucher's disease, an inherited metabolic disorder, may cause hepatic fibrosis, but hepatic inflammation does not occur as part of the disorder. The case of an 18-year-old girl of Ashkenazic Jewish ancestry with chronic active hepatitis and coexistent Gaucher's disease is presented. The clinical course of remissions and exacerbations of the disease activity was typical of "autoimmune" chronic active hepatitis and seemed unaffected by the coexistence of Gaucher's disease. Steroid and immunosuppressive treatment resulted in prompt resolution of the chronic hepatitis. Gaucher's disease results in B cell stimulation and polyclonal gammopathy, which may have contributed to the hypergammaglobulinemia associated with idiopathic ("autoimmune") chronic hepatitis in this case.

    Gaucher's disease
    DIAGNOSIS

, an

    inherited metabolic disorder
    GENETICS

, may cause

    hepatic fibrosis
    SYMPTOMS

, but

    hepatic inflammation
    SYMPTOMS

 does not occur as part of the disorder. The case of an

    18-year-old
    AGE

    girl
    GENDER

 of

    Ashkenazic Jewish ancestry
    ETHNICITY

 with

    chronic active hepatitis
    DIAGNOSIS

 and

    coexistent Gaucher's disease
    DIAGNOSIS

 is presented. The clinical course of

    remissions and exacerbations of the disease activity
    SYMPTOMS

 was typical of

    "autoimmune" chronic active hepatitis
    DIAGNOSIS

 and seemed unaffected by the

    coexistence of Gaucher's disease
    NEG_FINDINGS

.

    Steroid and immunosuppressive treatment
    MEDICATION

 resulted in

    prompt resolution of the chronic hepatitis
    SYMPTOMS

.

    Gaucher's disease
    DIAGNOSIS

 results in

    B cell stimulation
    MICROSCOPIC

 and

    polyclonal gammopathy
    BIOCHEMICAL

, which may have contributed to the

    hypergammaglobulinemia
    BIOCHEMICAL

 associated with

    idiopathic ("autoimmune") chronic hepatitis
    DIAGNOSIS

 in this case.


Pseudogaucher cells in Mycobacterium avium intracellulare infections in acquired immune deficiency syndrome (AIDS).

This report describes a 28-year-old woman with the acquired immune deficiency syndrome (AIDS) with culture-proven disseminated Mycobacterium avium intracellulare infection. The histopathologic and cytologic features in this case were unique in that these organisms that stained positively with the Ziehl-Neelsen and periodic acid-Schiff (PAS) stains were numerous, present intracellularly within histiocytes, transforming them into pseudogaucher cells. Differential diagnostic criteria for pseudogaucher cells and abnormal macrophage handling of the intracellular organisms in AIDS are discussed.

This report describes a

    28-year-old
    AGE

    woman
    GENDER

 with the

    acquired immune deficiency syndrome (AIDS)
    DIAGNOSIS

 with

    culture-
    DIAGNOSIS

proven

    disseminated Mycobacterium avium intracellulare infection
    DIAGNOSIS

. The

    histopathologic and cytologic
    PARACLINICAL

 features in this case were unique in that

    these organisms that stained positively with the Ziehl-Neelsen and periodic acid-Schiff (PAS) stains
    MICROSCOPIC

    were numerous, present intracellularly within histiocytes, transforming them into pseudogaucher cells
    MICROSCOPIC

. Differential diagnostic criteria for

    pseudogaucher cells
    MICROSCOPIC

 and

    abnormal macrophage handling of the intracellular organisms
    MICROSCOPIC

 in

    AIDS
    DIAGNOSIS

 are discussed.


Gaucher's disease associated with chronic lymphocytic leukaemia.

The association of Gaucher's disease with chronic lymphocytic leukaemia (CLL) is very rare. To our knowledge only five cases have been reported (Chang-Lo, Yam & Rubenstone 1967; Chang-Lo et al. 1975; Fox et al. 1984; Lee 1982; Mark, Dominguez & Rywlin 1982). We report a patient with this association, the CLL had been diagnosed 12 years after the demonstration of Gaucher's disease.

The

    association of Gaucher's disease with chronic lymphocytic leukaemia (CLL)
    DIAGNOSIS

 is very rare. To our knowledge only five cases have been reported (Chang-Lo, Yam & Rubenstone 1967; Chang-Lo et al. 1975; Fox et al. 1984; Lee 1982; Mark, Dominguez & Rywlin 1982). We report a patient with this association, the

    CLL
    DIAGNOSIS

 had been diagnosed 12 years after the demonstration of

    Gaucher's disease
    DIAGNOSIS

.


Enzyme activities and phospholipid storage patterns in brain and spleen samples from Niemann-Pick disease variants: a comparison of neuropathic and non-neuropathic forms.

Phospholipid levels and enzyme activities were measured in brain and spleen samples from patients with the three major variants of Niemann-Pick disease. Accumulations of sphingomyelin and bis(monoacylglycero)phosphate were demonstrated in spleen from types A and B and group C Niemann-Pick disease, whereas only in type A Niemann-Pick brain was the sphingomyelin concentration increased. Sphingomyelinase activity was markedly deficient in type A Niemann-Pick brain and spleen but residual activity of approximately 12% of control was measured in type B Niemann-Pick brain. Normal or raised sphingomyelinase and beta-glucosidase activities were measured in group C Niemann-Pick brain and spleen. Significant (17% of control) residual beta-glucosidase activity was also measured in non-neuropathic Gaucher brain. Normal levels of neutral sphingomyelinase activity were measured in brain samples from the three variants of Niemann-Pick disease. Acid sphingomyelinase activity in group C Niemann-Pick brain appeared normal with respect to enzyme extraction, pH optimum (pH 5.0) and apparent Km (approximately 0.4 mmol/L). Isoelectric focusing of brain sphingomyelinase revealed a degree of heterogeneity with activity peaks between pI 4.5 and 6.5. No defect was observed in group C Niemann-Pick brain and, although attenuated, all peaks were present in type B Niemann-Pick brain.

    Phospholipid levels and enzyme activities
    BIOCHEMICAL

 were

    measured in brain and spleen samples
    PARACLINICAL

 from patients with the three major variants of

    Niemann-Pick disease
    DIAGNOSIS

.

    Accumulations of sphingomyelin and bis(monoacylglycero)phosphate were demonstrated in spleen
    MICROSCOPIC

 from

    types A and B and group C Niemann-Pick disease
    DIAGNOSIS

, whereas only in

    type A Niemann-Pick brain
    DIAGNOSIS

 was

    the sphingomyelin concentration increased
    MICROSCOPIC

.

    Sphingomyelinase activity was markedly deficient
    BIOCHEMICAL

 in

    type A Niemann-Pick brain and spleen
    MICROSCOPIC

 but

    residual activity of approximately 12% of control
    BIOCHEMICAL

 was measured in

    type B Niemann-Pick brain
    MICROSCOPIC

.

    Normal or raised sphingomyelinase and beta-glucosidase activities
    NEG_FINDINGS

 were measured in

    group C Niemann-Pick brain and spleen
    DIAGNOSIS

.

    Significant (17% of control) residual beta-glucosidase activity was also measured
    BIOCHEMICAL

 in

    non-neuropathic Gaucher brain
    MICROSCOPIC

.

    Normal levels of neutral sphingomyelinase activity were measured in brain samples
    NEG_FINDINGS

 from the three variants of

    Niemann-Pick disease
    DIAGNOSIS

.

    Acid sphingomyelinase activity in group C Niemann-Pick brain appeared normal
    NEG_FINDINGS

 with respect to enzyme extraction, pH optimum (pH 5.0) and

    apparent Km (approximately 0.4 mmol/L)
    BIOCHEMICAL

.

    Isoelectric focusing of brain sphingomyelinase
    PARACLINICAL

 revealed a degree of heterogeneity with

    activity peaks between pI 4.5 and 6.5
    BIOCHEMICAL

.

    No defect
    NEG_FINDINGS

 was observed in

    group C Niemann-Pick brain
    DIAGNOSIS

 and, although attenuated, all peaks were present in

    type B Niemann-Pick brain
    DIAGNOSIS

.


Multiple plasmocytomas of the liver and the spleen.

Imaging in a patient with multiple myeloma and Gaucher's disease showed space-occupying lesions in the liver and spleen. These were found to be plasmocytomas on histologic examination.

    Imaging
    PARACLINICAL

 in a patient with

    multiple myeloma
    DIAGNOSIS

 and

    Gaucher's disease
    DIAGNOSIS

 showed

    space-occupying lesions in the liver and spleen
    SYMPTOMS

. These were found to be

    plasmocytomas
    MICROSCOPIC

 on

    histologic examination
    PARACLINICAL

.


Chemical shift imaging of bone marrow: preliminary experience.

A phase-contrast method of chemical shift imaging was used to evaluate bone marrow in normal volunteers and in patients with metabolic, inflammatory, traumatic, and neoplastic disorders. Five normal volunteers were examined in order to obtain preliminary data on normal patterns of signal intensity in hematopoietic and fatty marrow using both conventional magnetic resonance imaging and proton chemical shift imaging. Normally, hematopoietic marrow yields low signal intensity on phase-contrast images; pathologic conditions affecting hematopoietic marrow typically result in increased signal intensity due to either accumulated lipid or water. Because of its high fat content, yellow marrow normally yields high signal intensity on phase-contrast images, whereas abnormal conditions usually result in decreased phase-contrast signal intensity due to increased tissue water. Proton chemical shift imaging is likely to be a valuable supplement to standard magnetic resonance imaging techniques in the study of bone marrow in vivo.

A

    phase-contrast method of chemical shift imaging
    PARACLINICAL

 was used to

    evaluate bone marrow
    PARACLINICAL

 in normal volunteers and in patients with

    metabolic
    DIAGNOSIS

, inflammatory,

    traumatic
    SYMPTOMS

, and

    neoplastic disorders
    DIAGNOSIS

. Five normal volunteers were examined in order to obtain preliminary data on normal patterns of signal intensity in

    hematopoietic and fatty marrow
    MICROSCOPIC

 using both

    conventional magnetic resonance imaging
    PARACLINICAL

 and

    proton chemical shift imaging
    PARACLINICAL

. Normally,

    hematopoietic marrow
    MICROSCOPIC

 yields

    low signal intensity on phase-contrast images
    SYMPTOMS

; pathologic conditions affecting

    hematopoietic marrow
    MICROSCOPIC

 typically result in

    increased signal intensity due to either accumulated lipid or water
    SYMPTOMS

. Because of its

    high fat content
    MICROSCOPIC

,

    yellow marrow
    MICROSCOPIC

 normally yields

    high signal intensity on phase-contrast images
    SYMPTOMS

, whereas abnormal conditions usually result in

    decreased phase-contrast signal intensity
    SYMPTOMS

 due to

    increased tissue water
    MICROSCOPIC

.

    Proton chemical shift imaging
    PARACLINICAL

 is likely to be a valuable supplement to standard

    magnetic resonance imaging techniques
    PARACLINICAL

 in the

    study of bone marrow
    PARACLINICAL

 in vivo.


Fat embolism and osteonecrosis.

Clinical and experimental data accumulated within the past 2 decades explain the relationship between fat embolism and osteonecrosis, which now appears to be more causal than coincidental. Evidence for fatty liver, coalescence of endogenous plasma lipoproteins, and/or disruption of depot or marrow fat, all resulting in continuous or intermittent fat embolism, is related to 13 different clinical conditions associated with osteonecrosis, most recently including pregnancy, carbon tetrachloride poisoning, and possibly Legg-Calvé-Perthes disease. Intraosseous fat embolism, then, appears to trigger a three-phase thrombotic process of focal intravascular coagulation that results in osteonecrosis.

Clinical and experimental data accumulated within the past 2 decades explain the relationship between

    fat embolism
    SYMPTOMS

 and

    osteonecrosis
    DIAGNOSIS

, which now appears to be more causal than coincidental. Evidence for

    fatty liver
    MICROSCOPIC

,

    coalescence of endogenous plasma lipoproteins
    MICROSCOPIC

, and/or

    disruption of depot or marrow fat
    MICROSCOPIC

, all resulting in

    continuous or intermittent fat embolism
    SYMPTOMS

, is related to 13 different clinical conditions associated with

    osteonecrosis
    DIAGNOSIS

, most recently including

    pregnancy
    DIAGNOSIS

,

    carbon tetrachloride poisoning
    DIAGNOSIS

, and possibly

    Legg-Calvé-Perthes disease
    DIAGNOSIS

.

    Intraosseous fat embolism
    SYMPTOMS

, then, appears to trigger a

    three-phase thrombotic process of focal intravascular coagulation
    SYMPTOMS

 that results in

    osteonecrosis
    DIAGNOSIS

.

osteonecrosis
osteonecrosis
pregnancy
carbon tetrachloride poisoning
Legg-Calvé-Perthes disease
osteonecrosis


Association of Gaucher's disease and lymphoid malignancy in 2 children.

2 cases of acute lymphoblastic leukaemia (ALL) of childhood in association with Gaucher's Disease (GD) are presented, which are the first to be described. One of them is a common non-B non-T cell ALL and the other is at T-cell ALL. The association of GD with benign and malignant B-cell proliferation has recently been described. It is suggested that chronic stimulation of the immune system by the accumulated glucocerebroside may predispose to B cell proliferation.

2 cases of

    acute lymphoblastic leukaemia (ALL) of childhood
    DIAGNOSIS

 in association with

    Gaucher's Disease (GD)
    DIAGNOSIS

 are presented, which are the first to be described. One of them is a

    common non-B non-T cell ALL
    DIAGNOSIS

 and the other is

    at T-cell ALL
    DIAGNOSIS

. The association of

    GD
    DIAGNOSIS

 with

    benign and malignant B-cell proliferation
    MICROSCOPIC

 has recently been described. It is suggested that

    chronic stimulation of the immune system by the accumulated glucocerebroside
    MICROSCOPIC

 may predispose to

    B cell proliferation
    MICROSCOPIC

.


Assay of glucocerebrosidase using a fluorescent analogue of glucocerebroside for the diagnosis of Gaucher disease.

For the diagnosis of homozygotes and heterozygotes of Gaucher disease, glucocerebrosidase (glucocerebroside beta-D-glucoside glucohydrolase, EC 3.2.1.45) activity in lymphocytes was measured using a fluorescent analogue of glucocerebroside, 1-0-glucosyl-2-N-(dimethylaminonaphthalene-5-sulfonyl)-sphingosine as substrate. The activity in lymphocytes from homozygotes of Gaucher disease was found to be reduced markedly. This method is proved to be simple, sensitive, and specific as an assay of glucocerebrosidase activity for the diagnosis of Gaucher disease.

For the diagnosis of homozygotes and

    heterozygotes
    GENETICS

 of

    Gaucher disease
    DIAGNOSIS

,

    glucocerebrosidase (glucocerebroside beta-D-glucoside glucohydrolase, EC 3.2.1.45) activity in lymphocytes
    BIOCHEMICAL

 was measured using a

    fluorescent analogue of glucocerebroside, 1-0-glucosyl-2-N-(dimethylaminonaphthalene-5-sulfonyl)-sphingosine
    MICROSCOPIC

 as substrate.

    The activity in lymphocytes
    BIOCHEMICAL

 from homozygotes of

    Gaucher disease
    DIAGNOSIS

 was found

    to be reduced markedly
    BIOCHEMICAL

. This method is proved to be simple, sensitive, and specific as an

    assay of glucocerebrosidase activity
    PARACLINICAL

 for the diagnosis of

    Gaucher disease
    DIAGNOSIS

.

Gaucher disease
Gaucher disease
Gaucher disease


Skeletal complications of Gaucher disease.

Gaucher disease is a collection of related disorders of sphingolipid catabolism caused by the deficiency of a specific beta-glucosidase. The inefficiency of this enzyme, glucocerebrosidase, to degrade its natural substrate leads to the accumulation of the complex lipid glucocerebroside in tissue macrophages. The pathogenesis of the disease is, as yet, poorly understood. The manifestations of the disease are protean with hepatosplenomegaly and bone deterioration frequently the predominating signs. The disease most frequently causes disability because of its effects on the skeleton. This review seeks to summarize the current clinical understanding of these complications. Experience with 327 patients reveals that the bone disease in this disorder is extremely variable. The severity of the problems range from asymptomatic persons with neither radiographic, scintigraphic, nor histologic evidence of bone involvement to those whose skeleton is completely devastated by a process of osteopenia, osteonecrosis, and osteosclerosis. These severely affected individuals show the most bizarre deformities in their bones and are subject to pathologic fracture. Most patients fortunately, are less profoundly affected, but many are plagued by bone pain of an arthritic nature or by an acute prostrating bone crisis probably best described as a bone infarction. The accepted etiology that these crises are a result of vascular compromise produced by occlusion of vessels by Gaucher cells is not supported by scintigraphic or histologic studies. Moreover, the vascular hypothesis does not explain the variety of lesions of the skeleton seen in this multifocal bone disease. Preliminary metabolic and endocrinologic studies suggest that this is not a systemic disorder of metabolism which affects bone uniformly. On the contrary, the lesions are multiple and localized, and sometimes much of the skeleton is preserved. These observations suggest that bone is affected because of collections of Gaucher cells scattered throughout its substance and may be the result of a toxic process around these foci. Alternatively, the storage of glucocerebroside in tissue macrophages may disturb the generation of competent osteoclasts and thus result in a failure to maintain a healthy skeleton. Further research is needed to delineate the pathogenesis of this disorder before any effective therapy can be developed.

    Gaucher disease
    DIAGNOSIS

 is a collection of related

    disorders of sphingolipid catabolism
    DIAGNOSIS

 caused by the

    deficiency of a specific beta-glucosidase
    BIOCHEMICAL

. The

    inefficiency of this enzyme, glucocerebrosidase, to degrade its natural substrate
    BIOCHEMICAL

 leads to the

    accumulation of the complex lipid glucocerebroside in tissue macrophages
    MICROSCOPIC

. The pathogenesis of the disease is, as yet, poorly understood. The manifestations of the disease are

    protean
    SYMPTOMS

 with

    hepatosplenomegaly
    SYMPTOMS

 and

    bone deterioration
    SYMPTOMS

 frequently the predominating signs. The disease most frequently causes

    disability
    SYMPTOMS

 because of its

    effects on the skeleton
    SYMPTOMS

. This review seeks to summarize the current clinical understanding of these complications. Experience with 327 patients reveals that the

    bone disease
    DIAGNOSIS

 in this disorder is extremely variable. The severity of the problems range from

    asymptomatic
    NEG_FINDINGS

 persons with

    neither radiographic, scintigraphic, nor histologic evidence of bone involvement
    NEG_FINDINGS

 to those whose

    skeleton is completely devastated by a process of osteopenia
    SYMPTOMS

,

    osteonecrosis
    SYMPTOMS

, and

    osteosclerosis
    SYMPTOMS

. These severely affected individuals show the

    most bizarre deformities in their bones
    SYMPTOMS

 and are subject to

    pathologic fracture
    SYMPTOMS

. Most patients fortunately, are less profoundly affected, but many are plagued by

    bone pain of an arthritic nature
    SYMPTOMS

 or by an

    acute prostrating bone crisis
    SYMPTOMS

 probably best described as a

    bone infarction
    SYMPTOMS

. The accepted etiology that these

    crises
    SYMPTOMS

 are a result of

    vascular compromise produced by occlusion of vessels by Gaucher cells
    SYMPTOMS

 is not supported by

    scintigraphic or histologic studies
    PARACLINICAL

. Moreover, the

    vascular hypothesis does not
    NEG_FINDINGS

 explain the

    variety of lesions of the skeleton
    SYMPTOMS

 seen in this

    multifocal bone disease
    DIAGNOSIS

.

    Preliminary metabolic and endocrinologic studies
    PARACLINICAL

 suggest that this is not a

    systemic disorder of metabolism which affects bone uniformly
    NEG_FINDINGS

. On the contrary, the

    lesions are multiple and localized
    SYMPTOMS

, and sometimes

    much of the skeleton is preserved
    SYMPTOMS

. These observations suggest that bone is affected because of

    collections of Gaucher cells scattered throughout its substance
    MICROSCOPIC

 and may be the result of a

    toxic process around these foci
    MICROSCOPIC

. Alternatively, the

    storage of glucocerebroside in tissue macrophages
    MICROSCOPIC

 may

    disturb the generation of competent osteoclasts
    NEG_FINDINGS

 and thus result in a

    failure to maintain a healthy skeleton
    NEG_FINDINGS

. Further research is needed to delineate the pathogenesis of this disorder before any effective therapy can be developed.

Gaucher disease
disorders of sphingolipid catabolism
bone disease
multifocal bone disease


Partial splenectomy in children with Gaucher's disease.

Because of hypersplenism and mechanical problems, partial splenectomy was performed in four children with Gaucher's disease. Subsequently, one of the patients underwent a total splenectomy due to bleeding from the remnant of the spleen. At the follow-up of the other three patients, an isotope scan showed that the remaining spleen was functioning well.

Because of

    hypersplenism
    BIOCHEMICAL

 and

    mechanical problems
    SYMPTOMS

,

    partial splenectomy
    MEDICATION

 was performed in four

    children
    AGE

 with

    Gaucher's disease
    DIAGNOSIS

. Subsequently, one of the patients underwent a

    total splenectomy
    MEDICATION

 due to

    bleeding from the remnant of the spleen
    SYMPTOMS

. At the

    follow-up
    PARACLINICAL

 of the other three patients, an

    isotope scan
    PARACLINICAL

 showed that

    the remaining spleen was functioning well
    SYMPTOMS

.


Glycosphingolipid studies of visceral tissues and brain from type 1 Gaucher disease variants.

Glucosylceramide and glucosylsphingosine isolated from spleen, liver and brain were quantitated and characterized in two unrelated patients with Gaucher disease, neither of whom had clinical or neuropathologic evidence of neuronal involvement. Visceral glucosylceramide accumulation did not differ in the two patients. Hepatic glucosylsphingosine content was 2-fold greater in a young severely affected 3-year-old American Black patient compared to that in a 56-year-old Ashkenazi Jewish patient. In contrast, significant differences in glycosphingolipid content and composition were observed in the brains of these two cases. Cerebral and cerebellar cortical glucosylceramide accumulated to a greater extent (3-fold) in the severely affected 3-year-old patient compared to that in the older case. The compositions of the acyl and sphingosyl base residues of glucosylceramide in the cerebral and cerebellar cortices from the Ashkenazi Jewish patient were similar to those in normal individuals. In comparison, the gray matter glucosylceramide in the severely affected patient had increased percentages of stearic acid (18:0) and eicosasphingenine (d20:1), suggesting that the accumulated substrate was derived from the brain ganglioside pool. Glucosylsphingosine was found in large amounts only in cerebral and cerebellar cortices from the severely affected patient. The glycolipid content and composition in this patient was similar to that found in the Norrbottnian (Type 3) form of Gaucher disease. The differences in glucosylceramide acyl and sphingosyl base composition in gray matter from the severely affected patient and that in the Ashkenazi Jewish patient suggested that the accumulated substrates were metabolized differently by the residual enzymes in each case.(ABSTRACT TRUNCATED AT 250 WORDS)

    Glucosylceramide and glucosylsphingosine isolated from spleen, liver and brain
    MICROSCOPIC

 were quantitated and characterized in two unrelated patients with

    Gaucher disease
    DIAGNOSIS

, neither of whom had

    clinical or neuropathologic evidence of neuronal involvement
    NEG_FINDINGS

.

    Visceral glucosylceramide accumulation
    MICROSCOPIC

 did not differ in the two patients.

    Hepatic glucosylsphingosine content was 2-fold greater
    MICROSCOPIC

 in a

    young
    AGE

 severely affected

    3-year-old
    AGE

    American Black
    ETHNICITY

 patient compared to that in a

    56-year-old
    AGE

    Ashkenazi Jewish
    ETHNICITY

 patient. In contrast, significant differences

    in glycosphingolipid content and composition
    MICROSCOPIC

 were observed in the brains of these two cases.

    Cerebral and cerebellar cortical glucosylceramide accumulated to a greater extent (3-fold)
    MICROSCOPIC

 in the severely affected

    3-year-old
    AGE

 patient compared to that in the older case. The

    compositions of the acyl and sphingosyl base residues of glucosylceramide in the cerebral and cerebellar cortices
    MICROSCOPIC

 from the

    Ashkenazi Jewish
    ETHNICITY

 patient were similar to those in normal individuals. In comparison,

    the gray matter glucosylceramide in
    MICROSCOPIC

 the severely affected patient

    had increased percentages of stearic acid (18:0) and eicosasphingenine (d20:1)
    MICROSCOPIC

, suggesting that the

    accumulated substrate was derived from the brain ganglioside pool
    MICROSCOPIC

.

    Glucosylsphingosine was found in large amounts only in cerebral and cerebellar cortices
    MICROSCOPIC

 from the severely affected patient. The

    glycolipid content and composition
    MICROSCOPIC

 in this patient was similar to that found in the

    Norrbottnian (Type 3) form of Gaucher disease
    DIAGNOSIS

. The differences in

    glucosylceramide acyl and sphingosyl base composition in gray matter
    MICROSCOPIC

 from the severely affected patient and that in the

    Ashkenazi Jewish
    ETHNICITY

 patient suggested that the accumulated substrates were metabolized differently by the residual enzymes in each case.(ABSTRACT TRUNCATED AT 250 WORDS)

American Black
Ashkenazi Jewish
Ashkenazi Jewish
Ashkenazi Jewish


Gaucher's disease: a case history with extensive lipid storage in the brain.

Patients with acute infantile or type II neuropathic Gaucher's disease demonstrate neurologic deficits that are seemingly greater than the extent of the central nervous system involvement found at autopsy. Examination of the brain of an affected child shows widespread deposition of lipid in a pattern not recognized heretofore. Based on these observations, the authors hypothesize that widespread deposition of the Gaucher glucocerebroside elicits a mild tissue response, which functionally becomes highly significant.

Patients with

    acute infantile or type II neuropathic Gaucher's disease
    DIAGNOSIS

 demonstrate

    neurologic deficits
    SYMPTOMS

 that are seemingly greater than the

    extent of the central nervous system involvement
    SYMPTOMS

 found at

    autopsy
    PARACLINICAL

.

    Examination of the brain
    PARACLINICAL

 of an affected

    child
    AGE

 shows

    widespread deposition of lipid in a pattern
    MICROSCOPIC

 not recognized heretofore. Based on these observations, the authors hypothesize that

    widespread deposition of the Gaucher glucocerebroside
    MICROSCOPIC

 elicits a

    mild tissue response
    SYMPTOMS

, which

    functionally becomes highly significant
    SYMPTOMS

.


Gaucher's disease affecting the mandible.

A case of Gaucher's disease affecting the left body of the mandible is presented. Dentists can recognize this uncommon disease through the medical history of the patient, the presence of characteristic Gaucher cells on biopsy of the lesion, and decreased serum levels of the enzyme glucocerebrosidase.

A case of

    Gaucher's disease affecting the left body of the mandible
    DIAGNOSIS

 is presented. Dentists can recognize this uncommon disease through the medical history of the patient, the

    presence of characteristic Gaucher cells on biopsy of the lesion
    MICROSCOPIC

, and

    decreased serum levels of the enzyme glucocerebrosidase
    BIOCHEMICAL

.


Neurological involvement in type 1 (adult) Gaucher's disease.

A case of type 1 (adult) Gaucher's disease with a late onset tapeto-retinal degeneration and an initially dopamine responsive extrapyramidal syndrome is described. The literature reporting neurological involvement in type 1 Gaucher's disease is reviewed, and it is concluded that the absence of symptoms and signs of nervous system involvement cannot be used as the sole basis for the classification of this type of Gaucher's disease.

A case of

    type 1 (adult) Gaucher's disease
    DIAGNOSIS

 with a

    late onset tapeto-retinal degeneration
    SYMPTOMS

 and an

    initially dopamine responsive extrapyramidal syndrome
    NEG_FINDINGS

 is described. The literature reporting

    neurological involvement
    SYMPTOMS

 in

    type 1 Gaucher's disease
    DIAGNOSIS

 is reviewed, and it is concluded that the

    absence of symptoms and signs of nervous system involvement
    NEG_FINDINGS

 cannot be used as the sole basis for the classification of this type of

    Gaucher's disease
    DIAGNOSIS

.

type 1 (adult) Gaucher's disease
type 1 Gaucher's disease
Gaucher's disease

late onset tapeto-retinal degeneration
neurological involvement


New ocular findings in Gaucher's disease: a report of two brothers.

White deposits in the peripheral corneal endothelium, chamber angle and pupil margin are new findings in 1 of a sibship of 2 males affected by Gaucher's disease.

    White deposits in the peripheral corneal endothelium, chamber angle and pupil margin
    SYMPTOMS

 are new findings in 1 of a

    sibship of 2 males
    FAMILY

    affected by Gaucher's disease
    FAMILY

.


Unusual echocardiographic pattern in Gaucher's disease.

Described in this paper is a 73-year-old Ashkenazi Jew affected with adult type 1 (nonneuronopathic form) Gaucher's disease. This was diagnosed at the age of 46 during an investigation of hepatosplenomegaly. No other members of his family were known to be affected with this disorder. The patient has been periodically examined at our Institute and has been free of all cardiopulmonary symptoms. This description emphasizes his echocardiographic pattern which revealed left ventricular hypertrophy, a septal muscular hump, and an extended area of apical akinesis. Myocardial involvement in Gaucher's disease has seldom been reported in the past.

Described in this paper is a

    73-year-old
    AGE

    Ashkenazi Jew
    ETHNICITY

 affected with

    adult type 1 (nonneuronopathic form) Gaucher's disease
    DIAGNOSIS

. This was diagnosed at the

    age of 46
    AGE

 during an investigation of

    hepatosplenomegaly
    SYMPTOMS

.

    No other members of his family were known to be affected with this disorder
    FAMILY

. The patient has been periodically examined at our Institute and has been

    free of all cardiopulmonary symptoms
    NEG_FINDINGS

. This description emphasizes his echocardiographic pattern which revealed

    left ventricular hypertrophy
    SYMPTOMS

,

    a septal muscular hump
    SYMPTOMS

, and an

    extended area of apical akinesis
    SYMPTOMS

.

    Myocardial involvement
    SYMPTOMS

 in

    Gaucher's disease
    DIAGNOSIS

 has seldom been reported in the past.

hepatosplenomegaly
left ventricular hypertrophy
a septal muscular hump
extended area of apical akinesis
Myocardial involvement


[Gaucher's disease combined with congenital developmental defects of the urinary system].

Two cases of Gaucher's disease of the juvenile type are described, in a boy of 1 year and 7 months and in a girl of 8 years. The juvenile type of Gaucher's disease is documented by detection in the internal organs of typical Gaucher's cells formed mainly of histiocytes and macrophages, PAS-positive and weakly positive with Sudan III, and by the absence of the brain gangliocytes impairments. The peculiarity of these cases consists in the combination of glucocerebroside with congenital developmental defects of the urinary system: in one case with bilateral megaureter and hydronephrosis and in the second one with developmental defect of the renal arteries and bilateral cystic renal dysplasia.

Two cases of

    Gaucher's disease of the juvenile type
    DIAGNOSIS

 are described, in a

    boy
    GENDER

    of 1 year and 7 months
    AGE

 and in a

    girl
    GENDER

    of 8 years
    AGE

. The

    juvenile type of Gaucher's disease
    DIAGNOSIS

 is documented by

    detection in the internal organs of typical Gaucher's cells formed mainly of histiocytes and macrophages, PAS-positive and weakly positive with Sudan III
    MICROSCOPIC

, and by the

    absence of the brain gangliocytes impairments
    NEG_FINDINGS

. The peculiarity of these cases consists in the

    combination of glucocerebroside
    MICROSCOPIC

 with

    congenital developmental defects of the urinary system
    SYMPTOMS

: in one case with

    bilateral megaureter
    SYMPTOMS

 and

    hydronephrosis
    SYMPTOMS

 and in the second one with

    developmental defect of the renal arteries
    SYMPTOMS

 and

    bilateral cystic renal dysplasia
    SYMPTOMS

.

Gaucher's disease of the juvenile type
juvenile type of Gaucher's disease


Vascular involvement in type 3 neuronopathic Gaucher's disease.

A 6 3/4-year-old boy with neuronopathic Gaucher's disease died unexpectedly. Autopsy demonstrated unusual vascular findings with the presence of Gaucher's cells and intimal-medial fibrosis in the ascending aorta and widespread acute hemorrhagic necrosis of the left ventricular myocardium. The combination of eccentric, intimal fibrosis of coronary arteries, left ventricular hypertrophy, pulmonary involvement, and anemia probably accounted for this child's death.

A

    6 3/4-year-old
    AGE

    boy
    GENDER

 with

    neuronopathic Gaucher's disease
    DIAGNOSIS

    died
    SYMPTOMS

 unexpectedly.

    Autopsy
    PARACLINICAL

 demonstrated

    unusual vascular findings
    SYMPTOMS

 with the

    presence of Gaucher's cells and intimal-medial fibrosis in the ascending aorta
    MICROSCOPIC

 and

    widespread acute hemorrhagic necrosis of the left ventricular myocardium
    SYMPTOMS

. The combination of

    eccentric, intimal fibrosis of coronary arteries
    SYMPTOMS

,

    left ventricular hypertrophy
    SYMPTOMS

,

    pulmonary involvement
    SYMPTOMS

, and

    anemia
    BIOCHEMICAL

 probably accounted for this

    child
    AGE

's

    death
    SYMPTOMS

.


Immune thrombocytopenia and Gaucher's disease.

A 35-year-old Ashkenazi woman with Gaucher's disease was evaluated for persistent thrombocytopenia. The diagnosis of Gaucher's disease was made by bone marrow aspiration and confirmed by the determination of glucocerebrosidase levels in leukocytes and cultured skin fibroblasts. Studies of platelet-associated IgG and in vivo platelet survival demonstrated immune-mediated destruction of platelets consistent with immune thrombocytopenic purpura. A trial of prednisone had no effect on the platelet count. Total splenectomy resulted in a complete and prolonged remission. The clinical implications of Gaucher's disease and concurrent immune thrombocytopenic purpura are discussed.

A

    35-year-old
    AGE

    Ashkenazi
    ETHNICITY

    woman
    GENDER

 with

    Gaucher's disease
    DIAGNOSIS

 was evaluated for

    persistent thrombocytopenia
    BIOCHEMICAL

. The diagnosis of

    Gaucher's disease
    DIAGNOSIS

 was made by

    bone marrow aspiration
    PARACLINICAL

 and confirmed by the determination of

    glucocerebrosidase levels in leukocytes and cultured skin fibroblasts
    MICROSCOPIC

.

    Studies of platelet-associated IgG
    BIOCHEMICAL

 and

    in vivo platelet survival
    PARACLINICAL

 demonstrated

    immune-mediated destruction of platelets consistent with immune thrombocytopenic purpura
    MICROSCOPIC

. A

    trial of prednisone had no effect on the platelet count
    NEG_FINDINGS

.

    Total splenectomy
    MEDICATION

 resulted in a

    complete and prolonged remission
    SYMPTOMS

. The clinical implications of

    Gaucher's disease
    DIAGNOSIS

 and

    concurrent immune thrombocytopenic purpura
    DIAGNOSIS

 are discussed.

persistent thrombocytopenia
Studies of platelet-associated IgG


Hydrops fetalis associated with Gaucher disease.

The rare association of hydrops fetalis with acute neuropathic Gaucher disease, diagnosed at autopsy, is described. Mechanisms for the fetal edema in this case are discussed. Unusual medial calcification of the aorta was present; and although its etiology is unknown, a possible relationship to Gaucher disease is suggested.

The rare association of

    hydrops fetalis
    DIAGNOSIS

 with

    acute neuropathic Gaucher disease
    DIAGNOSIS

, diagnosed at

    autopsy
    PARACLINICAL

, is described. Mechanisms for the

    fetal edema
    SYMPTOMS

 in this case are discussed.

    Unusual medial calcification of the aorta
    SYMPTOMS

 was present; and although its etiology is unknown, a possible relationship to

    Gaucher disease
    DIAGNOSIS

 is suggested.

hydrops fetalis
acute neuropathic Gaucher disease
Gaucher disease


Gaucher's disease in a black child in South Africa. A case report.

A 7-year-old Black boy presented with massive splenomegaly and a tendency to haemorrhage due to type 1 Gaucher's disease. After splenectomy he became asymptomatic and the haematological parameters returned to normal. Although type 1 Gaucher's disease has been described in adult Blacks, it has not been reported previously in a Black child in southern Africa.

A

    7-year-old
    AGE

    Black
    ETHNICITY

    boy
    GENDER

 presented with

    massive splenomegaly
    SYMPTOMS

 and a

    tendency to haemorrhage
    SYMPTOMS

 due to

    type 1 Gaucher's disease
    DIAGNOSIS

. After

    splenectomy
    MEDICATION

 he became

    asymptomatic
    NEG_FINDINGS

 and

    the haematological parameters returned to normal
    BIOCHEMICAL

. Although

    type 1 Gaucher's disease
    DIAGNOSIS

 has been described in

    adult
    AGE

    Blacks
    ETHNICITY

, it has not been reported previously in a

    Black child
    AGE

 in

    southern Africa
    ETHNICITY

.

massive splenomegaly
tendency to haemorrhage

type 1 Gaucher's disease
type 1 Gaucher's disease


Gaucher's disease and chronic lymphocytic leukemia. Possible pathogenetic link between Gaucher's disease and B-cell proliferations?

The authors report a case of Gaucher's disease with chronic lymphocytic leukemia. The diagnosis of Gaucher's disease was confirmed by electron microscopy and glucocerebrosidase assay. There may be a pathogenetic link between Gaucher's disease and B-cell proliferation.

The authors report a case of

    Gaucher's disease
    DIAGNOSIS

 with

    chronic lymphocytic leukemia
    DIAGNOSIS

. The diagnosis of

    Gaucher's disease
    DIAGNOSIS

 was confirmed by

    electron microscopy
    PARACLINICAL

 and

    glucocerebrosidase assay
    PARACLINICAL

. There may be a pathogenetic link between

    Gaucher's disease
    DIAGNOSIS

 and

    B-cell proliferation
    MICROSCOPIC

.

Gaucher's disease
chronic lymphocytic leukemia
Gaucher's disease
Gaucher's disease


Bone-marrow transplantation in severe Gaucher's disease.

We performed allogeneic bone-marrow transplantation of normal cells in an eight-year-old patient with Type 3 Gaucher's disease in an attempt to alter his progressive deterioration. The procedure resulted in complete engraftment of the enzymatically normal donor cells. Donor monocyte precursors were present in the circulation of the recipient by 28 days after transplantation. Post-transplantation beta-glucocerebrosidase activity in mononuclear white cells in peripheral blood exceeded normal levels. Despite these early results no change in Gaucher's-cell infiltration of the bone marrow was noted for at least 111 days, and Gaucher's cells persisted in the marrow for at least 274 days. The plasma glucocerebroside concentration ultimately returned to normal. During the post-transplantation course, until the patient died from an episode of sepsis, there was no important change in his clinical status. However, this case demonstrates that the enzymatic abnormality in hematopoietic cells in Gaucher's disease is correctable by bone-marrow transplantation, leading to normalization of plasma levels of glucocerebroside. We observed the long survival of Gaucher's cells, which was consistent with the lack of clinical improvement. Intervention might have been more effective earlier in the course of the disease.

We performed

    allogeneic bone-marrow transplantation of normal cells
    MEDICATION

 in an

    eight-year-old
    AGE

 patient with

    Type 3 Gaucher's disease
    DIAGNOSIS

 in an attempt to alter his

    progressive deterioration
    SYMPTOMS

. The procedure resulted in

    complete engraftment of the enzymatically normal donor cells
    MICROSCOPIC

.

    Donor monocyte precursors were present in the circulation of the recipient
    MICROSCOPIC

 by 28 days after

    transplantation
    MEDICATION

.

    Post-
    BIOCHEMICAL

transplantation

    beta-glucocerebrosidase activity in mononuclear white cells in peripheral blood exceeded normal levels
    BIOCHEMICAL

. Despite these early results

    no change in Gaucher's-cell infiltration of the bone marrow was noted for at least 111 days
    NEG_FINDINGS

, and

    Gaucher's cells persisted in the marrow for at least 274 days
    MICROSCOPIC

.

    The plasma glucocerebroside concentration ultimately returned to normal
    BIOCHEMICAL

. During the

    post-transplantation
    MEDICATION

 course, until the patient

    died from an episode of sepsis
    SYMPTOMS

, there was

    no important change in his clinical status
    NEG_FINDINGS

. However, this case demonstrates that the

    enzymatic abnormality in hematopoietic cells
    MICROSCOPIC

 in

    Gaucher's disease
    DIAGNOSIS

 is correctable by

    bone-marrow transplantation
    MEDICATION

, leading to

    normalization of plasma levels of glucocerebroside
    BIOCHEMICAL

. We observed the

    long survival of Gaucher's cells
    MICROSCOPIC

, which was consistent with the

    lack of clinical improvement
    NEG_FINDINGS

. Intervention might have been more effective earlier in the course of the disease.

Type 3 Gaucher's disease
Gaucher's disease

progressive deterioration
died from an episode of sepsis


Spinal cord compression secondary to Gaucher's disease.

A case of compression of the spinal cord and cauda equina secondary to collapse of the T-12 and L-3 vertebral bodies in a patient with type 1 Gaucher's disease is presented. Decompressive laminectomies were done at both the T-12 and L-3 levels with moderate improvement of the patient's neurologic findings. Histologic examinations confirmed the presence of Gaucher's cells in the bone. Review of the literature revealed only one previous report.

A case of

    compression of the spinal cord and cauda equina
    SYMPTOMS

 secondary to

    collapse of the T-12 and L-3 vertebral bodies
    SYMPTOMS

 in a patient with

    type 1 Gaucher's disease
    DIAGNOSIS

 is presented.

    Decompressive laminectomies were done at both the T-12 and L-3 levels
    MEDICATION

 with

    moderate improvement of the patient's neurologic findings
    SYMPTOMS

.

    Histologic examinations
    PARACLINICAL

 confirmed the

    presence of Gaucher's cells in the bone
    MICROSCOPIC

. Review of the literature revealed only one previous report.


Correlating auditory evoked and brainstem histologic abnormalities in infantile Gaucher's disease.

In an infant with Gaucher's disease, brainstem auditory evoked responses were abnormal on three separate occasions. Only waves I and II were typically present at standard intensity settings, although a third peak was elicited at 88 dB. Histologic studies demonstrated absence of neurons in the cochlear nuclei and a hypoplastic superior olivary complex. This neurophysiologic-pathologic correlation supports contentions that both brainstem auditory evoked response (BAER) waves I and II arise from the auditory nerve and that it may be capable of generating additional peaks.

In an

    infant
    AGE

 with

    Gaucher's disease
    DIAGNOSIS

,

    brainstem auditory evoked responses were abnormal
    SYMPTOMS

 on three separate occasions. Only

    waves I and II
    SYMPTOMS

 were typically present at standard intensity settings, although a third peak was elicited at 88 dB.

    Histologic studies
    PARACLINICAL

 demonstrated

    absence of neurons in the cochlear nuclei
    SYMPTOMS

 and a

    hypoplastic superior olivary complex
    SYMPTOMS

. This neurophysiologic-pathologic correlation supports contentions that both brainstem auditory evoked response (BAER) waves I and II arise from the auditory nerve and that it may be capable of generating additional peaks.


Congenital ascites as a presenting sign of lysosomal storage disease.

Neonatal ascites is usually attributed to hematologic, genitourinary, gastrointestinal tract, or congenital heart disease. When these lesions have been excluded, metabolic storage disorders should be considered in the differential diagnosis. We report eight cases of neonatal ascites associated with different types of lysosomal storage disease: infantile sialidosis, Salla disease, GM1 gangliosidosis, and Gaucher disease. In each case there was a history of sibling of perinatal death resulting from the disease. In three cases the diagnosis of ascites was made in utero by ultrasound examination. These diseases are characterized by excretion in the fetal urine of abnormal catabolic products or by measurement of decreased activity of specific lysosomal hydrolases in cultured amniocytes. Thin-layer chromatography of the oligosaccharides in amniotic fluid may be indicated when a diagnosis of persistent fetal ascites has been established.

    Neonatal ascites
    SYMPTOMS

 is usually attributed to

    hematologic
    DIAGNOSIS

,

    genitourinary, gastrointestinal tract
    DIAGNOSIS

, or

    congenital heart disease
    DIAGNOSIS

. When these lesions have been excluded,

    metabolic storage disorders
    DIAGNOSIS

 should be considered in the

    differential diagnosis
    PARACLINICAL

. We report eight cases of

    neonatal
    AGE

    ascites
    DIAGNOSIS

 associated with different types of

    lysosomal storage disease
    DIAGNOSIS

:

    infantile sialidosis
    DIAGNOSIS

,

    Salla disease
    DIAGNOSIS

,

    GM1 gangliosidosis
    DIAGNOSIS

, and

    Gaucher disease
    DIAGNOSIS

. In each case there was a

    history of sibling of perinatal death resulting from the disease
    FAMILY

. In three cases the diagnosis of

    ascites
    DIAGNOSIS

 was made in

    utero
    AGE

 by

    ultrasound examination
    PARACLINICAL

. These diseases are characterized by

    excretion in the fetal urine of abnormal catabolic products
    BIOCHEMICAL

 or by

    measurement of decreased activity of specific lysosomal hydrolases in cultured amniocytes
    BIOCHEMICAL

.

    Thin-layer chromatography of the oligosaccharides in amniotic fluid
    PARACLINICAL

 may be indicated when a diagnosis of

    persistent fetal ascites
    SYMPTOMS

 has been established.

Neonatal ascites
persistent fetal ascites

hematologic
genitourinary, gastrointestinal tract
congenital heart disease
metabolic storage disorders
ascites
lysosomal storage disease
infantile sialidosis
Salla disease
GM1 gangliosidosis
Gaucher disease
ascites


Gaucher's disease: unexpected diagnosis in three patients over seventy years old.

Gaucher's disease is usually diagnosed in the first or second decade of life with the appearance of bone pains, splenomegaly and hemorrhagic manifestations due to thrombocytopenia. When the hematological parameters are preserved and the enlarged spleen not evident until late in life, patients are rarely identified as having Gaucher's disease and the diagnosis is based only on the presence of Gaucher's cells in bone marrow. We present here three cases of elderly patients aged 81, 73 and 72 years in whom the disease was a surprise finding of bone marrow examination.

    Gaucher's disease
    DIAGNOSIS

 is usually diagnosed in the

    first or second decade of life
    AGE

 with the appearance of

    bone pains
    SYMPTOMS

,

    splenomegaly
    SYMPTOMS

 and

    hemorrhagic manifestations
    SYMPTOMS

 due to

    thrombocytopenia
    BIOCHEMICAL

. When the

    hematological parameters are preserved
    BIOCHEMICAL

 and the

    enlarged spleen not evident
    SYMPTOMS

 until

    late in life
    AGE

, patients are rarely identified as having

    Gaucher's disease
    DIAGNOSIS

 and the diagnosis is based only on the

    presence of Gaucher's cells in bone marrow
    MICROSCOPIC

. We present here three cases of

    elderly
    AGE

 patients

    aged 81, 73 and 72 years
    AGE

 in whom the disease was a surprise finding of

    bone marrow examination
    PARACLINICAL

.

bone pains
splenomegaly
hemorrhagic manifestations
enlarged spleen not evident

thrombocytopenia
hematological parameters are preserved


An adult form of Gaucher's disease with a huge tumour formation of the right tibia.

A case of adult, chronic or non-neuropathic, Gaucher's disease is presented. Severe bony changes, particularly involving the lower limbs developed after a splenectomy had been carried out. Our patient had all the orthopaedic complications of Gaucher's disease. Further, a huge tumour was present in the right tibia caused by the proliferation of Gaucher cells. This feature may be unique but pseudotumour should be listed in the possible orthopaedic complications of Gaucher's disease. The patient was bedridden, but was able to use a wheelchair after his leg was amputated.

A case of

    adult
    AGE

,

    chronic or non-neuropathic, Gaucher's disease
    DIAGNOSIS

 is presented.

    Severe bony changes, particularly involving the lower limbs
    SYMPTOMS

 developed after a

    splenectomy
    MEDICATION

 had been carried out. Our patient had all the

    orthopaedic complications
    SYMPTOMS

 of

    Gaucher's disease
    DIAGNOSIS

. Further, a

    huge tumour was present in the right tibia
    SYMPTOMS

 caused by the

    proliferation of Gaucher cells
    MICROSCOPIC

. This feature may be unique but

    pseudotumour
    DIAGNOSIS

 should be listed in the possible

    orthopaedic complications
    SYMPTOMS

 of

    Gaucher's disease
    DIAGNOSIS

. The patient was

    bedridden
    NEG_FINDINGS

, but was

    able to use a wheelchair
    MEDICATION

 after his

    leg was amputated
    MEDICATION

.

splenectomy
able to use a wheelchair
leg was amputated