[Adult Gaucher's disease with pulmonary involvement].

Gaucher's disease is an autosomal recessive disorder caused by deficiency of the enzyme glucocerebrosidase with accumulation of glucocerebroside in the reticuloendothelial system. Affection of the lungs by this disease is extremely rare. When Gaucher cells infiltrate the lung, fibrosis may result. We describe a case with adult type Gaucher's disease who, besides affection of liver, spleen and bone marrow, had severe pulmonary involvement with extensive interstitial fibrosis, increased pulmonary vascular resistance, and pronounced reduction in diffusion capacity.

    Gaucher's disease
    DIAGNOSIS

 is an

    autosomal recessive disorder
    GENETICS

 caused by

    deficiency of the enzyme glucocerebrosidase
    BIOCHEMICAL

 with

    accumulation of glucocerebroside in the reticuloendothelial system
    MICROSCOPIC

. Affection of the lungs by this disease is extremely rare. When

    Gaucher cells infiltrate the lung
    MICROSCOPIC

,

    fibrosis
    SYMPTOMS

 may result. We describe a case with

    adult type Gaucher's disease
    DIAGNOSIS

 who, besides

    affection of liver, spleen and bone marrow
    MICROSCOPIC

, had

    severe pulmonary involvement
    SYMPTOMS

 with

    extensive interstitial fibrosis
    SYMPTOMS

,

    increased pulmonary vascular resistance
    SYMPTOMS

, and

    pronounced reduction in diffusion capacity
    SYMPTOMS

.

Gaucher's disease
adult type Gaucher's disease


Enzyme replacement therapy for Gaucher disease.

Four patients with moderately severe type I Gaucher disease were treated with commercially available mannose terminated glucocerebrosidase (Ceredase; Genzyme, Boston, MA) for up to 13 months. The enzyme was administered at the rate of three to four times weekly at one fourth the total recommended dosage, greatly decreasing the cost. Marked regression of hepatomegaly and improvement in liver function tests, peripheral blood counts, and serum angiotensin-converting enzyme levels were documented. The two patients with pulmonary involvement manifested improvement in pulmonary function tests. Skeletal disease remained unchanged.

Four patients with

    moderately severe type I Gaucher disease
    DIAGNOSIS

 were

    treated with commercially available mannose terminated glucocerebrosidase (Ceredase;
    MEDICATION

 Genzyme, Boston, MA

    ) for up to 13 months
    MEDICATION

.

    The enzyme was administered at the rate of three to four times weekly at one fourth the total recommended dosage
    MEDICATION

, greatly decreasing the cost.

    Marked regression of hepatomegaly
    SYMPTOMS

 and

    improvement in liver function tests, peripheral blood counts, and serum angiotensin-converting enzyme levels
    BIOCHEMICAL

 were documented. The two patients with

    pulmonary involvement
    SYMPTOMS

 manifested

    improvement in pulmonary function tests
    SYMPTOMS

.

    Skeletal disease remained unchanged
    SYMPTOMS

.

Marked regression of hepatomegaly
pulmonary involvement
improvement in pulmonary function tests
Skeletal disease remained unchanged


Diagnosing osteomyelitis in Gaucher's disease. Observations on two cases.

Bone scans in two patients with Gaucher's disease were reported as consistent with Gaucher's-associated osseous crises. A bone-radiogallium subtraction study was also initially negative in each individual (although it later became positive in one). At surgery both patients were seen to have osteomyelitis. These two cases point out the difficulty in attempting to diagnose osteomyelitis in the presence of Gaucher's bone disease. A possible role for MRI in such instances was mentioned. Also noted was clinical reluctance to accept a diagnosis of osteomyelitis (positive bone-radiogallium subtraction study) in an afebrile Gaucher's patient.

    Bone scans
    PARACLINICAL

 in two patients with

    Gaucher's disease
    DIAGNOSIS

 were reported as consistent with

    Gaucher's-associated osseous crises
    DIAGNOSIS

.

    A bone-radiogallium subtraction study was also initially negative
    NEG_FINDINGS

 in each individual (although it later became positive in one). At

    surgery
    MEDICATION

 both patients were seen to have

    osteomyelitis
    DIAGNOSIS

. These two cases point out the difficulty in attempting to diagnose

    osteomyelitis
    DIAGNOSIS

 in the presence of

    Gaucher's bone disease
    DIAGNOSIS

. A possible role for

    MRI
    PARACLINICAL

 in such instances was mentioned. Also noted was

    clinical reluctance to accept a diagnosis of osteomyelitis (positive bone-radiogallium subtraction study)
    NEG_FINDINGS

 in an

    afebrile
    NEG_FINDINGS

    Gaucher's
    DIAGNOSIS

 patient.

Gaucher's disease
Gaucher's-associated osseous crises
osteomyelitis
osteomyelitis
Gaucher's bone disease
Gaucher's


Crisis in Gaucher disease simulating osteomyelitis: report of one case.

An 11-year-old boy with Gaucher disease developed acute bone pain of the left thigh, accompanied by fever and signs of inflammation. Initially he was treated as osteomyelitis with antibiotics. Cultures of blood and aspirate of a subperiosteal hematoma were negative for bacterial growth. Tc99m bone scan revealed relatively decreased uptake over the involved area, and the findings of magnetic resonance imaging were typical for Gaucher crisis. Although Ga 67 imaging was positive, the diagnosis of a bone pain crisis rather than an infection was made. Antibiotics were discontinued without sequelae. Differential diagnosis between Gaucher crisis and osteomyelitis is discussed.

An

    11-year-old
    AGE

    boy
    GENDER

 with

    Gaucher disease
    DIAGNOSIS

 developed

    acute bone pain of the left thigh
    SYMPTOMS

, accompanied by

    fever
    SYMPTOMS

 and

    signs of inflammation
    SYMPTOMS

. Initially

    he
    GENDER

 was treated as

    osteomyelitis
    DIAGNOSIS

    with antibiotics
    NEG_FINDINGS

.

    Cultures of blood and aspirate of a subperiosteal hematoma
    PARACLINICAL

 were

    negative for bacterial growth
    NEG_FINDINGS

.

    Tc99m bone scan
    PARACLINICAL

 revealed

    relatively decreased uptake over the involved area
    SYMPTOMS

, and the findings of

    magnetic resonance imaging
    PARACLINICAL

 were typical for

    Gaucher crisis
    DIAGNOSIS

. Although

    Ga 67 imaging was positive
    NEG_FINDINGS

, the diagnosis of a

    bone pain crisis
    DIAGNOSIS

 rather than an

    infection
    DIAGNOSIS

 was made.

    Antibiotics were discontinued without sequelae
    NEG_FINDINGS

.

    Differential diagnosis
    PARACLINICAL

 between

    Gaucher crisis
    DIAGNOSIS

 and

    osteomyelitis
    DIAGNOSIS

 is discussed.

Gaucher disease
osteomyelitis
Gaucher crisis
bone pain crisis
infection
Gaucher crisis
osteomyelitis


Mutation in the sphingolipid activator protein 2 in a patient with a variant of Gaucher disease.

The lysosomal degradation of glucosylceramide requires the hydrolase, glucosylceramide-beta-glucosidase and a sphingolipid activator protein (Gaucher factor, SAP-2, saposin C). Genetic defects in either of these lysosomal proteins cause phenotypically similar disorders in man, the Gaucher disease. SAP-2 originates from a gene which generates a mRNA that codes for four homologous proteins. In a patient with an immunologically proven SAP-2 deficiency a G1154----T transversion (counted from A of the initiation codon ATG) was found in the mRNA of the SAP-2 precursor which results in the substitution of Phe for Cys385 in the mature SAP-2. The rest of the coding sequence remained entirely normal.

The

    lysosomal degradation of glucosylceramide
    MICROSCOPIC

 requires the

    hydrolase, glucosylceramide-beta-glucosidase
    BIOCHEMICAL

 and a

    sphingolipid activator protein (Gaucher factor, SAP-2, saposin C)
    BIOCHEMICAL

.

    Genetic defects in
    GENETICS

 either of these

    lysosomal proteins
    BIOCHEMICAL

 cause phenotypically similar disorders in

    man
    GENDER

, the

    Gaucher disease
    DIAGNOSIS

.

    SAP-2
    BIOCHEMICAL

 originates from

    a gene which generates a mRNA that codes for four homologous proteins
    GENETICS

. In a patient with an

    immunologically proven SAP-2 deficiency
    NEG_FINDINGS

 a

    G1154----T transversion (counted from A of the initiation codon ATG) was found in the mRNA of the SAP-2 precursor which results in the substitution of Phe for Cys385 in the mature SAP-2
    GENETICS

. The

    rest of the coding sequence remained entirely normal
    NEG_FINDINGS

.


Molecular analysis of Gaucher disease in a Vietnamese-Czechoslovak patient with high residual glucocerebrosidase activity.

A Vietnamese-Czechoslovak type 1 Gaucher disease patient with mild hematological complications was found to have approximately 20% of the normal level of fibroblast glucocerebrosidase activity. Using primers that recognize exon 9 sequences of the glucocerebrosidase structural gene absent in the pseudogene, genomic DNA sequences flanking exons 9 and 10 of the glucocerebrosidase structural gene were amplified by the polymerase chain reaction. Allele-specific oligonucleotide hybridization to amplified genomic DNA sequence of exons 9 and 10 showed an A----G transition in exon 9 that resulted in the 370Ser----370Asp substitution in one of the alleles. In the other allele, a T----C transition in exon 10 resulted in the 444Leu----444Pro substitution, creating a NciI cleavage site. The heterozygote status of the patient's parents was confirmed biochemically by the detection of intermediate levels (42-55% of normal) of fibroblast glucocerebrosidase activity. Allele-specific oligonucleotide hybridization to amplified parental genomic DNA showed that the exon 9 mutation was present in the Czechoslovak father, whereas the exon 10 mutation was inherited from the patient's Vietnamese mother. This is the first report of the exon 10 mutation in a person of Vietnamese origin.

A

    Vietnamese-Czechoslovak
    ETHNICITY

    type 1 Gaucher disease
    DIAGNOSIS

 patient with

    mild hematological complications
    SYMPTOMS

 was found to have

    approximately 20% of the normal level of fibroblast glucocerebrosidase activity
    BIOCHEMICAL

. Using primers that recognize

    exon 9 sequences of the glucocerebrosidase structural gene absent in the pseudogene
    GENETICS

,

    genomic DNA sequences flanking exons 9 and 10 of the glucocerebrosidase structural gene
    PARACLINICAL

 were

    amplified by the polymerase chain reaction
    PARACLINICAL

.

    Allele-specific oligonucleotide hybridization to amplified genomic DNA sequence of exons 9 and 10
    PARACLINICAL

 showed an

    A----G transition in exon 9 that resulted in the 370Ser----370Asp substitution in one of the alleles
    GENETICS

.

    In the other allele, a T----C transition in exon 10 resulted in the 444Leu----444Pro substitution, creating a NciI cleavage site
    GENETICS

. The

    heterozygote status of the patient's parents
    FAMILY

 was confirmed biochemically by the

    detection of intermediate levels (42-55% of normal) of fibroblast glucocerebrosidase activity
    BIOCHEMICAL

.

    Allele-specific oligonucleotide hybridization to amplified parental genomic DNA
    PARACLINICAL

 showed that

    the exon 9 mutation was present in the Czechoslovak father
    FAMILY

, whereas

    the exon 10 mutation was inherited from the patient's Vietnamese mother
    FAMILY

. This is the first report of the

    exon 10 mutation
    GENETICS

 in a person of

    Vietnamese
    ETHNICITY

 origin.


Case report: serendipitous Gaucher's disease presenting as elevated erythrocyte sedimentation rate due to monoclonal gammopathy.

Immunoglobulin abnormalities have not been previously noted in totally asymptomatic patients with Gaucher's disease. We report a 40-year-old woman in whom Gaucher's disease was diagnosed during investigation for incidentally discovered elevated erythrocyte sedimentation rate. Further studies revealed IgG(lambda) monoclonal gammopathy. Physical examination and a bone survey disclosed none of the features of Gaucher's disease or multiple myeloma. We conclude that in contrast with previous observations, paraproteinemia may occur with Gaucher's disease even in the absence of splenomegaly or any one of the other features of the disease.

    Immunoglobulin abnormalities
    BIOCHEMICAL

 have not been previously noted in totally asymptomatic patients with

    Gaucher's disease
    DIAGNOSIS

. We report a

    40-year-old
    AGE

    woman
    GENDER

 in whom

    Gaucher's disease
    DIAGNOSIS

 was diagnosed during investigation for incidentally discovered

    elevated erythrocyte sedimentation rate
    BIOCHEMICAL

. Further studies revealed

    IgG(lambda) monoclonal gammopathy
    BIOCHEMICAL

.

    Physical examination
    PARACLINICAL

 and a

    bone survey
    PARACLINICAL

 disclosed

    none of the features of Gaucher's disease or multiple myeloma
    NEG_FINDINGS

. We conclude that in contrast with previous observations,

    paraproteinemia
    BIOCHEMICAL

 may occur with

    Gaucher's disease
    DIAGNOSIS

 even in the

    absence of splenomegaly or any one of the other features of the disease
    NEG_FINDINGS

.

Immunoglobulin abnormalities
elevated erythrocyte sedimentation rate
IgG(lambda) monoclonal gammopathy
paraproteinemia

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


Treatment of type 1 Gaucher's disease affecting bone with aminohydroxypropylidene bisphosphonate (pamidronate).

Two patients with Type 1 (adult) Gaucher's disease and major skeletal involvement with multiple fractures have been treated with the second generation bisphosphonate pamidronate for extensive periods. There was evidence of an immediate reduction in bone resorption, with increased calcium absorption (delayed in Patient 1), improved calcium balance and maintained or improved bone density indices in the axial and peripheral skeleton. There was no evidence of immediate relapse on treatment cessation. No toxic effects of pamidronate treatment were identified and subjective skeletal pain diminished in both patients. Histomorphometry of transiliac bone biopsies obtained before the start of treatment, after double in vivo tetracycline labelling, represents one of the earliest reports of the quantitative findings in iliac bone invaded by Gaucher cells.

Two patients with

    Type 1 (adult) Gaucher's disease
    DIAGNOSIS

 and

    major skeletal involvement
    SYMPTOMS

 with

    multiple fractures
    SYMPTOMS

 have been treated with the

    second generation bisphosphonate pamidronate for extensive periods
    MEDICATION

. There was evidence of an

    immediate reduction in bone resorption
    SYMPTOMS

, with

    increased calcium absorption
    BIOCHEMICAL

 (delayed in Patient 1),

    improved calcium balance
    BIOCHEMICAL

 and

    maintained or improved bone density indices in the axial and peripheral skeleton
    SYMPTOMS

. There was

    no evidence of immediate relapse
    NEG_FINDINGS

 on

    treatment cessation
    MEDICATION

.

    No toxic effects of pamidronate treatment
    NEG_FINDINGS

 were identified and

    subjective skeletal pain diminished
    SYMPTOMS

 in both patients.

    Histomorphometry of transiliac bone biopsies obtained before the
    PARACLINICAL

 start of treatment, after

    double in vivo tetracycline labelling
    PARACLINICAL

, represents one of the earliest reports of the

    quantitative findings in iliac bone invaded by Gaucher cells
    MICROSCOPIC

.

increased calcium absorption
improved calcium balance


[Gaucher's disease type I, anticoagulant factor and pregnancy].

In this paper, we show the presence of an anticoagulant factor which induced a prolongation of the partial time of thromboplastin (PTT) in a 23 year old female with Gaucher's disease and premature delivery. We discuss the importance of this factor and the therapeutic efficacy of the total splenectomy in this type of patient when spleen enlargement poses problems for the evolution of pregnancy to the end.

In this paper, we show the

    presence of an anticoagulant factor which induced a prolongation of the partial time of thromboplastin (PTT)
    BIOCHEMICAL

 in a

    23 year old
    AGE

    female
    GENDER

 with

    Gaucher's disease
    DIAGNOSIS

 and

    premature delivery
    SYMPTOMS

. We discuss the importance of this factor and the therapeutic efficacy of the

    total splenectomy
    MEDICATION

 in this type of patient when

    spleen enlargement
    SYMPTOMS

 poses problems for the

    evolution of pregnancy to the end
    SYMPTOMS

.

premature delivery
spleen enlargement
evolution of pregnancy to the end


The "Normandy" variant of von Willebrand disease: characterization of a point mutation in the von Willebrand factor gene.

We previously reported a functional defect of von Willebrand factor (vWF) in a new variant of von Willebrand disease (vWD) tentatively named vWD "Normandy." The present work has attempted to characterize the molecular abnormality of this vWF that fails to bind factor VIII (FVIII). The immunopurified vWF from normal and patient's plasma were digested by trypsin and the resulting peptides were compared. The electrophoresis of "vWF Normandy" showed a shift in the band corresponding to a polypeptide from amino acid 1 to 272. Consequently, we performed the molecular analysis of the portion of the vWF gene of this patient encoding this amino acid sequence. Exons 18-24 were amplified by the use of polymerase chain reaction and their nucleotide sequences corresponding to 1.8 kb were determined. Our analysis showed a point mutation C to T at codon 791, resulting in the substitution of Methionine for Threonine at position 28 of the mature vWF subunit. Because this nucleotide substitution destroyed a Mae II restriction site, this mutation was conveniently sought in various individual DNAs. The patterns obtained were consistent with the homozygous and heterozygous state of this mutation in the patient and in her son, respectively, and with its absence in 28 normal individuals. We conclude that Threonine at position 28 in plasma vWF may be crucial for the conformation and FVIII-binding capacity of its cystine-rich N-terminal domain.

We previously reported a

    functional defect of von Willebrand factor (vWF)
    BIOCHEMICAL

 in a new variant of

    von Willebrand disease (vWD)
    DIAGNOSIS

 tentatively named

    vWD "Normandy
    DIAGNOSIS

." The present work has attempted to characterize the molecular abnormality of this vWF that

    fails to bind factor VIII (FVIII)
    BIOCHEMICAL

. The

    immunopurified vWF
    BIOCHEMICAL

 from normal and patient's plasma were digested by trypsin and the resulting peptides were compared. The electrophoresis of "

    vWF Normandy
    BIOCHEMICAL

" showed a shift in the band corresponding to a

    polypeptide from amino acid 1 to 272
    BIOCHEMICAL

. Consequently, we performed the

    molecular analysis of the portion of the vWF gene
    PARACLINICAL

 of this patient encoding this

    amino acid sequence
    PARACLINICAL

.

    Exons 18-24 were amplified by the use of polymerase chain reaction
    PARACLINICAL

 and their

    nucleotide sequences corresponding to 1.8 kb were determined
    PARACLINICAL

. Our analysis showed a

    point mutation C to T at codon 791, resulting in the substitution of Methionine for Threonine at position 28 of the mature vWF subunit
    GENETICS

. Because this

    nucleotide substitution destroyed a Mae II restriction site
    GENETICS

, this mutation was conveniently sought in various individual DNAs. The patterns obtained were consistent with the

    homozygous and heterozygous state of this mutation in the patient and in her son
    FAMILY

, respectively, and with its absence in 28 normal individuals. We conclude that

    Threonine at position 28 in plasma vWF
    GENETICS

 may be crucial for the conformation and

    FVIII-binding
    BIOCHEMICAL

 capacity of its

    cystine-rich N-terminal domain
    BIOCHEMICAL

.

von Willebrand disease (vWD)
vWD "Normandy


Uncoupling of blood flow and oxygen metabolism in the cerebellum in type 3 Gaucher disease.

Cerebral blood flow and oxygen metabolism were measured in a fourteen-year-old girl with type 3 Gaucher disease by using positron emission tomography (PET). Cranial CT and MRI showed only mild brain atrophy. PET demonstrated uncoupling of cerebral blood flow and oxygen metabolism, that is, a mild increase of cerebral blood flow and a reduction of oxygen extraction fraction and cerebral metabolic rate of oxygen only in the cerebellum. Although the mechanism is unknown, the above finding may reflect the underlying pathogenesis of the disorder. PET seems to be more sensitive than CT and MRI in detecting some functional abnormalities in the affected structures. However, further investigations must be done before concluding that this finding is unique to type 3 Gaucher disease.

    Cerebral blood flow and oxygen metabolism were measured
    PARACLINICAL

 in a

    fourteen-year-old
    AGE

    girl
    GENDER

 with

    type 3 Gaucher disease
    DIAGNOSIS

 by using

    positron emission tomography (PET)
    PARACLINICAL

.

    Cranial CT
    PARACLINICAL

 and

    MRI
    PARACLINICAL

 showed

    only mild brain atrophy
    SYMPTOMS

.

    PET
    PARACLINICAL

 demonstrated

    uncoupling of cerebral blood flow and oxygen metabolism
    SYMPTOMS

, that is, a

    mild increase of cerebral blood flow
    SYMPTOMS

 and a

    reduction of oxygen extraction fraction and cerebral metabolic rate of oxygen only in the cerebellum
    BIOCHEMICAL

. Although the mechanism is unknown, the above finding may reflect the underlying pathogenesis of the disorder.

    PET
    PARACLINICAL

 seems to be more sensitive than

    CT
    PARACLINICAL

 and

    MRI
    PARACLINICAL

 in detecting some

    functional abnormalities in the affected structures
    SYMPTOMS

. However, further investigations must be done before concluding that this finding is unique to

    type 3 Gaucher disease
    DIAGNOSIS

.

type 3 Gaucher disease
type 3 Gaucher disease


Massive gastrointestinal haemorrhage associated with ileal lymphoid hyperplasia in Gaucher's disease.

A case report of adult type I Gaucher's disease is described, with profound terminal ileal haemorrhage in association with ileal lymphoid hyperplasia. Peroperative ileal endoscopy localized the segment involved allowing an appropriate resection and successful outcome for the patient.

A case report of

    adult
    AGE

    type I Gaucher's disease
    DIAGNOSIS

 is described, with

    profound terminal ileal haemorrhage
    SYMPTOMS

 in association with

    ileal lymphoid hyperplasia
    SYMPTOMS

.

    Peroperative ileal endoscopy
    PARACLINICAL

 localized the segment involved allowing an

    appropriate resection
    MEDICATION

 and successful outcome for the patient.

profound terminal ileal haemorrhage
ileal lymphoid hyperplasia


[Coincidence of Gaucher disease with primary hepatocellular carcinoma].

Case report on a 48-year-old man with Gaucher's disease and a HBsAg-positive cirrhosis simultaneously. Postmortem examination revealed a hepatocellular carcinoma suggested by antecedent ultrasound examination. The coexistence of Gaucher's disease and hepatocellular carcinoma has not been described before. A possible relationship between Gaucher's disease and hepatocellular carcinoma is supposed due to Gaucher's disease and association to the hepatitis B infection.

Case report on a

    48-year-old
    AGE

    man
    GENDER

 with

    Gaucher's disease
    DIAGNOSIS

 and a

    HBsAg-positive cirrhosis
    DIAGNOSIS

 simultaneously.

    Postmortem examination
    PARACLINICAL

 revealed a

    hepatocellular carcinoma
    DIAGNOSIS

 suggested by

    antecedent ultrasound examination
    PARACLINICAL

. The

    coexistence of Gaucher's disease
    DIAGNOSIS

 and

    hepatocellular carcinoma
    DIAGNOSIS

 has not been described before. A possible

    relationship between Gaucher's disease
    DIAGNOSIS

 and

    hepatocellular carcinoma
    DIAGNOSIS

 is supposed due to

    Gaucher's disease
    DIAGNOSIS

 and

    association to the hepatitis B infection
    DIAGNOSIS

.


[Gaucher's disease].

Two cases of Gaucher's disease are described. The diagnosis was based on clinical appearance, observation of the typical cells in the sternal and splenic puncture biopsies. Leucocytic beta-glucocerebrosidase activity was found inhibited in contrast to normal activity of the other lysosomal glycosidases. A female of 51 developed significant changes in the bones, progressive enlargement of the liver, chronic calculous cholecystitis 36 years after splenectomy. Current aspects of pathogenesis, clinical symptoms, diagnosis and treatment of Gaucher's disease are reviewed.

Two cases of

    Gaucher's disease
    DIAGNOSIS

 are described. The diagnosis was based on clinical appearance,

    observation of the typical cells in the sternal and splenic puncture biopsies
    MICROSCOPIC

.

    Leucocytic beta-glucocerebrosidase activity was found inhibited
    BIOCHEMICAL

 in contrast to

    normal activity of the other lysosomal glycosidases
    NEG_FINDINGS

. A

    female
    GENDER

 of

    51
    AGE

 developed

    significant changes in the bones
    SYMPTOMS

,

    progressive enlargement of the liver
    SYMPTOMS

,

    chronic calculous cholecystitis
    DIAGNOSIS

 36 years after

    splenectomy
    MEDICATION

. Current aspects of pathogenesis, clinical symptoms, diagnosis and treatment of

    Gaucher's disease
    DIAGNOSIS

 are reviewed.

Gaucher's disease
chronic calculous cholecystitis
Gaucher's disease

significant changes in the bones
progressive enlargement of the liver


Gaucher's disease complicated by bleeding esophageal varices and colonic infiltration by Gaucher cells.

We report a 10-yr-old child with Gaucher's disease who developed upper gastrointestinal bleeding from esophageal varices, as well as hemorrhage from a colonic polyp infiltrated with Gaucher cells. Both the varices and polyp were treated endoscopically, and the outcome was successful. Although gastrointestinal hemorrhage due to portal hypertension is considered a rare complication of Gaucher's disease, colonic infiltration with Gaucher cells has not been recognized previously.

We report a

    10-yr-old
    AGE

    child
    AGE

 with

    Gaucher's disease
    DIAGNOSIS

 who developed

    upper gastrointestinal bleeding from esophageal varices
    SYMPTOMS

, as well as

    hemorrhage from a colonic polyp infiltrated with Gaucher cells
    SYMPTOMS

. Both the

    varices and polyp
    SYMPTOMS

 were

    treated endoscopically
    MEDICATION

, and the outcome was successful. Although

    gastrointestinal hemorrhage due to portal hypertension
    SYMPTOMS

 is considered a rare complication of

    Gaucher's disease
    DIAGNOSIS

,

    colonic infiltration with Gaucher cells
    MICROSCOPIC

 has not been recognized previously.


[Difficulties in the diagnosis of Gaucher's disease].

The first diagnostic phase of Gaucher's disease is based on correct evaluation of clinical history as well as on finding of typical striated Gaucher's cells in bone marrow. Nevertheless, there can occur surprising diagnostic faults in spite of believed easy identification of this classic storage disease. They can be caused by a primary atypical or secondary modified clinical phenotype. Another source of diagnostic error or hesitation can be in an atypical appearance of Gaucher's cells because of poorly distinct cytoplasmic striation (solid voluminous cytoplasm) or classical vacuolized pattern.

The first diagnostic phase of

    Gaucher's disease
    DIAGNOSIS

 is based on correct evaluation of clinical history as well as on finding of

    typical striated Gaucher's cells in bone marrow
    MICROSCOPIC

. Nevertheless, there can occur surprising diagnostic faults in spite of believed easy identification of this classic

    storage disease
    DIAGNOSIS

. They can be caused by a primary atypical or secondary modified clinical phenotype. Another source of diagnostic error or hesitation can be in an

    atypical appearance of Gaucher's cells
    MICROSCOPIC

 because of

    poorly distinct cytoplasmic striation (solid voluminous cytoplasm)
    MICROSCOPIC

 or

    classical vacuolized pattern
    MICROSCOPIC

.


A case of nonneurologic Gaucher's disease that biochemically resembles the neurologic types.

Systemic findings such as hepatosplenomegaly and typical Gaucher storage cells in a bone marrow aspirate led to the clinical diagnosis of Gaucher's disease in the seven-year old patient described in this report. On the basis of the lack of neurologic involvement the child was classified as having the Type 1, nonneurologic form of Gaucher's disease. After splenectomy glucocerebrosidase was extracted from her spleen for biochemical analysis. As expected, a marked deficiency of glucocerebrosidase activity was evident in the splenic extract, however her enzyme displayed anomalous behavior compared to other identical splenic preparations from documented Type 1 Gaucher's disease patients in that it failed to reconstitute with the acidic lipid phosphatidylserine. Using the polymerase chain reaction (PCR)-based color complementation assay and restriction endonuclease analysis, we compared the mutation genotype of this child with that of five other classical Type 1 patients. This analysis revealed that our patient alone was homoallelic for a T----C transition at position 1448 in the glucocerebrosidase cDNA that results in a 444Leu----Pro substitution in the glucocerebrosidase protein. The latter mutation genotype is normally associated with the neurologic phenotype, namely, the Types 2 and 3 forms of the disease. The relevance of the nature of polarity in clinical and biochemical analyses is discussed with regard to the phenotypic classification and the future clinical course of disease in the child.

    Systemic findings
    SYMPTOMS

 such as

    hepatosplenomegaly
    SYMPTOMS

 and

    typical Gaucher storage cells in a bone marrow aspirate
    MICROSCOPIC

 led to the clinical diagnosis of

    Gaucher's disease
    DIAGNOSIS

 in the

    seven-year old
    AGE

 patient described in this report. On the basis of the

    lack of neurologic involvement
    NEG_FINDINGS

 the

    child
    AGE

 was classified as having the

    Type 1, nonneurologic form of Gaucher's disease
    DIAGNOSIS

. After

    splenectomy
    MEDICATION

    glucocerebrosidase was extracted from her spleen for biochemical analysis
    PARACLINICAL

. As expected, a

    marked deficiency of glucocerebrosidase activity was evident in the splenic extract
    BIOCHEMICAL

, however

    her
    GENDER

 enzyme displayed

    anomalous behavior compared
    BIOCHEMICAL

 to other identical splenic preparations from documented

    Type 1 Gaucher's disease
    MICROSCOPIC

 patients in that it

    failed to reconstitute with the acidic lipid phosphatidylserine
    BIOCHEMICAL

. Using the

    polymerase chain reaction (PCR)-based color complementation assay
    PARACLINICAL

 and

    restriction endonuclease analysis
    PARACLINICAL

, we compared the mutation genotype of this

    child
    AGE

 with that of five other classical

    Type 1
    DIAGNOSIS

 patients. This analysis revealed that our patient alone was

    homoallelic for a T----C transition at position 1448 in the glucocerebrosidase cDNA that results in a 444Leu----Pro substitution in the glucocerebrosidase protein
    GENETICS

. The

    latter mutation genotype
    GENETICS

 is normally associated with the

    neurologic
    DIAGNOSIS

 phenotype, namely, the

    Types 2 and 3 forms of the disease
    DIAGNOSIS

. The relevance of the nature of polarity in clinical and biochemical analyses is discussed with regard to the phenotypic classification and the future clinical course of disease in the

    child
    AGE

.


Gaucher's disease affecting the mandible and maxilla. Report of a case.

Gaucher's disease is a rare autosomal, recessive disorder characterized by deficiency of lyzosomal hydrolase glucocerebrosidase, and showing predilection for Ashkenazi Jews. A case of Gaucher's disease affecting both jaws and initially diagnosed by mandibular biopsy is described.

    Gaucher's disease
    DIAGNOSIS

 is a

    rare autosomal, recessive disorder
    GENETICS

 characterized by

    deficiency of lyzosomal hydrolase glucocerebrosidase
    BIOCHEMICAL

, and showing predilection for

    Ashkenazi Jews
    ETHNICITY

. A case of

    Gaucher's disease
    DIAGNOSIS

    affecting both jaws
    SYMPTOMS

 and initially diagnosed by

    mandibular biopsy
    PARACLINICAL

 is described.


[Correction of fatal genetic diseases using bone marrow transplantation. 2].

Genetic diseases can be treated by transplantation of normal allogeneic bone marrow. Four patients with congenital disorders of their hematopoietic and/or lymphoid stem cells have been transplanted. One patient had a congenital aplastic anemia (Blackfan-Diamond), one had Gaucher's disease, one had congenital agranulocytosis Kostmann and one had chronic granulomatous disease. All patients received busulfan, cyclophosphamide and total nodal irradiation as preparatory regimen. Total nodal irradiation and cyclophosphamide were used as immunosuppressive agents. In all cases hematopoietic ablation and donor lymphoid and hematopoietic engraftment were achieved. The basic disorders of all transplanted children could be corrected completely. All children are alive and well.

    Genetic diseases
    DIAGNOSIS

 can be treated by

    transplantation of normal allogeneic bone marrow
    MEDICATION

. Four patients with

    congenital disorders of their hematopoietic and/or lymphoid stem cells
    DIAGNOSIS

 have been

    transplanted
    MEDICATION

. One patient had a

    congenital aplastic anemia (Blackfan-Diamond)
    DIAGNOSIS

, one had

    Gaucher's disease
    DIAGNOSIS

, one had

    congenital agranulocytosis Kostmann
    DIAGNOSIS

 and one had

    chronic granulomatous disease
    DIAGNOSIS

. All patients received

    busulfan, cyclophosphamide and total nodal irradiation as preparatory regimen
    MEDICATION

.

    Total nodal irradiation and cyclophosphamide
    MEDICATION

 were used as

    immunosuppressive agents
    MEDICATION

. In all cases

    hematopoietic ablation
    MEDICATION

 and

    donor lymphoid and hematopoietic engraftment
    MICROSCOPIC

 were achieved. The basic disorders of all transplanted children could be corrected completely. All

    children
    AGE

 are alive and well.


[Gaucher's disease and pregnancy].

Gaucher's disease is rare in association with pregnancy (we have only found 53 cases of women with this disease who had at least one pregnancy since 1945). A review of literature on this subject and this one case confirms that it is unlikely that the disease will progress as far as the symptomatology is concerned and that there are unlikely to be obstetric or fetal complications. All the same there are certain complications that can occur as the haematological state is concerned (thrombocytopenia, coagulation defects such as bleeding, particularly post-partum from the genital organs). Mechanical difficulties may occur because of the greatly enlarged spleen. Pregnancy is not contra-indicated but it is a high risk pregnancy that has to watched very carefully with ultrasound and great attention to the obstetric and biological condition.

    Gaucher's disease
    DIAGNOSIS

 is rare in association with

    pregnancy
    DIAGNOSIS

 (we have only found 53 cases of

    women
    GENDER

 with this disease who had at least one

    pregnancy
    DIAGNOSIS

 since 1945). A review of literature on this subject and this one case confirms that it is unlikely that the disease will progress as far as the symptomatology is concerned and that there are unlikely to be

    obstetric or fetal complications
    NEG_FINDINGS

. All the same there are certain complications that can occur as the haematological state is concerned (

    thrombocytopenia
    BIOCHEMICAL

,

    coagulation defects such as bleeding, particularly post-partum from the genital organs
    SYMPTOMS

).

    Mechanical difficulties
    SYMPTOMS

 may occur because of the

    greatly enlarged spleen
    SYMPTOMS

.

    Pregnancy
    DIAGNOSIS

 is

    not contra-indicated
    NEG_FINDINGS

 but it is a high risk pregnancy that has to watched very carefully with

    ultrasound
    PARACLINICAL

 and great attention to the obstetric and biological condition.

Gaucher's disease
pregnancy
pregnancy
Pregnancy

obstetric or fetal complications
not contra-indicated


Norrbottnian type of Gaucher disease--clinical, biochemical and molecular biology aspects: successful treatment with bone marrow transplantation.

The Norrbottnian type of Gaucher disease is a well defined nosological entity with a characteristic course and clinical manifestations. The disease is caused by a deficiency of the enzyme glucosylceramidase (cerebroside-beta-glucosidase). Studies of genomic DNA and cDNA encoding the enzyme show a single base substitution in exon 10 in the Norrbottnian patients. The enzymic lesion causes an accumulation of glucosylceramide and glucosylsphingosine in cells of the monocyte-macrophage system, particularly in spleen, liver and bone marrow. Early splenectomy results in severe symptoms from skeleton and CNS, owing to accelerated storage of glucosylceramide in these organs. Bone marrow transplantation had a life-saving effect and seems to be the method of choice for beneficial enzyme replacement therapy.

The

    Norrbottnian type of Gaucher disease
    DIAGNOSIS

 is a well defined nosological entity with a characteristic course and clinical manifestations. The disease is caused by a

    deficiency of the enzyme glucosylceramidase (cerebroside-beta-glucosidase)
    BIOCHEMICAL

.

    Studies of genomic DNA and cDNA encoding the enzyme
    PARACLINICAL

 show a

    single base substitution in exon 10
    GENETICS

 in the

    Norrbottnian
    ETHNICITY

 patients. The

    enzymic lesion
    MICROSCOPIC

 causes an

    accumulation of glucosylceramide and glucosylsphingosine in cells of the monocyte-macrophage system, particularly in spleen, liver and bone marrow
    MICROSCOPIC

.

    Early splenectomy
    MEDICATION

 results in

    severe symptoms from skeleton and CNS
    SYMPTOMS

, owing to

    accelerated storage of glucosylceramide in these organs
    MICROSCOPIC

.

    Bone marrow transplantation
    MEDICATION

 had a life-saving effect and seems to be the method of choice for

    beneficial enzyme replacement therapy
    MEDICATION

.

Early splenectomy
Bone marrow transplantation
beneficial enzyme replacement therapy


Late-infantile Gaucher disease in a child with myoclonus and bulbar signs: neuropathological and neurochemical findings.

Clinical, neurochemical and neuropathological findings on a case of late-infantile Gaucher disease with oculomotor apraxia, progressive myoclonus and prominent bulbar signs are reported. There was a marked increase in glucosylceramide in cerebral cortex and cerebellum; the increase was more in the range of that seen in the Norrbottnian type III than in type II Gaucher disease. Cerebral cortical changes were characterized by a band-like intraparenchymal accumulation of Gaucher cells in lamina IV with an accompanying astrogliosis. In the cerebellum, a focal severe loss of granule cells and a global loss of dentate nucleus neurons was recorded. Milder changes were seen in thalamus and brain stem where perivascular accumulation of Gaucher cells was present in all regions. The cerebral cortical changes resembled those seen in type II Gaucher disease and was much more marked than in the Norrbottnian type III, whereas the changes in the dentate nucleus were more severe than in both type II and type III. The phenotypic variability with different patterns of clinical symptoms and neuropathological changes in neuronopathic Gaucher disease is discussed.

Clinical, neurochemical and neuropathological findings on a case of

    late-infantile
    AGE

    Gaucher disease
    DIAGNOSIS

 with

    oculomotor apraxia
    SYMPTOMS

,

    progressive myoclonus
    SYMPTOMS

 and

    prominent bulbar signs
    SYMPTOMS

 are reported. There was a

    marked increase in glucosylceramide in cerebral cortex and cerebellum
    MICROSCOPIC

; the increase was more in the range of that seen in the Norrbottnian type III than in

    type II Gaucher disease
    DIAGNOSIS

.

    Cerebral cortical changes
    SYMPTOMS

 were characterized by a

    band-like intraparenchymal accumulation of Gaucher cells in lamina IV
    MICROSCOPIC

 with an accompanying

    astrogliosis
    MICROSCOPIC

. In the

    cerebellum
    SYMPTOMS

, a

    focal severe loss of granule cells
    SYMPTOMS

 and a

    global loss of dentate nucleus neurons
    MICROSCOPIC

 was recorded.

    Milder changes were seen in thalamus and brain stem
    SYMPTOMS

 where

    perivascular accumulation of Gaucher cells was present in all regions
    MICROSCOPIC

. The

    cerebral cortical changes
    SYMPTOMS

 resembled those seen in

    type II Gaucher disease
    DIAGNOSIS

 and was much more marked than in the

    Norrbottnian type III
    DIAGNOSIS

, whereas the

    changes in the dentate nucleus were more severe
    SYMPTOMS

 than in both

    type II and type III
    DIAGNOSIS

. The phenotypic variability with different patterns of clinical symptoms and

    neuropathological changes
    SYMPTOMS

 in

    neuronopathic Gaucher disease
    DIAGNOSIS

 is discussed.

Gaucher disease
type II Gaucher disease
type II Gaucher disease
Norrbottnian type III
type II and type III
neuronopathic Gaucher disease


Light microscopic and ultrastructural study on CNS lesions in infantile Gaucher's disease.

We report on the light microscopic and ultrastructural CNS findings and the clinical course in a boy with infantile Gaucher's disease who died at 6 1/2 months. Besides the morphological alterations described in the literature, like perivascular Gaucher cells and nerve cell loss, our case was characterized by an unusually extensive proliferation of GFAP-positive astrocytes in the vicinity of stored material but also in regions where no storage was detected. Electron microscopy revealed massively enlarged lysosomes in the storage cells. The lysosomes showed twisted tubular structures, some of them penetrating the outer membrane. Isolated tubules were found to lie free in the cytosol. These tubules correspond to stored crystallized glucocerebroside molecules, which are most stable in this twisted arrangement.

We report on the

    light microscopic and ultrastructural CNS
    PARACLINICAL

 findings and the clinical course in a

    boy
    GENDER

 with

    infantile Gaucher's disease
    DIAGNOSIS

 who

    died
    SYMPTOMS

    at 6 1/2 months
    AGE

. Besides the

    morphological alterations
    SYMPTOMS

 described in the literature, like

    perivascular Gaucher cells
    MICROSCOPIC

 and

    nerve cell loss
    MICROSCOPIC

, our case was characterized by an

    unusually extensive proliferation of GFAP-positive astrocytes in the vicinity of stored material but also in regions
    MICROSCOPIC

 where

    no storage was detected
    NEG_FINDINGS

.

    Electron microscopy
    PARACLINICAL

 revealed

    massively enlarged lysosomes in the storage cells
    MICROSCOPIC

.

    The lysosomes showed twisted tubular structures, some of them penetrating the outer membrane
    MICROSCOPIC

.

    Isolated tubules were found to lie free in the cytosol
    MICROSCOPIC

.

    These tubules correspond to stored crystallized glucocerebroside molecules, which are most stable in this twisted arrangement
    MICROSCOPIC

.


Annulo-aortic ectasia with DeBakey type II dissecting aneurysm in Gaucher's disease.

Annulo-aortic ectasia is an extremely rare complication of Gaucher's disease. We report successful surgery in a patient with Gaucher's disease complicated by annulo-aortic ectasia and aortic dissection. Cabrol's operation was accomplished without bleeding or sternal adaptation problems.

    Annulo-aortic ectasia
    SYMPTOMS

 is an extremely rare complication of

    Gaucher's disease
    DIAGNOSIS

. We report

    successful surgery
    MEDICATION

 in a patient with

    Gaucher's disease
    DIAGNOSIS

 complicated by

    annulo-aortic ectasia
    SYMPTOMS

 and

    aortic dissection
    SYMPTOMS

.

    Cabrol's operation
    MEDICATION

 was accomplished

    without bleeding or sternal adaptation problems
    NEG_FINDINGS

.

Annulo-aortic ectasia
annulo-aortic ectasia
aortic dissection


Gaucher's disease type I. Report of a case with prominent deposition of ceroid in splenic endothelial cells and intestinal smooth muscle fibers.

A case of type I Gaucher's disease in a 39-year-old male is reported. Autopsy showed marked enlargement of the spleen (3,070 g) and infiltration of typical Gaucher's cells in the spleen, liver, bone, marrow, gastrointestinal tract, lymph nodes and adrenal glands. The diagnosis of Gaucher's disease was ascertained by the very low beta-glucosidase activity of cultured subcutaneous fibroblasts and the high content of glucocerebroside in the spleen tissue. A peculiar finding in this case was prominent deposition of brown pigment in endothelial cells of the spleen and smooth muscles fibers of the gastrointestinal tract, urinary bladder and prostate. Histochemical examination revealed that the granules in endothelial cells and smooth muscle fibers were ceroid. Such deposition of ceroid has never been reported previously in Gaucher's disease. Ceroid deposition in generalized smooth muscle fibers is known as brown bowel syndrome, and is highly suggestive of severe vitamin E deficiency. Although other symptoms of vitamin E deficiency were not noticed in this case, some malnutritional condition might play a role in prominent deposition of ceroid in lysosomes, possibly together with deficient activity of a lysosomal enzyme.

A case of

    type I Gaucher's disease
    DIAGNOSIS

 in a

    39-year-old
    AGE

    male
    GENDER

 is reported.

    Autopsy
    PARACLINICAL

 showed

    marked enlargement of the spleen (3,070 g)
    SYMPTOMS

 and

    infiltration of typical Gaucher's cells in the spleen, liver, bone, marrow, gastrointestinal tract, lymph nodes and adrenal glands
    MICROSCOPIC

. The diagnosis of

    Gaucher's disease
    DIAGNOSIS

 was ascertained by the

    very low beta-glucosidase activity of cultured subcutaneous fibroblasts
    BIOCHEMICAL

 and the

    high content of glucocerebroside in the spleen tissue
    MICROSCOPIC

. A peculiar finding in this case was

    prominent deposition of brown pigment in endothelial cells of the spleen and smooth muscles fibers of the gastrointestinal tract, urinary bladder and prostate
    MICROSCOPIC

.

    Histochemical examination
    PARACLINICAL

 revealed that

    the granules in endothelial cells and smooth muscle fibers were ceroid
    MICROSCOPIC

. Such

    deposition of ceroid
    MICROSCOPIC

 has never been reported previously in

    Gaucher's disease
    DIAGNOSIS

.

    Ceroid deposition in generalized smooth muscle fibers
    MICROSCOPIC

 is known as

    brown bowel syndrome
    DIAGNOSIS

, and is highly suggestive of

    severe vitamin E deficiency
    BIOCHEMICAL

. Although

    other symptoms of vitamin E deficiency were not noticed
    NEG_FINDINGS

 in this case, some malnutritional condition might play a role in

    prominent deposition of ceroid in lysosomes
    MICROSCOPIC

, possibly together with

    deficient activity of a lysosomal enzyme
    BIOCHEMICAL

.

type I Gaucher's disease
Gaucher's disease
Gaucher's disease
brown bowel syndrome


[Gaucher disease and pregnancy].

Up to date, initial or recurrent pregnancy has been reported in 46 patients suffering from Gaucher's disease. In the present review of the literature, potential complications and therapeutic concepts are outlined and a case report of a 22-year-old primipara is presented.

Up to date,

    initial or recurrent pregnancy
    SYMPTOMS

 has been reported in 46 patients suffering from

    Gaucher's disease
    DIAGNOSIS

. In the present review of the literature, potential complications and therapeutic concepts are outlined and a case report of a

    22-year-old
    AGE

    primipara
    GENDER

 is presented.


Gaucher disease associated with a unique KpnI restriction site: identification of the amino-acid substitution.

In an earlier survey of the glucocerebrosidase locus using 20 restriction enzymes and a 1039 bp probe we found that 1 of 9 Gaucher disease patients had a unique pattern with KpnI. a pattern that was not observed in any other Gaucher patient or in 31 controls. We have now localized the mutation in this patient to a T----A transversion in nucleotide 764 of the cDNA occurring on one of the two glucocerebrosidase alleles. The presumed abnormality in the other allele has not been identified. The deduced amino-acid change in the allele with the mutation at nucleotide 764 is a relatively drastic alteration of amino acid 255 from phenylalanine to tyrosine. The genomic DNAs of 31 other Gaucher disease patients (representing 62 Gaucher disease alleles) were examined for this mutation using the polymerase chain reaction. None were found to have this abnormality.

In an earlier survey of the

    glucocerebrosidase locus
    PARACLINICAL

 using 20 restriction enzymes and a 1039 bp probe we found that 1 of 9

    Gaucher disease
    DIAGNOSIS

 patients had a unique pattern with KpnI. a pattern that was not observed in any other

    Gaucher
    DIAGNOSIS

 patient or in 31 controls. We have now localized the mutation in this patient

    to a T----A transversion in nucleotide 764 of the cDNA occurring on one of the two glucocerebrosidase alleles
    GENETICS

. The

    presumed abnormality in the other allele has not been identified
    GENETICS

. The

    deduced amino-acid change in the allele with the mutation at nucleotide 764 is a relatively drastic alteration of amino acid 255 from phenylalanine to tyrosine
    GENETICS

. The

    genomic DNAs
    PARACLINICAL

 of 31 other

    Gaucher disease
    DIAGNOSIS

 patients (representing 62

    Gaucher disease
    DIAGNOSIS

 alleles) were examined for this mutation

    using the polymerase chain reaction
    PARACLINICAL

. None were found to have this abnormality.

Gaucher disease
Gaucher
Gaucher disease
Gaucher disease


Rapidly progressive type III Gaucher disease: deterioration following partial splenectomy.

Total splenectomy has been found to accelerate disease progression in Type III Gaucher disease, therefore partial splenic resection was performed in a 28 month old girl with rapidly progressive (non-Norrbottnian) Type III disease to alleviate the effects of hypersplenism. Surgery failed to arrest the disease process and splenomegaly recurred within three months. The erythrocyte glucosylceramide level increased post-operatively. Post-mortem studies revealed dense accumulation of Gaucher cells in spleen, liver, lungs, bone marrow and within the central nervous system. The glucosylceramide content of brain and liver was elevated to the range previously noted in splenectomised Norrbottnian patients. Thus, in rapidly progressive Type III Gaucher disease, neither total nor partial splenectomy alone provides a favourable outcome.

    Total splenectomy
    MEDICATION

 has been found to accelerate disease progression in

    Type III Gaucher disease
    DIAGNOSIS

, therefore

    partial splenic resection
    MEDICATION

 was performed in a

    28 month old
    AGE

    girl
    GENDER

 with

    rapidly progressive (non-Norrbottnian) Type III disease
    DIAGNOSIS

 to alleviate the effects of

    hypersplenism
    BIOCHEMICAL

.

    Surgery failed to arrest the disease process
    NEG_FINDINGS

 and

    splenomegaly recurred
    SYMPTOMS

 within three months. The

    erythrocyte glucosylceramide level increased
    BIOCHEMICAL

 post

    -operatively
    BIOCHEMICAL

.

    Post-mortem studies
    PARACLINICAL

 revealed

    dense accumulation of Gaucher cells in spleen, liver, lungs, bone marrow and within the central nervous system
    MICROSCOPIC

.

    The glucosylceramide content of brain and liver was elevated to the range previously noted
    MICROSCOPIC

 in

    splenectomised Norrbottnian
    NEG_FINDINGS

 patients. Thus, in

    rapidly progressive Type III Gaucher disease
    DIAGNOSIS

, neither

    total nor partial splenectomy
    MEDICATION

 alone provides a favourable outcome.

Total splenectomy
partial splenic resection
total nor partial splenectomy


Skeletal complications of type I Gaucher disease: the magnetic resonance features.

Abnormalities on magnetic resonance imaging (MRI) are reported in six individuals with various skeletal complications of type I Gaucher disease. The changes were a nonhomogeneous reduction in both T1 and T2 marrow signals with increased T2 signals during avascular episodes. MRI proved an excellent technique for the assessment of bone marrow changes in Type I Gaucher disease and for assessing avascular complications. It was not able to differentiate between pseudo-osteomyelitis and pyogenic osteomyelitis without clinical correlation. The problems studied included the extent of intramedullary Gaucher cell infiltration, avascular necrosis of femoral heads, assessment of bone pain from pseudo-osteomyelitis and the relationship of skeletal disease to splenectomy.

Abnormalities on

    magnetic resonance imaging (MRI)
    PARACLINICAL

 are reported in six individuals with various

    skeletal complications
    SYMPTOMS

 of

    type I Gaucher disease
    DIAGNOSIS

. The changes were a

    nonhomogeneous reduction in both T1 and T2 marrow signals with increased T2 signals during avascular episodes
    SYMPTOMS

.

    MRI
    PARACLINICAL

 proved an excellent technique for the assessment of

    bone marrow changes
    SYMPTOMS

 in

    Type I Gaucher disease
    DIAGNOSIS

 and for assessing

    avascular complications
    SYMPTOMS

. It was not able to differentiate between

    pseudo-osteomyelitis
    DIAGNOSIS

 and

    pyogenic osteomyelitis
    NEG_FINDINGS

 without clinical correlation. The problems studied included the extent of

    intramedullary Gaucher cell infiltration
    MICROSCOPIC

,

    avascular necrosis of femoral heads
    SYMPTOMS

, assessment of

    bone pain
    SYMPTOMS

 from

    pseudo-osteomyelitis
    SYMPTOMS

 and the relationship of

    skeletal disease
    DIAGNOSIS

 to

    splenectomy
    MEDICATION

.

type I Gaucher disease
Type I Gaucher disease
pseudo-osteomyelitis
skeletal disease


Therapeutic response to intravenous infusions of glucocerebrosidase in a patient with Gaucher disease.

Enzyme replacement has been under consideration as a therapeutic strategy for patients with Gaucher disease for more than two decades. Previous studies indicated that single injections of purified glucocerebrosidase reduced the amount of storage material in the liver. It was important to determine whether administration of exogenous enzyme on a regular basis would be of clinical benefit. We report here that weekly i.v. infusions of a macrophage-targeted preparation of human placental glucocerebrosidase in a child with type 1 Gaucher disease increased hemoglobin from 6.9 +/- 0.8 g/dl (+/- 1 SD) to 10.2 +/- 0.4 g/dl (+/- 1 SD) over a 20-week period. The platelet count also increased from a pretreatment value of 30,000 +/- 7000/mm3 (+/- 1 SD) to 54,000 +/- 11,000/mm3 (+/- 1 SD). Phagocytic activity in the spleen decreased during the period of enzyme administration, and there was radiographic evidence of skeletal improvement. These observations document objective clinical responses to enzyme supplementation in a patient with a sphingolipid storage disorder.

    Enzyme replacement
    MEDICATION

 has been under consideration as a therapeutic strategy for patients with

    Gaucher disease
    DIAGNOSIS

 for more than two decades. Previous studies indicated that

    single injections of purified glucocerebrosidase reduced the amount of storage material in the liver
    MEDICATION

. It was important to determine whether

    administration of exogenous enzyme
    MEDICATION

 on a regular basis would be of clinical benefit. We report here that

    weekly i.v. infusions of a macrophage-targeted preparation of human placental glucocerebrosidase
    MEDICATION

 in a

    child
    AGE

 with

    type 1 Gaucher disease
    DIAGNOSIS

    increased hemoglobin from 6.9 +/- 0.8 g/dl (+/- 1 SD) to 10.2 +/- 0.4 g/dl (+/- 1 SD)
    BIOCHEMICAL

    over a 20-week period
    MEDICATION

.

    The platelet count also increased from a pretreatment value of 30,000 +/- 7000/mm3 (+/- 1 SD) to 54,000 +/- 11,000/mm3 (+/- 1 SD)
    BIOCHEMICAL

.

    Phagocytic activity in the spleen decreased
    MICROSCOPIC

 during the

    period of enzyme administration
    MEDICATION

, and there was

    radiographic evidence of skeletal improvement
    SYMPTOMS

. These observations document objective clinical responses to

    enzyme supplementation
    MEDICATION

 in a patient with a

    sphingolipid storage disorder
    DIAGNOSIS

.

Gaucher disease
type 1 Gaucher disease
sphingolipid storage disorder


Ninety-five percent splenectomy for massive splenomegaly: a new surgical approach.

Subtotal splenectomy for children with Gaucher's disease has been a major contribution. When spleens of massive size are mobilized for partial resection, it may be technically difficult to remove more than 80% to 85% and still maintain hilar blood supply. The short gastric vessels are enlarged in patients who have marked splenomegaly and provide sufficient vascularity to support the 5% of remaining spleen that is desired in these patients. When the upper pole of the spleen is retained, as in the present case, the cut surface is relatively small and hemostasis is technically easier to achieve than when resection is performed closer to the center of the spleen.

    Subtotal splenectomy
    MEDICATION

 for

    children
    AGE

 with

    Gaucher's disease
    DIAGNOSIS

 has been a major contribution. When

    spleens of massive size
    SYMPTOMS

 are

    mobilized for partial resection
    MEDICATION

, it may be technically difficult to

    remove more than 80% to 85%
    MEDICATION

 and

    still maintain hilar blood supply
    NEG_FINDINGS

. The

    short gastric vessels are enlarged
    SYMPTOMS

 in patients who have

    marked splenomegaly
    SYMPTOMS

 and provide sufficient vascularity to

    support the 5% of remaining spleen
    MEDICATION

 that is desired in these patients. When

    the upper pole of the spleen is retained
    MEDICATION

, as in the present case, the cut surface is relatively small and

    hemostasis
    MEDICATION

 is technically easier to achieve than when

    resection is performed closer to the center of the spleen
    MEDICATION

.

spleens of massive size
short gastric vessels are enlarged
marked splenomegaly


Autoimmune hemolytic anemia in Gaucher's disease.

A 23-year-old Ashkenazi woman with Gaucher's disease developed Coombs-positive warm-type autoimmune hemolytic anemia. Treatment with high-dose steroids resulted in complete remission within 2 weeks. Study of an additional 72 patients with Gaucher's disease revealed another case of Coombs-positive warm-type autoimmune hemolytic anemia; other autoimmune disorders were found in 17 of these patients. The possible association of Coombs-positive hemolytic anemia and Gaucher's disease is discussed.

A

    23-year-old
    AGE

    Ashkenazi
    ETHNICITY

    woman
    GENDER

 with

    Gaucher's disease
    DIAGNOSIS

 developed

    Coombs-positive warm-type autoimmune hemolytic anemia
    BIOCHEMICAL

.

    Treatment with high-dose steroids
    MEDICATION

 resulted in

    complete remission
    SYMPTOMS

 within 2 weeks. Study of an additional 72 patients with

    Gaucher's disease
    DIAGNOSIS

 revealed another case of

    Coombs-positive warm-type autoimmune hemolytic anemia
    BIOCHEMICAL

; other

    autoimmune disorders
    DIAGNOSIS

 were found in 17 of these patients. The possible association of

    Coombs-positive hemolytic anemia
    BIOCHEMICAL

 and

    Gaucher's disease
    DIAGNOSIS

 is discussed.

Gaucher's disease
Gaucher's disease
autoimmune disorders
Gaucher's disease


Pulmonary hypertension and Gaucher's disease: logical association or mere coincidence?

A 17-year-old boy with Gaucher's disease died suddenly 2 days after femoral osteotomy. At autopsy, in addition to extensive infiltrates of Gaucher cells in the cirrhotic liver, lymph nodes, and bone marrow, there were high-grade pulmonary arterial hypertensive changes but virtually no Gaucher cells in the lung. Although previous reports have stressed lung infiltrates with capillary plugging by Gaucher cells as important in the pathogenesis of pulmonary hypertension, the present case raises the question of a different mechanism--possibly a circulating vasoactive substance that bypasses the diseased liver.

A

    17-year-old
    AGE

    boy
    GENDER

 with

    Gaucher's disease
    DIAGNOSIS

    died
    SYMPTOMS

    suddenly
    SYMPTOMS

 2 days after

    femoral osteotomy
    MEDICATION

. At

    autopsy
    PARACLINICAL

, in addition to

    extensive infiltrates of Gaucher cells in the cirrhotic liver, lymph nodes, and bone marrow
    MICROSCOPIC

, there were

    high-grade pulmonary arterial hypertensive changes
    SYMPTOMS

 but

    virtually no Gaucher cells in the lung
    NEG_FINDINGS

. Although previous reports have stressed

    lung infiltrates with capillary plugging by Gaucher cells
    MICROSCOPIC

 as important in the pathogenesis of

    pulmonary hypertension
    SYMPTOMS

, the present case raises the question of a different mechanism--possibly a

    circulating vasoactive substance
    BIOCHEMICAL

 that bypasses the diseased

    liver
    BIOCHEMICAL

.


A glucocerebrosidase fusion gene in Gaucher disease. Implications for the molecular anatomy, pathogenesis, and diagnosis of this disorder.

The molecular diagnosis of Gaucher disease has been difficult due to the existence of several different point mutations in the glucocerebrosidase gene and due to the presence of a tightly linked, highly homologous pseudogene. We now report the occurrence of a "Lepore-like" glucocerebrosidase fusion gene in which the 5' end is the functional gene and the 3' end is the pseudogene. This further complicates the molecular diagnosis of Gaucher disease but sheds light on the molecular anatomy of the glucocerebrosidase gene complex and on the pathogenesis of this important storage disease.

The

    molecular diagnosis
    PARACLINICAL

 of

    Gaucher disease
    DIAGNOSIS

 has been difficult due to the existence of

    several different point mutations in the glucocerebrosidase gene
    GENETICS

 and due to the presence of a

    tightly linked, highly homologous pseudogene
    GENETICS

. We now report the occurrence of a

    "Lepore-like" glucocerebrosidase fusion gene in which the 5' end is the functional gene and the 3' end is the pseudogene
    GENETICS

. This further complicates the

    molecular diagnosis
    PARACLINICAL

 of

    Gaucher disease
    DIAGNOSIS

 but sheds light on the molecular anatomy of the

    glucocerebrosidase gene complex
    GENETICS

 and on the pathogenesis of this important

    storage disease
    DIAGNOSIS

.

Gaucher disease
Gaucher disease
storage disease


A further case of Gaucher's disease in a black Zimbabwean.

We present a further case of Gaucher's disease in a 23 year old black Zimbabwean woman treated in Bulawayo. The patient underwent a splenectomy for hypersplenism due to massive splenomegaly. The patient did well post-operatively and has continued to honour her outpatient follow-up appointments. At the last review, 8 months after splenectomy, she still continues to enjoy good health. There was no family history suggestive of Gaucher's disease and there is no possibility that this patient could be related to the other 2 cases (sisters) reported by Muguti et al in 1987.

We present a further case of

    Gaucher's disease
    DIAGNOSIS

 in a

    23 year old
    AGE

    black Zimbabwean
    ETHNICITY

    woman
    GENDER

 treated in

    Bulawayo
    ETHNICITY

. The patient underwent a

    splenectomy
    MEDICATION

 for

    hypersplenism
    BIOCHEMICAL

 due to

    massive splenomegaly
    SYMPTOMS

. The patient did well

    post-operatively
    MEDICATION

 and has continued to honour her outpatient follow-up appointments. At the last review, 8 months after

    splenectomy
    MEDICATION

,

    she
    GENDER

 still

    continues to enjoy good health
    SYMPTOMS

. There was

    no family history suggestive of Gaucher's disease
    NEG_FINDINGS

 and there is no possibility that this patient

    could be related to the other 2 cases (sisters)
    FAMILY

 reported by Muguti et al in 1987.

massive splenomegaly
continues to enjoy good health


Focal changes of the spleen in one case of Gaucher disease--assessed by ultrasonography, CT, MRI and angiography.

Focal lesions of the spleen in one case of Gaucher disease are demonstrated by ultrasonography, CT, MRI and angiography. The sonographic and angiographic features differ from the findings presented in previous reports. The Gaucher manifestations in the spleen as demonstrated by CT, do not seem to have been reported previously. An earlier report on the MR findings in the liver and spleen in this disease did not disclose any focal abnormalities. In this case, ultrasonography and MRI revealed a targetlike configuration of the focal lesions. An attempt is made to analyze the more complex patterns disclosed by MRI against the background of the manifestations by the other imaging modalities and previous reports.

    Focal lesions of the spleen
    SYMPTOMS

 in one case of

    Gaucher disease
    DIAGNOSIS

 are demonstrated by

    ultrasonography
    PARACLINICAL

,

    CT
    PARACLINICAL

,

    MRI
    PARACLINICAL

 and

    angiography
    PARACLINICAL

. The sonographic and angiographic features differ from the findings presented in previous reports. The

    Gaucher manifestations in the spleen
    MICROSCOPIC

 as demonstrated by

    CT
    PARACLINICAL

, do not seem to have been reported previously. An earlier report on the

    MR findings in the liver and spleen
    PARACLINICAL

 in this disease did

    not disclose any focal abnormalities
    NEG_FINDINGS

. In this case,

    ultrasonography
    PARACLINICAL

 and

    MRI
    PARACLINICAL

 revealed a

    targetlike configuration of the focal lesions
    SYMPTOMS

. An attempt is made to analyze the more complex patterns disclosed by

    MRI
    PARACLINICAL

 against the background of the manifestations by the other imaging modalities and previous reports.


[Bone changes in Gaucher disease].

Among Ashkenazi-Jews, Gaucher' disease, an autosomal-recessive hereditary genetic defect of sphingolipid metabolism, occurs more frequently than in the general population. Because of lack of the specific b-glucosidase, glucocerebrosidase, there is increased deposition of glucocerebrosides in the reticulo-endothelial system, mostly in the spleen, liver, and bone-marrow. In the chronic adult form (type 1), in addition to the hematologic complications (which are mostly associated with a splenomegaly), a less known involvement of the skeletal system occurs, which can lead to significant rheumatologic and orthopedic problems. These are: nonspecific skeletal and joint pain, purulent osteomyelitis, pseudo-osteomyelitis, aseptic necrosis of the femoral head, pathologic fractures of the long bones, acutely occurring kyphosis secondary to pathologic vertebral fractures with or without spinal compression, bony deformities, growth disturbances, arthritis, and bursitis. One sees a wide variety of bone lesions which can be solitary or multiple. Various pathogenic mechanisms have been discussed: toxic reaction to the Gaucher cells, disturbance of the osteoblastic and osteoclastic function, compression of osseous blood vessels by pathological cells, pressure-induced atrophy of the surrounding osseous tissue, local hemorrhage, local thrombosis, invasion of the arterioles with subsequent occlusion, and bone infarcts. The therapy is purely symptomatic. For orthopedic problems there is a greater tendency towards conservative treatment. There is disagreement as to whether splenectomy, which is often performed for hematologic or mechanical reasons, accelerates involvement of the bone. The case of a patient with multiple fractures of the spine and a slight spinal compression is presented.

Among

    Ashkenazi-Jews
    ETHNICITY

,

    Gaucher' disease
    DIAGNOSIS

, an

    autosomal-recessive hereditary genetic defect of sphingolipid metabolism
    GENETICS

, occurs more frequently than in the general population. Because of

    lack of the specific b-glucosidase, glucocerebrosidase
    BIOCHEMICAL

, there is

    increased deposition of glucocerebrosides in the reticulo-endothelial system, mostly in the spleen, liver, and bone-marrow
    MICROSCOPIC

. In the

    chronic adult form
    DIAGNOSIS

 (

    type 1)
    DIAGNOSIS

, in addition to the

    hematologic complications
    SYMPTOMS

 (which are mostly associated with a

    splenomegaly
    SYMPTOMS

), a less known

    involvement of the skeletal system
    SYMPTOMS

 occurs, which can lead to significant

    rheumatologic and orthopedic problems
    SYMPTOMS

. These are:

    nonspecific skeletal and joint pain
    SYMPTOMS

,

    purulent osteomyelitis
    DIAGNOSIS

,

    pseudo-osteomyelitis
    DIAGNOSIS

,

    aseptic necrosis of the femoral head
    SYMPTOMS

,

    pathologic fractures of the long bones
    SYMPTOMS

,

    acutely occurring kyphosis secondary to pathologic vertebral fractures with or without spinal compression
    SYMPTOMS

,

    bony deformities
    SYMPTOMS

,

    growth disturbances
    SYMPTOMS

,

    arthritis
    SYMPTOMS

, and

    bursitis
    DIAGNOSIS

. One sees a wide variety of

    bone lesions
    SYMPTOMS

 which can be

    solitary or multiple
    SYMPTOMS

. Various pathogenic mechanisms have been discussed:

    toxic reaction to the Gaucher cells
    MICROSCOPIC

,

    disturbance of the osteoblastic and osteoclastic function
    SYMPTOMS

,

    compression of osseous blood vessels by pathological cells
    SYMPTOMS

,

    pressure-induced atrophy of the surrounding osseous tissue
    SYMPTOMS

,

    local hemorrhage
    SYMPTOMS

,

    local thrombosis
    SYMPTOMS

,

    invasion of the arterioles with subsequent occlusion
    SYMPTOMS

, and

    bone infarcts
    SYMPTOMS

. The therapy is

    purely symptomatic
    MEDICATION

. For

    orthopedic problems
    SYMPTOMS

 there is a greater tendency towards

    conservative treatment
    MEDICATION

. There is disagreement as to whether

    splenectomy
    MEDICATION

, which is often performed for

    hematologic
    MEDICATION

 or mechanical reasons, accelerates

    involvement of the bone
    SYMPTOMS

. The case of a patient with

    multiple fractures of the spine
    SYMPTOMS

 and a

    slight spinal compression
    SYMPTOMS

 is presented.

Gaucher' disease
chronic adult form
type 1)
purulent osteomyelitis
pseudo-osteomyelitis
bursitis

purely symptomatic
conservative treatment
splenectomy
hematologic


Activator protein deficient Gaucher's disease. A second patient with the newly identified lipid storage disorder.

A report is presented based on the biochemical and immunochemical studies of various tissues from a 15-year-old boy with a neuronopathic form of Gaucher's disease. Qualitative and quantitative lipid analyses revealed a storage of glucosylceramide. The striking feature was that, employing the usual assay methods, a normal activity of the lysosomal enzyme glucosylceramidase was revealed, despite massive lipid accumulation. Immunochemical assays of hepatic and splenic tissue extracts from this atypical Gaucher's patient disclosed the absence of A1 activator protein, which is necessary for the enzyme degradation of glucosylceramide in vivo. This is the second documented case of a patient presenting with glucosylceramide activator protein deficiency.

A report is presented based on the

    biochemical and immunochemical studies of various tissues
    PARACLINICAL

 from a

    15-year-old
    AGE

    boy
    GENDER

 with a

    neuronopathic form of Gaucher's disease
    DIAGNOSIS

.

    Qualitative and quantitative lipid analyses
    PARACLINICAL

 revealed a

    storage of glucosylceramide
    MICROSCOPIC

. The striking feature was that, employing the usual assay methods, a

    normal activity of the lysosomal enzyme glucosylceramidase was revealed
    NEG_FINDINGS

,

    despite massive lipid accumulation
    NEG_FINDINGS

.

    Immunochemical assays of hepatic and splenic tissue extracts
    PARACLINICAL

 from this

    atypical Gaucher's
    DIAGNOSIS

 patient disclosed the

    absence of A1 activator protein, which is necessary for the enzyme degradation of glucosylceramide in vivo
    BIOCHEMICAL

. This is the second documented case of a patient presenting with

    glucosylceramide activator protein deficiency
    BIOCHEMICAL

.

neuronopathic form of Gaucher's disease
atypical Gaucher's


Sphingolipid activator protein deficiency in a 16-week-old atypical Gaucher disease patient and his fetal sibling: biochemical signs of combined sphingolipidoses.

We describe a patient who presented shortly after birth with hyperkinetic behaviour, myoclonia, respiratory insufficiency and hepatosplenomegaly. Gaucher-like storage cells were found in bone marrow. A liver biopsy showed massive lysosomal storage morphologically different to that in known lipid storage disorders. Biochemically, the patient had partial deficiencies of beta-galactocerebrosidase, beta-glucocerebrosidase and ceramidase in skin fibroblast extracts, but the sphingomyelinase activity was normal. Glucosyl ceramide and ceramide were elevated in liver tissue. Loading of cultured fibroblasts with radioactive sphingolipid precursors indicated a profound defect in ceramide catabolism. Immunological studies in fibroblasts showed a total absence of cross-reacting material to sphingolipid activator protein 2 (SAP-2). The patient died at 16 weeks of age. The fetus from his mother's next pregnancy was similarly affected. The possibility that the disorder results from a primary defect at the level of SAP-2 is discussed. We have named this unique disorder SAP deficiency.

We describe a patient who presented shortly after

    birth
    AGE

 with

    hyperkinetic behaviour
    SYMPTOMS

,

    myoclonia
    SYMPTOMS

,

    respiratory insufficiency
    SYMPTOMS

 and

    hepatosplenomegaly
    SYMPTOMS

.

    Gaucher-like storage cells were found in bone marrow
    MICROSCOPIC

. A

    liver biopsy
    PARACLINICAL

 showed

    massive lysosomal storage morphologically different to that in known lipid storage disorders
    MICROSCOPIC

. Biochemically, the patient had

    partial deficiencies of beta-galactocerebrosidase, beta-glucocerebrosidase and ceramidase in skin fibroblast extracts
    BIOCHEMICAL

, but the

    sphingomyelinase activity was normal
    NEG_FINDINGS

.

    Glucosyl ceramide and ceramide were elevated in liver tissue
    MICROSCOPIC

.

    Loading of cultured fibroblasts with radioactive sphingolipid precursors
    MICROSCOPIC

 indicated a

    profound defect in ceramide catabolism
    BIOCHEMICAL

.

    Immunological studies in fibroblasts
    PARACLINICAL

 showed a

    total absence of cross-reacting material to sphingolipid activator protein 2 (SAP-2)
    BIOCHEMICAL

. The patient

    died
    SYMPTOMS

 at

    16 weeks of age
    AGE

.

    The fetus from his mother's next pregnancy was similarly affected
    FAMILY

. The possibility that the disorder results from a primary

    defect at the level of SAP-2
    BIOCHEMICAL

 is discussed. We have named this unique disorder

    SAP deficiency
    DIAGNOSIS

.

hyperkinetic behaviour
myoclonia
respiratory insufficiency
hepatosplenomegaly
died


Aseptic necrosis of the capitate secondary to Gaucher's disease: a case report.

We report a case with aseptic necrosis of the capitate in a young patient with Gaucher's disease and no fracture of the carpus. The value of technetium bone scintigraphy and computer tomographic scanning are discussed.

We report a case with

    aseptic necrosis of the capitate
    SYMPTOMS

 in a

    young
    AGE

 patient with

    Gaucher's disease
    DIAGNOSIS

 and

    no fracture of the carpus
    NEG_FINDINGS

. The value of

    technetium bone scintigraphy
    PARACLINICAL

 and

    computer tomographic scanning
    PARACLINICAL

 are discussed.


Pseudo-osteomyelitis in Gaucher's disease.

Gaucher's disease is an uncommon lipid storage disease sometimes associated with bone pain that can mimic an acute pyarthrosis or osteomyelitis. A case report with two incidences of pseudo-osteomyelitis with two-year follow-up is presented along with a literature review. Recommendations for evaluation and differentiation from a true infection are given. In general a needle biopsy for culture is preferable to any open biopsy or drainage if the diagnosis is in doubt.

    Gaucher's disease
    DIAGNOSIS

 is an uncommon

    lipid storage disease
    DIAGNOSIS

 sometimes associated with

    bone pain
    SYMPTOMS

 that can mimic an

    acute pyarthrosis
    SYMPTOMS

 or

    osteomyelitis
    DIAGNOSIS

. A case report with two incidences of

    pseudo-osteomyelitis
    DIAGNOSIS

 with two-year follow-up is presented along with a literature review. Recommendations for evaluation and differentiation from a

    true infection
    DIAGNOSIS

 are given. In general a

    needle biopsy for culture
    PARACLINICAL

 is preferable to any

    open biopsy
    PARACLINICAL

    or drainage
    MEDICATION

 if the diagnosis is in doubt.

Gaucher's disease
lipid storage disease
osteomyelitis
pseudo-osteomyelitis
true infection


Gaucher disease: fate of the splenic remnant after partial splenectomy--a case of rapid enlargement.

In Gaucher disease, partial splenectomy has been suggested for alleviating the complications of splenomegaly as well as for avoiding the immunologic compromise and potential acceleration of bony and hepatic involvement that may follow total splenic resection. However, the fate of the splenic remnant has been reported rarely. A subtotal splenectomy (85%) was performed in a 19-month-old girl with rapidly progressing Gaucher disease and massive splenomegaly (12% of body weight). Within 3 months, the splenic remnant had increased four-fold in size. Previous reports indicated only three Gaucher patients had significant enlargement of the splenic remnant after partial splenectomy. These findings indicate that splenomegaly may recur rapidly in Gaucher disease following partial splenectomy.

In

    Gaucher disease
    DIAGNOSIS

,

    partial splenectomy
    MEDICATION

 has been suggested for alleviating the complications of

    splenomegaly
    SYMPTOMS

 as well as for avoiding the

    immunologic compromise
    SYMPTOMS

 and

    potential acceleration of bony and hepatic involvement
    SYMPTOMS

 that may follow

    total splenic resection
    MEDICATION

. However, the fate of the splenic remnant has been reported rarely. A

    subtotal splenectomy (85%)
    MEDICATION

 was performed in a

    19-month-old
    AGE

    girl
    GENDER

 with

    rapidly progressing Gaucher disease
    DIAGNOSIS

 and

    massive splenomegaly (12% of body weight)
    SYMPTOMS

. Within 3 months,

    the splenic remnant had increased four-fold in size
    SYMPTOMS

. Previous reports indicated only three

    Gaucher
    DIAGNOSIS

 patients had

    significant enlargement of the splenic remnant
    SYMPTOMS

 after

    partial splenectomy
    MEDICATION

. These findings indicate that

    splenomegaly
    SYMPTOMS

 may recur rapidly in

    Gaucher disease
    DIAGNOSIS

 following

    partial splenectomy
    MEDICATION

.

Gaucher disease
rapidly progressing Gaucher disease
Gaucher
Gaucher disease

partial splenectomy
total splenic resection
subtotal splenectomy (85%)
partial splenectomy
partial splenectomy


Oculomotor apraxia: the presenting sign of Gaucher disease.

Oculomotor apraxia may be idiopathic or a symptom of a variety of diseases. In Gaucher disease, oculomotor deficit is characterized by a failure of volitional horizontal gaze with preservation of vertical movements. We present 2 sisters, 6 1/2 and 5 1/2 years of age, in whom the presenting sign was oculomotor apraxia. Oculomotor apraxia has not been previously reported as the presenting manifestation of Gaucher disease.

    Oculomotor apraxia
    SYMPTOMS

 may be

    idiopathic
    DIAGNOSIS

 or a symptom of a variety of diseases. In

    Gaucher disease
    DIAGNOSIS

,

    oculomotor deficit
    SYMPTOMS

 is characterized by a

    failure of volitional horizontal gaze
    NEG_FINDINGS

 with

    preservation of vertical movements
    NEG_FINDINGS

. We present 2 sisters,

    6 1/2 and 5 1/2 years of age
    AGE

, in whom the presenting sign was

    oculomotor apraxia
    SYMPTOMS

.

    Oculomotor apraxia
    SYMPTOMS

 has not been previously reported as the presenting manifestation of

    Gaucher disease
    DIAGNOSIS

.

Oculomotor apraxia
oculomotor deficit
oculomotor apraxia
Oculomotor apraxia

idiopathic
Gaucher disease
Gaucher disease

failure of volitional horizontal gaze
preservation of vertical movements


Spinal cord compression in type I Gaucher disease.

Three patients with epidural compression of the spinal cord, a rare but serious complication of type I Gaucher disease, are described. In two cases the compression occurred at the lower thoracic region due to collapse of T-11 and T-12, respectively. In the third case, an epidural mass developed at the dorsal aspect of the cord at T-2, and T-2 and T-3 showed diffuse infiltration without collapse. In two cases the diagnosis was made with magnetic resonance (MR) imaging. In these cases MR imaging proved to be a safe, accurate method for demonstrating the nature and extent of disease within the spinal canal.

Three patients with

    epidural compression of the spinal cord
    SYMPTOMS

, a rare but serious complication of

    type I Gaucher disease
    DIAGNOSIS

, are described. In two cases the

    compression occurred at the lower thoracic region
    SYMPTOMS

 due to

    collapse of T-11 and T-12
    SYMPTOMS

, respectively. In the third case, an

    epidural mass developed at the dorsal aspect of the cord at T-2
    SYMPTOMS

, and

    T-2 and T-3 showed diffuse infiltration without collapse
    SYMPTOMS

. In two cases the diagnosis was made with

    magnetic resonance (MR) imaging
    PARACLINICAL

. In these cases

    MR imaging
    PARACLINICAL

 proved to be a safe, accurate method for demonstrating the nature and extent of disease within the spinal canal.


[Splenic artery aneurysm in a patient with Gaucher's disease].

We present a 31-year-old woman suffering from Gaucher's disease in whom during splenectomy a big splenic artery aneurysm was found, 5 x 3.5 cm in diameters; it was due to hypersplenism and compression of the enlarged spleen. In a huge spleen 43 cm in length and 5420 grams in weight, many deposits of glycocerebrosides were found. Cholecystectomy was also carried out for calculous cholecystitis. The recovery was uneventful and the patient stayed in good condition.

We present a

    31-year-old
    AGE

    woman
    GENDER

 suffering from

    Gaucher's disease
    DIAGNOSIS

 in whom during

    splenectomy
    MEDICATION

 a

    big splenic artery aneurysm was found, 5 x 3.5 cm in diameters
    SYMPTOMS

; it was due to

    hypersplenism
    BIOCHEMICAL

 and

    compression of the enlarged spleen
    SYMPTOMS

. In a

    huge spleen 43 cm in length
    SYMPTOMS

 and

    5420 grams in weight
    SYMPTOMS

,

    many deposits of glycocerebrosides were found
    MICROSCOPIC

.

    Cholecystectomy
    MEDICATION

 was also carried out for

    calculous cholecystitis
    DIAGNOSIS

. The recovery was uneventful and the patient stayed in good condition.

Gaucher's disease
calculous cholecystitis


[Splenectomy in Gaucher's disease. Apropos of 2 cases, one of which was preceded by embolization].

Two cases of Gaucher's disease type I are reported Splenectomy was indicated because of hypersplenism and massive splenomegaly. In one case hypersplenism was treated with pre-operative selective embolization because of the volume of the spleen (20 kg). The embolization corrected the thrombopenia but not the size of the spleen. Four years after operation for case 1 and eight months for case two, there is an improvement in the clinical status.

Two cases of

    Gaucher's disease type I
    DIAGNOSIS

 are reported

    Splenectomy
    MEDICATION

 was indicated because of

    hypersplenism
    BIOCHEMICAL

 and

    massive splenomegaly
    SYMPTOMS

. In one case

    hypersplenism
    BIOCHEMICAL

 was treated with

    pre-operative selective embolization
    MEDICATION

 because of the volume of the spleen (20 kg). The

    embolization
    MEDICATION

    corrected the thrombopenia
    BIOCHEMICAL

    but not the size of the spleen
    NEG_FINDINGS

. Four years after operation for case 1 and eight months for case two, there is an

    improvement in the clinical status
    SYMPTOMS

.

Splenectomy
pre-operative selective embolization
embolization

hypersplenism
hypersplenism
corrected the thrombopenia

massive splenomegaly
improvement in the clinical status


[A case of Gaucher's disease associated with peripheral retinal ischemia].

A 24 years old girl affected by Gaucher's disease showed a wide peripheral retinal vascular ischemia with new vessel. This could be either a fortuitous association between a Gaucher's disease and Eales' syndrome or an ocular complication of Gaucher's disease not previously described. A symptomatic panretinalphotocoagulation has been performed and resulted in new vessels involution.

A

    24 years old
    AGE

    girl
    GENDER

 affected by

    Gaucher's disease
    DIAGNOSIS

 showed a

    wide peripheral retinal vascular ischemia with new vessel
    SYMPTOMS

. This could be either a fortuitous association between a

    Gaucher's disease and Eales' syndrome
    DIAGNOSIS

 or an

    ocular complication
    DIAGNOSIS

 of

    Gaucher's disease
    DIAGNOSIS

 not previously described. A

    symptomatic panretinalphotocoagulation
    MEDICATION

 has been performed and resulted in

    new vessels involution
    SYMPTOMS

.

Gaucher's disease
Gaucher's disease and Eales' syndrome
ocular complication
Gaucher's disease


[Gaucher's disease and pregnancy].

The authors describe a female patient with a chronic pattern of Gaucher's disease which remained unrecognized for a long time. Pregnancy was noted to affect the disease progress and development of liver cellular failure as well as the hemorrhagic syndrome. Splenectomy gave rise to a stable disease remission followed by normal pregnancy and delivery.

The authors describe a

    female
    GENDER

 patient with a

    chronic pattern of Gaucher's disease
    DIAGNOSIS

 which

    remained unrecognized for a long time
    NEG_FINDINGS

.

    Pregnancy
    SYMPTOMS

 was noted to affect the disease progress and development of

    liver cellular failure
    SYMPTOMS

 as well as the

    hemorrhagic syndrome
    SYMPTOMS

.

    Splenectomy
    MEDICATION

 gave rise to a

    stable disease remission
    MEDICATION

 followed by

    normal pregnancy and delivery
    SYMPTOMS

.

Pregnancy
liver cellular failure
hemorrhagic syndrome
normal pregnancy and delivery


Histiocytic diseases of bone marrow.

The disease most likely to be associated with large numbers of bone marrow storage histiocytes is Gaucher's disease. In our community of western Pennsylvania, eastern Ohio, and West Virginia, we have encountered 30 patients with Gaucher's disease during the past 25 years. During the same 25 years, a group of about 20 other patients have been examined for storage cells caused by diseases other than Gaucher's disease. These other conditions are associated with smaller numbers of storage cells, and these patients require a more extensive examination that should include serum or tissue lipid analyses, enzymology, and electron microscopy to assist in the diagnosis.

The disease most likely to be associated with

    large numbers of bone marrow storage histiocytes
    MICROSCOPIC

 is

    Gaucher's disease
    DIAGNOSIS

. In our community of

    western Pennsylvania
    ETHNICITY

,

    eastern Ohio
    ETHNICITY

, and

    West Virginia
    ETHNICITY

, we have encountered 30 patients with

    Gaucher's disease
    DIAGNOSIS

 during the past 25 years. During the same 25 years, a group of about 20 other patients have been examined for

    storage cells
    MICROSCOPIC

 caused by diseases other than

    Gaucher's disease
    DIAGNOSIS

. These other conditions are associated with

    smaller numbers of storage cells
    MICROSCOPIC

, and these patients require a more extensive examination that should include

    serum or tissue lipid analyses
    PARACLINICAL

,

    enzymology
    PARACLINICAL

, and

    electron microscopy
    PARACLINICAL

 to assist in the diagnosis.

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

western Pennsylvania
eastern Ohio
West Virginia


[Gaucher disease and pregnancy].

Two pregnancies in a patient with Gaucher's disease type I are reported. Anemia and thrombocytopenia were augmented during pregnancy, but no effect on the spleen and liver was observed. The first delivery was associated with a severe post partum haemorrhagia (platelet count 56,000/mcl, hemoglobin before delivery 10.2 g/100 ml, postpartum 5.5 g/100ml). At the end of the second pregnancy the platelet count was 33,000/mcl. Platelet transfusions were given after induction of preterm labor and no bleeding complications were observed. The obstetric aspects of Gaucher's disease are reviewed. Post partum haemorrhagia is associated with thrombopenia and is observed in patients with platelet counts under 100,000/mcl. Platelet infusions are recommended before delivery in these patients. Thrombocytopenic patients should be carefully monitored during labor with crossmatched blood on standby.

Two

    pregnancies
    DIAGNOSIS

 in a patient with

    Gaucher's disease type I
    DIAGNOSIS

 are reported.

    Anemia
    BIOCHEMICAL

 and

    thrombocytopenia
    BIOCHEMICAL

 were augmented during

    pregnancy
    DIAGNOSIS

, but

    no effect on the spleen and liver was observed
    NEG_FINDINGS

. The first delivery was associated with a

    severe post partum haemorrhagia (platelet count 56,000/mcl, hemoglobin before delivery 10.2 g/100 ml, postpartum 5.5 g/100ml)
    SYMPTOMS

. At the end of the second

    pregnancy
    DIAGNOSIS

 the

    platelet count was 33,000/mcl
    BIOCHEMICAL

.

    Platelet transfusions
    MEDICATION

 were given after

    induction of preterm labor
    MEDICATION

 and

    no bleeding complications
    NEG_FINDINGS

 were observed. The obstetric aspects of

    Gaucher's disease
    DIAGNOSIS

 are reviewed.

    Post partum haemorrhagia
    SYMPTOMS

 is associated with

    thrombopenia
    BIOCHEMICAL

 and is observed in patients with

    platelet counts under 100,000/mcl
    BIOCHEMICAL

.

    Platelet infusions
    MEDICATION

 are recommended before

    delivery
    MEDICATION

 in these patients.

    Thrombocytopenic
    BIOCHEMICAL

 patients should be carefully monitored during labor with

    crossmatched blood on standby
    PARACLINICAL

.

pregnancies
Gaucher's disease type I
pregnancy
pregnancy
Gaucher's disease

Anemia
thrombocytopenia
platelet count was 33,000/mcl
thrombopenia
platelet counts under 100,000/mcl
Thrombocytopenic

Platelet transfusions
induction of preterm labor
Platelet infusions
delivery


Pseudo-Gaucher cells preceding the appearance of immunoblastic lymphoma.

A 49-year-old white woman who presented with multiple lytic bone lesions was found to have Gaucher-like storage cells in multiple bone marrow aspirates and a percutaneous bone marrow biopsy several months before the development of overt disseminated lymphoma. Open bone biopsies of three different sites at initial presentation revealed only necrotic debris and a nondiagnostic polymorphic infiltrate. Elevated leukocyte beta-glucocerebrosidase levels ruled out the diagnosis of classic Gaucher's disease. The ultrastructural characteristics of these storage cells were found to be identical to those of pseudo-Gaucher cells found in patients with chronic myelogenous leukemia and distinctly different from those previously reported in other non-Hodgkin's lymphoma or plasma cell dyscrasias. A possible pathogenetic mechanism is suggested.

A

    49-year-old
    AGE

    white
    ETHNICITY

    woman
    GENDER

 who presented with

    multiple lytic bone lesions
    SYMPTOMS

 was found to have

    Gaucher-like storage cells in multiple bone marrow aspirates
    MICROSCOPIC

 and a

    percutaneous bone marrow biopsy
    PARACLINICAL

 several months before the development of

    overt disseminated lymphoma
    DIAGNOSIS

.

    Open bone biopsies of three different sites
    PARACLINICAL

 at initial presentation revealed

    only necrotic debris
    MICROSCOPIC

 and a

    nondiagnostic polymorphic infiltrate
    NEG_FINDINGS

.

    Elevated leukocyte beta-glucocerebrosidase levels
    BIOCHEMICAL

    ruled out the diagnosis of classic Gaucher's disease
    NEG_FINDINGS

. The

    ultrastructural characteristics of these storage cells were found to be identical to those of pseudo-Gaucher cells found in patients with chronic myelogenous leukemia
    MICROSCOPIC

 and distinctly different from those previously reported in other

    non-Hodgkin's lymphoma
    NEG_FINDINGS

 or

    plasma cell dyscrasias
    MICROSCOPIC

. A possible pathogenetic mechanism is suggested.


An immunoelectron microscopic study of glucocerebrosidase in type 1 Gaucher's disease spleen.

An immunogold labeling procedure was applied to ultrathin cryosections and used to study the subcellular localization of glucocerebrosidase in lipid-laden "Gaucher cells" in spleen from a patient with type 1 Gaucher's disease. Glucocerebrosidase protein was associated with the characteristic stored lipid material in large, irregularly shaped vacuoles. As shown by double labeling, the storage vacuoles contained not only glucocerebrosidase protein but also other lysosomal enzymes. Thus the storage vacuoles can be considered to be secondary lysosomes. The findings indicate that although glucocerebrosidase was present in secondary lysosomes in this patient, the activity of the mutant enzyme was insufficient to prevent storage of glucocerebroside in the spleen.

An

    immunogold labeling procedure
    PARACLINICAL

 was applied to

    ultrathin cryosections
    PARACLINICAL

 and used to study the

    subcellular localization of glucocerebrosidase in lipid-laden "Gaucher cells" in spleen
    MICROSCOPIC

 from a patient with

    type 1 Gaucher's disease
    DIAGNOSIS

.

    Glucocerebrosidase protein was associated with the characteristic stored lipid material in large, irregularly shaped vacuoles
    MICROSCOPIC

. As shown by

    double labeling
    PARACLINICAL

,

    the storage vacuoles contained not only glucocerebrosidase protein but also other lysosomal enzymes
    MICROSCOPIC

. Thus

    the storage vacuoles
    MICROSCOPIC

 can be considered to be

    secondary lysosomes
    MICROSCOPIC

. The findings indicate that although

    glucocerebrosidase was present in secondary lysosomes
    MICROSCOPIC

 in this patient,

    the activity of the mutant enzyme was insufficient to prevent storage of glucocerebroside in the spleen
    NEG_FINDINGS

.


[Scintigraphic picture in Gaucher's disease].

The paper is devoted to analysis of the results of combined radionuclide investigation of the liver, spleen, kidneys, lymph nodes and bones in a patient with Gaucher's disease. Scintigraphy was shown to be an important method for making correct diagnosis in patients with this rare disease.

The paper is devoted to analysis of the results of

    combined radionuclide investigation of the liver, spleen, kidneys, lymph nodes and bones
    PARACLINICAL

 in a patient with

    Gaucher's disease
    DIAGNOSIS

.

    Scintigraphy
    PARACLINICAL

 was shown to be an important method for making correct diagnosis in patients with this

    rare disease
    DIAGNOSIS

.


Collodion babies with Gaucher's disease.

Two neonates with acute infantile cerebral Gaucher's disease had prominent collodion skin. Ichthyosis has been described in some cases of metabolic lipid disorders, however, this is the first report of the association of lamellar desquamation of the newborn (collodion baby) with Gaucher's disease.

Two

    neonates
    AGE

 with

    acute infantile cerebral Gaucher's disease
    DIAGNOSIS

 had

    prominent collodion skin
    SYMPTOMS

.

    Ichthyosis
    SYMPTOMS

 has been described in some cases of

    metabolic lipid disorders
    DIAGNOSIS

, however, this is the first report of the association of

    lamellar desquamation of the newborn (collodion baby)
    SYMPTOMS

 with

    Gaucher's disease
    DIAGNOSIS

.