Gaucher Disease


BACKGROUND:

Gaucher disease is the most common genetic lysosomal storage disorder. It is caused by mutations in the glucocerebrosidase gene and is inherited as an autosomal recessive disorder. Deficiency of this enzyme activity results in accumulation of glucocerebrosides in reticuloendothelial cells with main involvement of the spleen, liver and bones. The disease is classified in three clinical forms: Type 1 (adult nonneuronopathic) is the most common form and is characterized by lack of central nervous system involvement. It is quite heterogeneous in its clinical picture varying from no obvious symptoms to devastating disease. Clinical features include hepatosplenomegaly, thrombocytopenia bone pain and fractures, and anemia. The disorder is especially common in Ashkenazi Jews where the carrier frequency is 1:10 individuals. Type 2 (infantile neuronopathic and Type 3 (juvenile neuropathic) are rare (an incidence in all ethnic groups of 1 affected:100,000 individuals), progressive, and characterized by severe neurological manifestations.

INDICATIONS FOR TESTING:

  • Painless splenomegaly developing into hypersplenism with thrombocytopenia and anemia.

  • Family history.

  • Ashkenazi Jewish Ancestry

SAMPLE REQUIREMENTS:

Blood: Two 5 ml purple top (EDTA) vacutainers of whole blood inverted several times to mix. Forward within 48 hours at room temperature.

Amniotic Fluid: 10-15 ml amniotic fluid from 14th-17th week of gestation or one confluent flask of cultured cells. Send specimen refrigerated, but not frozen (do not ship on dry ice). Please use an overnight courier service.

INTERPRETATION:

PCR based assays are used to detect the three mutations most commonly found in the Ashkenazi Jewish population. The following table shows the prevalence of these alleles among Jewish vs. non Jewish patients:

 

N370S

L444P

84GG

Total Mutations
Detected

Ashkenazi Jews

75%

5%

15%

95%

Others

23%

31%

0%

54%

Report includes background information, results of mutation analysis and assessment of residual risk if results are negative.

COUNSELING ISSUES:

  1. Disease phenotypes vary widely, even when the same mutation is involved.

  2. Parents of affected children are assumed to be carriers. However, some N370S/N370S homozygotes are asymptomatic, so it may be informative to obtain genotypes on parents of affected individuals.

  3. Reliable information regarding Ashkenazi ancestry is important for accurate residual carrier determination when mutations are not detected.

 

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