Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (424 page)

   α-Galactosidase measurement in blood cells in male patients.

   Sequence analysis of the
GLA
gene (Xq22.1) is clinically available. Females should have DNA testing, as enzyme assay testing is not generally useful for diagnosing Fabry disease in females.

   Measurement of globotriaosylceramide (Gb3) increased concentrations of globotriaosylceramide (Gb3).

   Other Considerations

Enzyme replacement therapy is available.

Suggested Reading

Aerts JM, Groener JE, Kuiper S, et al. Elevated globotriaosylsphingosine is a hallmark of Fabry disease.
Proc Nat Acad Sci U S A.
2008;105:2812–2817.

FARBER DISEASE (FARBER LIPOGRANULOMATOSIS; ACID CERAMIDASE DEFICIENCY)

MIM #22800

   Definition

This disease is a rare autosomal recessive lysosomal storage disease caused by deficiency of acid ceramidase (also called
N
-acylsphingosine amidohydrolase). Mutations in the acid ceramidase gene, located at 8p22, result in a defect in glycolipid degradation (ceramide), causing accumulation of ceramide, leading to abnormalities in the joints, liver, throat, tissues, and CNS.

   Classification

Type 1 (classic)
: The diagnosis can be made by noting the triad of subcutaneous nodules, arthritis, and laryngeal involvement.

Types 2 and 3
: Patients survive longer. The liver and lung appear not to be involved. Normal intelligence in many of these patients and the postmortem findings suggest that brain involvement is limited or not present. Several patients with type 3 disease may survive in relatively stable condition well into the second decade.

Type 4
: Patients present with hepatosplenomegaly and severe disability in the neonatal period and die before 6 months of age. Massive histiocytic infiltration of the liver, spleen, lungs, thymus, and lymphocytes is found at autopsy.

Type 5
: Characterized particularly by psychomotor deterioration beginning at age 1–2.5 years.

   Relevant Tests and Diagnostic Value

Biochemical testing:

   Enzyme assay: Acid ceramidase assay of skin fibroblasts.

   Analyte: based on giving cultured cells
¹⁴
C-stearic acid sulfatide and determining the amount of radiolabeled ceramide accumulating in cultured cells after 3 days.

   Histologic appearance is granulomatous. In the nervous system, both neurons and glial cells are swollen with stored material characteristic of nonsulfonated acid mucopolysaccharide.

Molecular testing:

   Sequence analysis: Analysis of the entire coding region of the
ASAH
gene

Suggested Readings

Li CM, Park JH, He X, et al. The human acid ceramidase gene (ASAH): structure, chromosomal location, mutation analysis and expression.
Genomics.
2000;62:223–231.