Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (436 page)

   A Dachshund canine model of Sanfilippo syndrome type A is available.

Suggested Readings

Esposito S, Balzano N, Daniele A, et al. Heparan N-sulfatase gene: two novel mutations and transient expression of 15 defects.
Biochim Biophys Acta.
2000;1501:1–11.

Schmidt R, von Figura K, Paschke E, et al. Sanfilippo’s disease type A: sulfamidase activity in peripheral leukocytes of normal, heterozygous and homozygous individuals.
Clin Chim Acta.
1977;80:7–16.

TAY-SACHS DISEASE (GM
₂
GANGLIOSIDOSIS, TYPE I; HEXOSAMINIDASE A DEFICIENCY)

MIM #272800

   Definition

Tay-Sachs disease is an autosomal recessive lysosomal storage disease caused by mutations in the alpha subunit of the hexosaminidase A (
HEXA
) gene (15q23). It occurs predominantly in Ashkenazi Jews, French Canadians, and Cajuns.

   Who Should Be Suspected?

This disease is a progressive neurologic disorder which, in the classic infantile form, is characterized by psychomotor deterioration, blindness, macula cherryred spot, and an exaggerated extension response to sound, with death usually by age 2 years. There is also a juvenile form (with death by age 15) and a chronic form in adults.

   Relevant Tests and Diagnostic Value

   Enzyme assay for HEXA in serum, plasma, leukocytes, and cultured amniotic cells and skin fibroblasts

   Sequencing for mutation analysis

   Accumulation of ganglioside GM
₂
in the brain

   Other Considerations

Macula cherry-red spots appear only in the infantile form. Pseudodeficiency alleles 739C-T and 745C-T cause reduced HEXA activity but do not cause illness, and serum acid phosphatase is normal.

Suggested Reading

De Braekeleer M, Hechtman P, Andermann E, et al. The French Canadian Tay-Sachs disease deletion mutation: identification of probable founders.
Hum Genet.
1992;89:83–87.

WOLMAN DISEASE (CHOLESTERYL ESTER STORAGE DISEASE, LAL DEFICIENCY, CHOLESTERYL ESTER HYDROLASE DEFICIENCY)

MIM #278000

   Definition

Wolman disease is an autosomal recessive disorder resulting from the deficiency of lysosomal acid lipase (LIPA; LAL) activity, causing accumulation of total cholesterol and triglycerides throughout body tissues. Two major disorders, the severe infantile-onset Wolman disease and the milder late-onset cholesteryl ester storage disease (CESD), are caused by mutations in different parts of the LIPA gene (10q23.21).

   Relevant Tests and Diagnostic Value

   Sequence analysis of the LIPA gene for mutations