Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (433 page)

Suggested Reading

Sukegawa K, Nakamura H, Kato Z, et al. Biochemical and structural analysis of missense mutations in N-acetylgalactosamine-6-sulfate sulfatase causing mucopolysaccharidosis IVA phenotypes.
Hum Mol Genet.
2000;9:1283–1290.

MUCOLIPIDOSIS III (
N
-ACETYLGLUCOSAMINE-1-PHOSPHATE TRANSFERASE DEFICIENCY; PSEUDO-HURLER DYSTROPHY)

MIM #252600

Definition

Mucolipidosis III alpha/beta (classic pseudo-Hurler polydystrophy) is caused by mutation in the gene encoding the alpha/beta-subunits precursor gene of
N
-acetylglucosamine-1-phosphotransferase (GNPTAB; GlcNAcphosphotransferase; 12q23). The clinical features of autosomal recessive type III mucolipidosis resemble those of Hurler syndrome but without increased mucopolysaccharides in urine due to a defect in recognition or catalysis and uptake of certain lysosomal enzymes due to deficient activity of
N
-acetylglucosamine-1phosphotransferase.

   Relevant Tests and Diagnostic Value

   Enzyme assay in fibroblasts or leukocytes

   Sequence analysis of the
GNPTAB
gene

   Other Considerations

   Mucolipidosis II alpha/beta, or I-cell disease, is also caused by mutations in the GNPTAB gene.

   Mucolipidosis II has been renamed mucolipidosis II alpha/beta, mucolipidosis IIIA has been renamed mucolipidosis III alpha/beta, and mucolipidosis IIIC has been renamed mucolipidosis III gamma.

Suggested Reading

Bargal R, Zeigler M, Abu-Libdeh B, et al. When mucolipidosis III meets mucolipidosis II: GNPTA gene mutations in 24 patients.
Mol Genet Metab.
2006;88:359–363.

NIEMANN-PICK DISEASE, TYPES A AND B (SPHINGOMYELINASE DEFICIENCY)

MIM #257200

   Definition and Classification

   Niemann-Pick disease (NPD) types A and B are allelic autosomal recessive disorders that result from a deficiency of acid sphingomyelinase (ASM; also called sphingomyelin phosphodiesterase, SMPD1) and the subsequent accumulation of sphingomyelin in lysosomes of the macrophage and monocytes.

   Type A (NPD-A) is neuronopathic with death in early childhood.

   Type B (NPD-B) is nonneuronopathic.

   Relevant Tests and Diagnostic Value