Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (428 page)

   Other Considerations

Histochemical evidence of glycogen storage in muscle is supportive of a glycogen storage disorder but not specific for Pompe disease. CK, AST, ALT, and LDH if elevated, may be useful in the initial evaluation of a patient but must be considered nonspecific.

Suggested Readings

ACMG Work Group on Management of Pompe Disease. Pompe disease diagnosis and management guideline.
Genet Med.
2006;8(5):382.

Tinkle BT, Leslie N. Glycogen storage disease type II (Pompe Disease). In: Pagon RA, Bird TC, Dolan CR, et al., eds.
GeneReviews [Internet]
. Seattle, WA: University of Washington, Seattle; 1993–2007 Aug 31 [updated 2010 Aug 12].

GM
₁
GANGLIOSIDOSIS (LANDING DISEASE, SYSTEMIC LATE INFANTILE LIPIDOSIS, BETA-GALACTOSIDASE-1 DEFICIENCY)

MIM #230500

   Definition

GM
₁
gangliosidosis is an autosomal recessive lysosomal storage disease characterized by accumulation of ganglioside substrates in lysosomes due to a deficiency of beta-galactosidase-1 (GLB1).

   Classification

The three main clinical presentations have variable residual beta-galactosidase activity and show different degrees of neurodegeneration and skeletal abnormalities.

   Type I, or infantile form, shows rapid psychomotor deterioration within 6 months of birth, generalized CNS involvement, hepatosplenomegaly, facial dysmorphism, macular cherry-red spots, skeletal dysplasia, and early death.

   Type II, or late-infantile/juvenile form, has onset between 7 months and 3 years, shows generalized CNS involvement with psychomotor deterioration, seizures, localized skeletal involvement, and survival into childhood. Hepatosplenomegaly and cherry-red spots are usually not present.

   Type III, or adult/chronic form, onsets from 3 to 30 years and is characterized by skeletal involvement and localized CNS abnormalities, such as dystonia or gait or speech disturbance. There is an inverse correlation between disease severity and residual enzyme activity.

   Relevant Tests and Diagnostic Value

   Assay of lysosomal acid beta-galactosidase enzyme in leukocytes, cultured fibroblasts, or brain tissue

   Prenatal diagnosis by enzyme assay in cultured amniotic fluid cells or by HPLC analysis of galactosyl oligosaccharides in amniotic fluid

   Sequence analysis of gene mutations

   Other Considerations

   Tissue biopsy or culture of marrow or skin fibroblasts shows accumulation of GM
₁
ganglioside.