Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (426 page)

   Blood uric acid >5.0 mg/dL (reference range: 2.0–5.0 mg/dL)

   Triglycerides >250 mg/dL (reference range: 150–200 mg/dL)

   Cholesterol >200 mg/dL (reference range: 100–200 mg/dL)

Biochemical testing:

   Glucose-6-phosphatase enzyme activity in the liver: In most individuals with type Ia disease, the activity of the glucose-6-phosphatase is <10% (normal is 3.50 ± 0.8 μmol/minute/g tissue). In rare individuals with higher residual enzyme activity and milder clinical manifestations, the enzyme activity could be higher (>1.0 μmol/minute/g tissue).

   Glucose-6-phosphate translocase (transporter) activity: Most clinical diagnostic laboratories refrain from offering this enzyme activity assay because fresh (unfrozen) liver is often needed to assay enzyme activity accurately.

Molecular testing:

The two genes known to be associated with type I disease are
G6PC
(type Ia) and
SLC37A4
(type Ib). Mutations in
G6PC
(type Ia) are responsible for 80% of GSD type I, while mutations in the
SLC37A4
(type Ib) transporter gene are responsible for 20% of GSD type I.

   Targeted mutation analysis

   
G6PC
gene: Arg83Cys and Gln347X or larger panels of mutations

   
SLC37A4
gene: Trp118Arg, 1042_1043delCT, and Gly339Cys

   Gene sequence analysis

   
G6PC:
Detects mutations in up to 100% of affected individuals in some homogeneous populations, but in mixed populations (e.g., in the United States), the detection rate is approximately 94%.

   
SLC37A4:
Detects mutations in up to 100% of affected individuals in some homogeneous populations, but in mixed populations (e.g., in the United States), the detection frequency could be lower because both mutations may not be detected in some individuals.

Suggested Readings

Bali DS, Chen YT. Glycogen storage disease type I. In: Pagon RA, Bird TC, Dolan CR, et al., eds.
GeneReviews [Internet]
. Seattle, WA: University of Washington, Seattle; 1993–2006 Apr 19 [updated 2008 Sep 02].

Ekstein J, Rubin BY, Anderson SL, et al. Mutation frequencies for glycogen storage disease Ia in the Ashkenazi Jewish population.
Am J Med Genet.
2004;129A:162–164.

GLYCOGEN STORAGE DISEASE, TYPE II (POMPE DISEASE; ACID ALPHA-GLUCOSIDASE DEFICIENCY; ACID MALTASE DEFICIENCY)

MIM #606800

   Definition