A neonate develops severe hypoglycemia unresponsive to glucagon. Glycerol infusion corrects blood glucose transiently. Liver biopsy shows reduced but not absent glycogen stores. Enzyme studies identify a defect in the muscle-specific phosphorylase b kinase alpha subunit gene (PHKA1). What would be the expected finding in the RED BLOOD CELLS of this patient?
- A Normal phosphorylase b kinase activity ✓
- B Reduced phosphorylase b kinase activity
- C Elevated glucose-6-phosphate
- D Increased glycogen-branching enzyme activity
Explanation
Phosphorylase b kinase is a heterotetramer composed of alpha, beta, gamma, and delta subunits encoded by different genes with tissue-specific isoforms. The PHKA1 gene encodes the muscle-specific alpha subunit; mutations affect only muscle, not liver or erythrocytes. The liver-specific alpha subunit is encoded by PHKA2 (X-linked liver glycogenosis, GSD IXa). Since the mutation is tissue-specific to muscle, erythrocyte phosphorylase b kinase activity (which uses a different isoform) would be normal. This tissue specificity of enzyme isoforms is a critical concept in glycogen storage diseases that determines which enzyme assay is diagnostically valid.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.