Neuromuscular presentation of severe neonatal onset glycogenosis type IV

Abstract

Glycogen storage disorder type IV (GSD IV) or Andersen disease is a rare autosomal recessive disorder resulting from deficiency of glycogen branching enzyme (GBE). It is very heterogeneous in its clinical features, age of onset, and tissue involvement; classic GSD IV is rapidly progressive and dominated by cirrhosis and hepatic failure. We report a newborn male with severe hypotonia, poor respiratory effort, and elevated CK. The differential included spinal muscular atrophy, congenital muscular dystrophy/myopathy, hypoxia‐ischemia, and chromosomal disorder. Muscle biopsy at 3 weeks of life was remarkable for sarcoplasmic vacuoles with crystalline/granular, diastase‐resistant PAS positive material, and markedly increased acid phosphatase reaction. Ultrastructural examination showed two types of sarcoplasmic inclusions: membrane‐bound with granular and filamentous material, and non‐membrane bound with filamentous to crystalline material. These findings suggested a lysosomal storage disorder other than GSD II (Pompe's disease). Review of literature suggested that clinical and pathological findings might be consistent with the fatal infantile form of GSD IV. Biochemical testing showed markedly decreased muscle GBE activity, consistent with GSD IV. The rare neuromuscular form of GSD IV should be considered in the differential diagnosis of severe congenital, or neonatal/infantile hypotonia.