The primary presentations of
neuromuscular disease in the newborn period are
hypotonia and weakness. Although metabolic
myopathies are inherited disorders that present from birth and may present with subtle to marked
neonatal hypotonia, a number of these defects are diagnosed classically in childhood, adolescence, or adulthood. Disorders of
glycogen,
lipid, or mitochondrial metabolism may cause three main clinical syndromes in muscle, namely, (1) progressive weakness with
hypotonia (e.g.,
acid maltase, debrancher
enzyme, and brancher
enzyme deficiencies among the
glycogenoses;
carnitine uptake and
carnitine acylcarnitine translocase defects among the
fatty acid oxidation (FAO) defects; and
cytochrome oxidase deficiency among the
mitochondrial disorders) or (2) acute, recurrent, reversible muscle dysfunction with exercise intolerance and acute muscle breakdown or
myoglobinuria (with or without
cramps), e.g.,
phosphorylase,
phosphofructokinase, and
phosphoglycerate kinase among the
glycogenoses and
carnitine palmitoyltransferase II deficiency among the disorders of FAO or (3) both (e.g., long-chain or very long-chain
acyl coenzyme A (
CoA)
dehydrogenase, short-chain L-
3-hydroxyacyl-CoA dehydrogenase, and trifunctional
protein deficiencies among the FAO defects). Episodes of exercise-induced
myoglobinuria tend to present in later childhood or adolescence; however,
myoglobinuria in the first year of life may occur in FAO disorders during catabolic crises precipitated by fasting or
infection. The following is a survey of
genetic disorders of
glycogen and lipid metabolism resulting in
myopathy, focusing primarily on those defects, to date, that have presented in the neonatal or early infancy period. Disorders of mitochondrial metabolism are discussed in another chapter.