deficiency This is a disease of infancy marked by episodes of Reye-like syndrome, hypoketotic hypoglycemia, lipid storage myopathy, cardiomyopathy, and sometimes sudden death.
deficiency This presents as an episodic disorder such as the one described previously, long-chain hydroxyacyl-CoA dehydrogenase deficiency (HAD), but its onset is in adolescence. Recurrent attacks may be associated with myoglobinuria.
Multiple acyl-CoA dehydrogenase deficiency; glutaric aciduria type II Some cases are caused by a deficiency of electron transfer flavoprotein (ETF) and others by a deficiency of electron transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO). In the severest form of multiple acyl-CoA dehydrogenase deficiency (MADD), infants are born prematurely and many die within the first week of life; added to the common metabolic abnormalities are multiple congenital defects and a characteristic “sweaty feet” odor. In less severe cases, the congenital anomalies are absent. In the least severe form, the onset may be in late infancy (with episodic metabolic disturbances) or in childhood or adult life (with a lipid storage myopathy and a deficiency of serum and muscle carnitine). The prenatal diagnosis of glutaric aciduria type II (GA II) is suggested by the finding of large amounts of glutaric acid in the amniotic fluid. In the milder forms of the disease, oral riboflavin (100 to 300 mg/d) may be helpful.
Muscle coenzyme Q10 deficiency This condition presents as a slowly progressive lipid storage myopathy from early childhood. The basic defect is in coenzyme Q10 in the respiratory chain of muscle mitochondria. The administration of coenzyme Q10 has improved the myopathic weakness.
Neutral lipid storage diseases (Chanarin-Dorfman disease, PNPLA2 mutation) These abnormalities of lipid metabolism are distinct from the beta-oxidation defects; they occur in 2 forms, Chanarin disease, which is characterized by ichthyosis, and a form without skin changes. A progressive myopathy is combined with neurologic manifestations, such as developmental delay, ataxia, neurosensory hearing loss, and microcephaly. The lipid material is stored in muscle as triglyceride droplets that are nonlysosomal and non–membrane-bound.
Several myopathic diseases are related to alterations in thyroid function: (1) chronic thyrotoxic myopathy; (2) exophthalmic ophthalmoplegia (infiltrative orbital ophthalmopathy—Graves disease); (3) myasthenia gravis associated with thyrotoxicosis; (4) periodic paralysis associated with thyrotoxicosis; and (5) muscle hypertrophy and slow muscle contraction and relaxation associated with myxedema and cretinism. Although they are not common, we have encountered up to several examples of these diseases in a single year in our general hospital.