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Approximately 200 patients with defects involving the pyruvate dehydrogenase complex have been described. Most patients have a defect involving the E1-a subunit, and a male predominance is expected because the gene is located on the X chromosome. The neonatal presentation includes hypotonia, episodic apnea, convulsions, weak suck, dysmorphic features, lethargy, low birth weight, failure to thrive, and coma. Continue reading →

Fifty or more pathogenic mtDNA point mutations in tRNA genes have been reported to date. these mutations involve four distinctive clinical conditions that are maternally inherited. These conditions include MELAS, MERRF, a maternally-inherited myopathy and cardiomyopathy (MiMyCa), and a maternally inheritied syndrome of diabetes mellitus and deafness (DAD). Lactic acidosis and RRF commonly accompany these four syndromes.

Two mtDNA-associated clinical syndromes have been described that result from a primary molecular defect involving the nuclear genome. Both conditions are inherited as Mendelian autosomal traits. The first condition is the dominantly-inherited mitochondrial myopathy with multiple deletions of mtDNA. Continue reading →

Succinate dehyrodgenase is a critical step in the Krebs cycle and the first component of complex II in the respiratory chain. Several patients have been described with defects involving complex II presenting with a progressive encephalomyopathy. Continue reading →

Succinate Dehydrogenase

Fumarase Deficiency

Mitochondrial DNA Deletion

Mitochondrial DNA Point Mutation

Pyruvate Dehydrogenase

Mitochondrial defects involving the Krebs cycle (fumarase deficiency, succinate dehydrogenase deficiency) and abnormal coupling of adenosine dephosphate phosphorylation to oxygen uptake (Luft’s diseases) have been described, but the most common mitochondrial myopathies are associated with respiratory chain abnormalities. The clinical Continue reading →

Multiple acyl CoA dehydrogenase deficiency due to impairment of a riboflavin-dependent reaction common to straight and branched-chain acyl CoA molecules commonly is associated with carnitine depletion and a lipid myopathy in which skeletal muscle weakness and fatigability are prominent features. Continue reading →

Primary carnitine deficiency is attributable to impaired cellular carnitine transport and is associated with cardiomyopathy or myopathy. Oral carnitine supplements, L-carnitine 100 mg per kilogram per day in divided doses, may effectively reverse symptoms even when only a modes (but apparently critical) increase in cellular carnitine level can be achieved. Continue reading →

Hepatic and muscle forms of carnitine palmitoyl transferase (CPT) deficiency have been described: the hepatic form is attributable to deficiency of CPT I, the muscle form to deficiency of CPT II. The muscle form of the disease usually becomes symptomatic in the second decade of life or later and is manifested as recurrent muscle fatigue, pain, and myoglobinuria triggered by metabolic challenges such as fasting and prolonged exercise, which normally require fatty acid oxidation as a major source of muscle energy production. Continue reading →