Respiratory chain disorders deficiency

Defects of complex II. These have not been fully characterized in the few reported patients, and the diagnosis has often been based solely on a decrease of succinate-cytochrome c reductase activity (Fig. 42-3). However, partial complex II deficiency was documented in muscle and cultured fibroblasts from two sisters with clinical and neuroradiological evidence of Leigh s syndrome, and molecular genetic analysis showed that both patients were homozygous for a point mutation in the flavoprotein subunit of the complex [17]. This was the first documentation of a molecular defect in the nuclear genome associated with a respiratory chain disorder. 

Several classes of inborn errors of metabolism in addition to inborn errors of urea synthesis can cause neonatal hyperammonemia. These include organic acidurias, fatty acid oxidation defects, amino acidopathies, and mitochondrial respiratory chain disorders. All of these disorders have a number of features in common. Labor and delivery tend to be normal, and there are no predisposing risk factors. Clinical features present after 24 h of life and are progressive. They are inherited, and thus a family history of previously affected children or neonatal deaths may be present. While most are inherited in an autosomally recessive manner, ornithine tran-scarbamoylase (OTC) deficiency is X linked, and a family history of affected males in the maternal pedigree is not uncommon. 

Muscle hypotonia is a trait demonstrated by many children bom with an inherited metabolic disease. Floppy baby syndrome, typical for such disorders as Prader-Willi syndrome and severe motor neuron diseases, may be also present in inborn lactic acidosis, some respiratory chain disorders, nonketotic hyperglycemia, molybdenum cofactor deficiency, sulfite oxidase deficiency, peroxisomal disorders, glycosylation disorders, and Pompe disease [1,2]. 

All disorders except those in group 5 are due to defects of nDNA and are transmitted by Mendelian inheritance. Disorders of the respiratory chain can be due to defects of nDNA or mtDNA. Usually, mutations of nDNA cause isolated, severe defects of individual respiratory complexes, whereas mutations in mtDNA or defects of intergenomic communication cause variably severe, multiple deficiencies of respiratory chain complexes. The description that follows is based on the biochemical classification. 

Hypertrophic cardiomyopathy, a thick, rigid cardiac muscle, is also seen in inborn errors, with some overlap with disorders associated with a dilated phenotype. This includes carnitine deficiency, primary respiratory chain defects, Barth syndrome, several glycogenoses (e.g., GSD III, rv, and IX), and lysosomal storage disorders. In lysosomal storage disease the valves are typically more affected than the muscle itself. In the neonate there should be high suspicion for GSD type... 

Amino acid determination in blood and urine may be helpful. Alanine is increased in many patients with a mitochondrial disorder (see above). Deficiency of E3 complex leads to branched-chain amino acid elevation. Severe generalised amino aciduria associated with DeToni-Fanconi-Debrd tubulopathy may indicate a respiratory chain defect. 

The answer is a. (Murray, pp 627-661. Scriver, pp 3897-3964. Sack, pp 121-138. Wilson, pp 287-320.) Vitamins A, D, E, and K are all fat-soluble. The physical characteristics of fat-soluble vitamins derive from the hydrophobic nature of the aliphatic chains composing them. The other vitamins listed are water-soluble, efficiently administered orally, and rapidly absorbed from the intestine. Fat-soluble vitamins must be administered intramuscularly or as oral emulsions (mixtures of oil and water). In intestinal disorders such as chronic diarrhea or malabsorption due to deficient digestive enzymes, fat-soluble vitamins are poorly absorbed and can become deficient. Supplementation of fat-soluble vitamins is thus routine in disorders like cystic fibrosis (219700), a cause of respiratory and intestinal disease that is the likely diagnosis in this child. 

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