Hyperammonemia is a metabolic condition characterized by elevated levels of ammonia in the blood, and may result in irreversible brain damage if not treated early and thoroughly. Hyperammonemia can be classified into primary or secondary hyperammonemias depending on the underlying pathophysiology. Detoxification of ammonia is mainly accomplished by the urea cycle in periportal hepatocytes. The function of the urea cycle may be affected in a secondary way in a number of different situations. For example, intermediary metabolites that accumulate due to enzymatic defects in other pathways, may inhibit the urea cycle. The most relevant group of disorders in this respect is that of organic acidemias. The urea cycle function may be impaired by substrate deficiencies assumed cause in various disorders including lysinuric protein intolerance, pyrroline-5-carboxylate synthetase deficiency, and fatty acid oxidation defects. In addition to the urea cycle, mammals require the function of glutamine synthetase to completely detoxify ammonia.
Autosomal recessive cutis laxa type IIIA (ARCL3A) [DS:H00557] is caused by homozygous or compound heterozygous mutation in the ALDH18A1 gene, and its clinical features include hyperammonemia.
Baumgartner MR, Hu CA, Almashanu S, Steel G, Obie C, Aral B, Rabier D, Kamoun P, Saudubray JM, Valle D
タイトル
Hyperammonemia with reduced ornithine, citrulline, arginine and proline: a new inborn error caused by a mutation in the gene encoding delta(1)-pyrroline-5-carboxylate synthase.
