Defective ornithine metabolism in cultured skin fibroblasts from patients with the syndrome of hyperornithinemia, hyperammonemia and homocitrullinuria.
The syndrome of hyperornithinemia, hyperammonemia, and homocitrullinuria (HHH) is a metabolic disorder resulting in protein intolerance and mental retardation. The primary metabolic defect has yet to be determined. We studied some aspects of ornithine metabolism in cultured skin fibroblasts from two patients from two patients with the HHH syndrome. The fibroblasts failed to incorporate 14C-label from ornithine into protein, a defect also observed in fibroblasts from patients with gyrate atrophy of the choroid and retina and a deficiency of ornithine aminotransferase activity. The defect can be corrected in heterokaryons formed between these two types of fibroblasts. These findings indicate that fibroblasts are suitable for further studying the underlying metabolic defect in HHH syndrome. The combination of the ornithine incorporation assay and genetic complementation analysis provide a confirmatory test for the diagnosis of this syndrome.
D000592:Amino Acid Metabolism, Inborn Errors / Q000378:metabolism*; D000641:Ammonia / Q000097:blood*; D002478:Cells, Cultured; D002956:Citrulline / Q000031:analogs & derivatives* / Q000652:urine; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008956:Models, Chemical; D009952:Ornithine / Q000097:blood*; D011506:Proteins / Q000378:metabolism; D012867:Skin / Q000378:metabolism*
D011506:Proteins; C001352:homocitrulline; D002956:Citrulline; D000641:Ammonia; D009952:Ornithine