Reduced ornithine catabolism in cultured fibroblasts and phytohaemagglutinin-stimulated lymphocytes from a patient with hyperornithinaemia, hyperammonaemia and homocitrullinuria

The pH of mitochondria of fibroblasts from a hyperornithinaemia, hyperammonaemia, homocitrullinuria‐syndrome patient

“…Up till now 12 patients have been described (Fell et al, 1974;Gatfield et al, 1975;Hommes et aI., 1982Hommes et aI., , 1983Shih et al, 1969). Several groups of investigators have provided evidence that this condition is due to an impairment of the transport ofornithine across the inner mitochondrial membrane (Fell et al, 1974;Gray et al, 1982;Haust et al, 19'81 ;Hommes et al, 1982Hommes et al, , 1983Shih et al, 1980Shih et al, , 1982 but direct proof is lacking.…”

Hyperornithinemia-Hyperammonemia- Homocitrullinuria Syndrome: Low Creatine Excretion and Effect of Citrulline, Arginine, or Ornithine Supplement

“…Several investigators have postulated a specific defect in the transport of ornithine across the inner mitochondrial membrane but a definite proof is still lacking due to controversial results (6,7,(14)(15)(16)(17)(18)(19). Previous reports on therapeutic trials using supplements of ornithine, arginine, lysine or citrulline in patients with HHH syndrome for controlling hyperammonemia and the other metabolic disturbancies (hyperornithinemia, homocitrulline, and orotic acid excretion) led to contradictive results (1, 3, 5-10, 12-15, 19).…”

Ultrastructural changes in fibroblast mitochondria of a patient with HHH‐syndrome

“…Several studies have provided evidence that the basic defect of the HHH-syndrome is expressed in fibroblasts (Shih et al, 1980(Shih et al, , 1982Gray et at., 1982;Hommes et at, 1982). Nevertheless, such dramatic changes in the morphology of mitochondria, as observed in liver mitochondria~ could not be seen in fibroblast mitochondria, except for triangular structures, resembling those seen in liver mitochondria.…”

“…It has been speculated that these unusual membrane structures contribute to the decreased ability of ornithine to reach the matrix space of the mitochondria (Haust et al, 1981). Several studies have indicated that the basic defect of the HHHsyndrome is expressed in fibroblasts (Shih et al, 1980(Shih et al, , 1982Gray et al, 1982;Hommes et al, 1982). The question arises therefore whether such abnormal structures can be demonstrated in fibroblast mitochondria.…”

“…The HHH-syndrome [hyperornithinaemia, hyperammonaemia, homocitrullinuria syndrome (McKusick 23897)], a rare autosomal recessive disease of the urea cycle, is possibly caused by a defective transport of ornithine across the inner mitochondrial membrane (Fell et al, 1974;Shih et al, 1980Shih et al, , 1982Hommes et al, 1982;Gray et at., 1982). Gatfield et at.…”