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Hyperornithinemia, hyperammonemia, and homocitrullinuria associated with decreased carbamyl phosphate synthetase I

P D Gatfield, E Taller, D M Wolfe

    Pediatric Research
    |May 1, 1975
    PubMed

    Insights

    This study identifies a urea cycle disorder causing hyperornithinemia, homocitrullinuria, and hyperammonemia. The defect, likely autosomal recessive, involves impaired ornithine transport into mitochondria, impacting urea cycle and lysine metabolism.

    Area of Science:

    • Biochemistry
    • Genetics
    • Pediatrics

    Background:

    • Hyperornithinemia, homocitrullinuria, and hyperammonemia are rare metabolic disorders.
    • These conditions are often associated with defects in the urea cycle or related metabolic pathways.
    • Understanding the underlying mechanisms is crucial for diagnosis and management.

    Purpose of the Study:

    • To describe six subjects with a combined presentation of hyperornithinemia, homocitrullinuria, and hyperammonemia.
    • To investigate the enzymatic and genetic basis of this disorder.
    • To explore the relationship between lysine metabolism and the urea cycle in affected individuals.

    Main Methods:

    • Enzymatic assays on liver biopsy and leukocytes.
    • Ornithine, citrulline, lysine, and homocitrulline loading studies.
    • Analysis of liver fine structure using electron microscopy.
    • Clinical assessment and dietary management evaluation.

    Main Results:

    • Enzymatic assays revealed decreased carbamoyl phosphate synthetase I (CPS I) activity, indicating a defect early in the urea cycle.
    • Loading studies confirmed a block between ornithine and citrulline, consistent with enzymatic findings.
    • Excessive homocitrulline biosynthesis was observed, linked to lysine intake but not a block in lysine catabolism.
    • Dietary protein restriction was necessary for younger patients to control hyperammonemia.
    • Electron microscopy showed abnormal liver mitochondria with a peculiar periodic structure near the inner membrane.

    Conclusions:

    • The disorder is characterized by a defect in the urea cycle, likely involving impaired ornithine transport into mitochondria.
    • The findings suggest a link between lysine metabolism and the urea cycle, though the precise mechanisms require further elucidation.
    • The inheritance pattern appears to be autosomal recessive.
    • Management involves dietary protein restriction, particularly in younger, more severely affected individuals.

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