Episodic hyperammonemia in adult siblings with hyperornithinemia, hyperammonemia, and homocitrullinuria syndrome
M. Tuchman, D. S. Knopman and V. E. Shih
Department of Pediatrics, University of Minnesota, Minneapolis 55455.
A 39-year-old man and his 42-year-old sister, both vegetarians, had
episodic confusion for many years, but their mental function was normal
between those episodes. They were recently diagnosed with
hyperornithinemia, hyperammonemia, and homocitrullinuria syndrome.
Hyperammonemia was documented during an episode of confusion in the male
sibling but not in his sister. Both had elevated plasma ornithine,
glutamine, and alanine levels and persistently low plasma lysine levels.
Homocitrulline was present in their urine, and orotic aciduria and
orotidinuria developed in the male sibling following ingestion of
allopurinol. Studies on their cultured skin fibroblasts showed deficient
metabolism of ornithine, indicating a defect in ornithine transport across
the mitochondrial membrane. During therapy with citrulline and
phenylbutyrate sodium, plasma ornithine levels increased in both patients,
while plasma levels of glutamine and alanine decreased to normal. Since
therapy started, their clinical conditions have also improved, and no
recurrent neurologic dysfunction has occurred during a follow-up period of
20 months.
