Reversible Leukoencephalopathy in a Man with Childhood-onset Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome

Intern Med. 2022 Feb 15;61(4):553-557. doi: 10.2169/internalmedicine.7843-21. Epub 2021 Aug 24.

Abstract

A 49-year-old Japanese man had shown developmental delay, learning difficulties, epilepsy, and slowly progressive gait disturbance in elementary school. At 46 years old, he experienced repeated drowsiness with or without generalized convulsions, and hyperammonemia was detected. Brain magnetic resonance imaging detected multiple cerebral white matter lesions. An electroencephalogram showed diffuse slow basic activities with 2- to 3-Hz δ waves. Genetic tests confirmed a diagnosis of hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome. Leukoencephalopathy was resolved following the administration of L-arginine and lactulose with a decrease in plasma ammonia levels and glutamine-glutamate peak on magnetic resonance spectroscopy. Leukoencephalopathy in HHH syndrome may be reversible with the resolution of hyperammonemia-induced glutamine toxicity.

Keywords: HHH syndrome; MRS; glutamine toxicity; hyperammonemia; leukoencephalopathy; magnetic resonance spectroscopy.

Publication types

  • Case Reports

MeSH terms

  • Ammonia
  • Child
  • Humans
  • Hyperammonemia* / diagnosis
  • Hyperammonemia* / genetics
  • Leukoencephalopathies*
  • Male
  • Middle Aged
  • Ornithine / deficiency
  • Urea Cycle Disorders, Inborn* / complications
  • Urea Cycle Disorders, Inborn* / diagnosis
  • Urea Cycle Disorders, Inborn* / genetics

Substances

  • Ammonia
  • Ornithine

Supplementary concepts

  • HHH syndrome