A novel mutation, P126R, in a Japanese patient with HHH syndrome

Pediatr Neurol. 2002 Jan;26(1):65-7. doi: 10.1016/s0887-8994(01)00335-6.


Mitochondrial ornithine transporter deficiency, or HHH syndrome, is a metabolic disorder resulting in various neurologic symptoms, including mental retardation, spastic paraparesis with pyramidal signs, cerebellar ataxia, and episodic disturbance of consciousness or coma caused by hyperammonemia. Several mutations have been reported in the ORNT1 gene encoding mitochondrial ornithine transporter of patients with this disorder. In this article, we report a new patient, a male 15 years of age, who had typical clinical features of HHH syndrome. Because the patient did not have any of the three mutations previously described in other Japanese patients with HHH syndrome, and the only material available from the patient was peripheral leukocytes, we established a genomic polymerase chain reaction method using intronic primers to amplify every exon of the ORNT1 gene, and we directly sequenced the polymerase chain reaction products. Using this method, we documented a novel mutation in this patient, P126R, and demonstrated that HHH syndrome is genetically heterogeneous, even in the Japanese population.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Ammonia / blood
  • Base Sequence
  • Brain Diseases / diagnostic imaging
  • Brain Diseases / pathology
  • Carrier Proteins / genetics
  • Cysts / diagnostic imaging
  • Cysts / pathology
  • DNA Primers
  • Exons
  • Gene Expression / genetics*
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Metabolism, Inborn Errors / genetics*
  • Metabolism, Inborn Errors / metabolism*
  • Methionine / urine
  • Mitochondrial Diseases / genetics*
  • Mitochondrial Diseases / metabolism*
  • Molecular Sequence Data
  • Ornithine / deficiency*
  • Ornithine / genetics*
  • Point Mutation / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Septum Pellucidum / pathology
  • Syndrome
  • Tomography, X-Ray Computed


  • Carrier Proteins
  • DNA Primers
  • Ammonia
  • Methionine
  • Ornithine