Case Report

JIMD Reports - Case and Research Reports, 2011/3

Volume 3 of the series JIMD Reports pp 97-102

Date:

Adult-Onset Presentation of a Hyperornithinemia-Hyperammonemia-Homocitrullinuria Patient Without Prior History of Neurological Complications

  • Kamer TezcanAffiliated withDepartment of Genetics, Kaiser Permanente
  • , Kristal T. LouieAffiliated withDepartment of Genetics, Kaiser Permanente
  • , Yong QuAffiliated withDepartment of Genetic Testing, Kaiser Permanente
  • , Jorge VelasquezAffiliated withDepartment of Pediatrics, University of California-Irvine
  • , Frank ZaldivarAffiliated withDepartment of Pediatrics, University of California-Irvine
  • , Natalia Rioseco-CamachoAffiliated withDepartment of Pediatrics, University of California-Irvine
  • , José Angel CamachoAffiliated withDepartment of Pediatrics, University of California-Irvine Email author 

* Final gross prices may vary according to local VAT.

Get Access

Abstract

The Hyperornithinemia-Hyperammonemia-Homocitrullinuria (HHH) syndrome is a disorder of the urea cycle and ornithine degradation pathway caused by mutations in the mitochondrial ornithine transporter, ORNT1 (SLC25A15). In general, the majority of patients with HHH syndrome come to medical attention during infancy or early school years with symptoms such as learning disabilities, changes in cognitive development, spasticity, or liver dysfunction. In this report, we describe a 35-year-old male of Indian descent who was diagnosed with HHH syndrome after he presented to the emergency room with gastroenteritis, disorientation, and slurred speech. Molecular analysis revealed that this patient was heterozygous for two ORNT1 mutations, p.[Gly220Arg(+)Arg275X] (c.[658G>A(+)823C>T]) that had been previously reported in homozygous probands who presented during the first year of life. Cellular studies revealed that the ORNT1 p.Gly220Arg mutation was nonfunctional but targeted to the mitochondria. Given that this patient was a successful college graduate on a vegetarian diet without a prior history of learning or neurological impairment, additional factors such as gene redundancy, environmental, and epigenetic factors may have contributed to the delay in onset of presentation and lack of any previous symptoms. To the best of our knowledge, this is the first reported case of an adult-onset HHH syndrome presentation without a prior history of neurological or cognitive deficiency.