Document Detail

Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome with stroke-like imaging presentation: clinical, biochemical and molecular analysis.
MedLine Citation:
PMID:  17825324     Owner:  NLM     Status:  MEDLINE    
Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is an autosomal recessive disorder caused by mutations in ORNT1 gene that encodes a mitochondrial ornithine transporter. It has variable clinical presentations with episodic hyperammonemia, liver dysfunction, and chronic neurological manifestations. In this work, we report the findings of HHH syndrome in 3 Saudi siblings. The 4-year-old proband presented with recurrent Reye-like episodes, hypotonia, and multiple stroke-like lesions on brain MRI. Biochemical and molecular analysis confirmed that she had HHH syndrome. She significantly improved on protein restriction and sodium benzoate. Her two older siblings have milder phenotypes with protein intolerance and learning problems. In comparison to their sister, their homocitrulline and orotic acid were only mildly elevated even before treatment. The three patients were homozygous for a novel mutation in ORNT1 with a Gly220Arg change. In view of the CNS lesions, which initially were felt to be suggestive of MELAS, we sequenced the entire mtDNA genome and no potential pathogenic mutations were detected. Analysis of ORNT2 did not provide explanation of the clinical and biochemical variability. This work presents a yet unreported CNS involvement pattern, notably multiple supratentorial stroke-like lesions in association with HHH syndrome. Moreover, it illustrates considerable clinical/biochemical correlation, and describes a novel mutation. We suggest including HHH syndrome in the differential diagnosis of patients found to have stroke-like lesions on brain MRI.
Zuhair N Al-Hassnan; Mohamed S Rashed; Osama Y Al-Dirbashi; Zoltan Patay; Zuhair Rahbeeni; Khaled K Abu-Amero
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Publication Detail:
Type:  Case Reports; Journal Article     Date:  2007-09-07
Journal Detail:
Title:  Journal of the neurological sciences     Volume:  264     ISSN:  0022-510X     ISO Abbreviation:  J. Neurol. Sci.     Publication Date:  2008 Jan 
Date Detail:
Created Date:  2007-12-07     Completed Date:  2008-04-08     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0375403     Medline TA:  J Neurol Sci     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  187-94     Citation Subset:  IM    
Department of Medical Genetics, King Faisal Specialist Hospital & Research Centre, Riyadh 11211, Saudi Arabia.
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MeSH Terms
Amino Acid Metabolism, Inborn Errors / genetics*,  metabolism,  physiopathology*
Amino Acid Transport Systems, Basic / genetics*
Brain / metabolism,  pathology,  physiopathology
Brain Diseases, Metabolic, Inborn / genetics*,  metabolism,  physiopathology*
Child, Preschool
Citrulline / analogs & derivatives,  metabolism
DNA Mutational Analysis
Food, Formulated
Genetic Markers / genetics
Genetic Predisposition to Disease / genetics*
Genetic Testing
Hyperammonemia / genetics,  metabolism,  physiopathology
Magnetic Resonance Imaging
Mutation / genetics
Ornithine / metabolism
Saudi Arabia
Sodium Benzoate / therapeutic use
Stroke / genetics,  pathology,  physiopathology
Reg. No./Substance:
0/Amino Acid Transport Systems, Basic; 0/Genetic Markers; 0/SLC25A15 protein, human; 1190-49-4/homocitrulline; 372-75-8/Citrulline; 532-32-1/Sodium Benzoate; 7006-33-9/Ornithine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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