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Long-term follow-up of four patients affected by HHH syndrome.
MedLine Citation:
PMID:  22465082     Owner:  NLM     Status:  Publisher    
BACKGROUND: In hyperornithinemia-hyperammonemia-homocitrullinemia (HHH) syndrome, impaired ornithine transport across the mitochondrial membrane causes ornithine accumulation in cytoplasm. The resulting mitochondrial ornithine deficiency leads to reduced clearance of ammonia through the urea cycle. First described in 1969, no long-term follow-up has been reported. METHODS: Four patients were followed up for 11 to 38y. Diagnosis was made by plasma amino acid analysis using ion exchange chromatography, HPLC orotic acid measurement, and (14)C-ornithine incorporation study using cultured fibroblasts. DNA from fibroblasts was amplified and sequenced. Blood ammonia was controlled by restriction of protein intake. RESULTS: All patients had reduced (14)C-ornithine incorporation. Mutation analysis revealed two novel mutations in the ORNT1 gene. Neurologic outcome included memory loss, low IQ, tremor, spasticity of extremities, bladder incontinence, and abnormal gait. Neuroimaging revealed subcortical, cerebral and cerebellar atrophy, sparing the basal ganglia. Individual examination showed pyramidal signs, cerebellar signs, paraplegia, movement disorder, dystonia, and epilepsy. One patient had 3 pregnancies, one of which resulted in intrauterine growth retardation. CONCLUSIONS: Our patients expand the clinical phenotype of adults with HHH. Long-term follow-up showed serious neurologic outcomes in all patients; three patients clearly exhibited progression of neurologic dysfunction despite control of hyperammonemia. Intracellular ornithine deficiency may adversely affect brain functions.
Sook Z Kim; Wung J Song; William L Nyhan; Can Ficicioglu; Roseann Mandell; Vivian E Shih
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-3-23
Journal Detail:
Title:  Clinica chimica acta; international journal of clinical chemistry     Volume:  -     ISSN:  1873-3492     ISO Abbreviation:  -     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-4-2     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1302422     Medline TA:  Clin Chim Acta     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier B.V.
Korea Genetic Research Center, Cheong Ju, Republic of Korea.
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