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Long-term follow-up of four patients affected by HHH syndrome.
- Source :
-
Clinica chimica acta; international journal of clinical chemistry [Clin Chim Acta] 2012 Jul 11; Vol. 413 (13-14), pp. 1151-5. Date of Electronic Publication: 2012 Mar 23. - Publication Year :
- 2012
-
Abstract
- 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.<br />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.<br />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.<br />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.<br /> (Copyright © 2012 Elsevier B.V. All rights reserved.)
- Subjects :
- Adult
Amino Acid Transport Systems, Basic genetics
Amino Acids blood
Chromatography, High Pressure Liquid
Chromatography, Ion Exchange
DNA Mutational Analysis
Disease Progression
Female
Follow-Up Studies
Humans
Hyperammonemia blood
Hyperammonemia genetics
Male
Middle Aged
Mitochondrial Membrane Transport Proteins
Ornithine blood
Ornithine deficiency
Ornithine genetics
Phenotype
Time Factors
Urea Cycle Disorders, Inborn blood
Urea Cycle Disorders, Inborn genetics
Hyperammonemia physiopathology
Urea Cycle Disorders, Inborn physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-3492
- Volume :
- 413
- Issue :
- 13-14
- Database :
- MEDLINE
- Journal :
- Clinica chimica acta; international journal of clinical chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 22465082
- Full Text :
- https://doi.org/10.1016/j.cca.2012.03.015