Pathobiochemical implications of hyperdopaminuria in patients with aromatic L-amino acid decarboxylase deficiency
| Autor: | Georg F. Hoffmann, Ron A. Wevers, A. H. van Gennip, Agata Fiumara, Jaak Jaeken, N. G. G. M. Abeling, A. Knust, C. Brautigam, Peter G. Barth |
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| Přispěvatelé: | Other departments |
| Rok vydání: | 2000 |
| Předmět: |
medicine.medical_specialty
Dopamine Inborn errors of metabolism Biology Serotonergic Levodopa chemistry.chemical_compound Internal medicine Monoaminergic Genetics medicine Humans Erfelijke stofwisselingsziekten Neurotransmitter Genetics (clinical) Inherited neurotransmitten diseases Aromatic L-amino acid decarboxylase Homovanillic Acid Erfelijke ziekten in de neurotransmissie medicine.anatomical_structure Endocrinology chemistry Aromatic-L-Amino-Acid Decarboxylases 3 4-Dihydroxyphenylacetic Acid Catecholaminergic cell groups Serotonin Adrenal medulla medicine.drug |
| Zdroj: | Journal of Inherited Metabolic Disease, 23, 325-328 Journal of inherited metabolic disease, 23(4), 325-328. Springer Netherlands Journal of Inherited Metabolic Disease, 23, pp. 325-328 |
| ISSN: | 0141-8955 |
| Popis: | Aromatic L-amino acid decarboxylase (AADC, EC 4.1.1.28) catalyses the conversion of 5-hydroxytryptophan to serotonin in serotonergic neurons and of dopa to dopamine in catecholaminergic neurons and adrenal medullary cells. The enzyme thus plays a key role in the synthesis of both groups of neurotransmitter biogenic amines. AADC is found in both neuronal (monoaminergic neurons in the CNS, adrenal medulla) and nonneuronal cells (liver, intestine, kidney), which distribution is ascribed to tissue-specific expression of the AADC gene as a result of alternative promoter usage and differential splicing (Jahng et al 1996). The first human case of AADC deficiency was described (Hyland and Clayton 1990; Hyland et al 1992) in 1990, and since then several new patients have been identified (Abeling et al 1998; Fiumara et al 1998; Hyland et al 1998; Korenke et al 1997; Maller et al 1997). Mutations in the human AADC gene have been described in six patients, but expression studies to prove their association with altered enzyme activity are still in progress (Chang et al 1998). The condition is considered to be a neurotransmitter defect leading to a combined deficiency of the catecholamines and serotonin. The clinical presentation comprises developmental delay, hypotonia and an extrapyramidal movement disorder with oculogyric crises. Temperature instability, sweating and hypersalivation are also observed. Most patients present in the first years of life. The diagnosis is based on abnormal metabolite patterns in CSF, plasma and urine and on greatly reduced activity of AADC in plasma. Recently (Abeling et al 1998) a new case of AADC deficiency in a 2-year-old Dutch girl was published, with mild clinical presentation and unexpected biochemical findings, i.e. a urinary metabolite pattern partly consistent with AADC deficiency, but also with elements that could not easily be explained from the defect. The most prominent finding was hyperdopaminuria. In addition, elevated urinary concentrations of dopamine metabolites were found. This prompted us to perform further investigations in this and other AADC-deficient patients in search of an explanation for this finding. |
| Databáze: | OpenAIRE |
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