Aromatic l-amino acid decarboxylase deficiency: clinical features, drug therapy and follow-up
Aromatic l-amino acid decarboxylase (AADC) deficiency is a disorder of biogenic amine metabolism resulting in generalized combined deficiency of serotonin, dopamine and catecholamines. Main clinical features are developmental delay, muscular hypotonia, dystonia, oculogyric crises and additional extraneurological symptoms. Response to therapy has been variable and unsatisfactory; the overall prognosis is guarded.
To gain more insight into this rare disorder we collected clinical and laboratory data of nine German patients. All patients were clinically examined by one investigator, and their responses to different drug regimes were evaluated by the patients’ charts.
Symptoms were obvious from early infancy. Later, main neurological features were truncal muscular hypotonia, hypokinesia, oculogyric crises and rigor. Three patients had single seizures. All patients presented distinct extraneurological symptoms, such as hypersalivation, hyperhidrosis, nasal congestion, sleep disturbances and hypoglycaemia. In CSF all patients revealed the pattern typical of AADC with decreased concentrations of homovanillic and 5-hydroxyindoleacetic acid and elevated concentration of 3-ortho-methyldopa. Diagnosis was confirmed by measurement of AADC activity in plasma in all patients. Drug regimes consisted of vitamin B6, dopamine agonists, MAO inhibitors and anticholinergics in different combinations. No patient achieved a complete recovery from neurological symptoms, but partial improvement of mobility and mood could be achieved in some.
AADC deficiency is a severe neurometabolic disorder, characterized by muscular hypotonia, dystonia, oculogyric crises and additional extraneurological symptoms. Medical treatment is challenging, but a systematic trial of the different drugs is worthwhile.
KeywordsLevodopa Dystonia Bromocriptine Dopamine Agonist Selegiline
aromatic l-amino acid decarboxylase
The authors thank Professor Keith Hyland (Horizon Molecular Medicine, Atlanta, GA, USA) and Dr Rüdiger Kläs and Dr Friedrich W. Cremer (Zentrum für Humangenetik, Mannheim, Germany) for performing molecular genetic investigations of the AADC gene.
- Abeling NG, van Gennip AH, Barth PG, van Cruchten A, Westra M, Wijburg FA (1998) Aromatic l-amino acid decarboxylase deficiency: a new case with a mild clinical presentation and unexpected laboratory findings. J Inherit Metab Dis 21: 240–242. doi: 10.1023/A:1005307919767.PubMedCrossRefGoogle Scholar
- Ito S, Nakayama T, Die S, etal (2008) Aromatic l-amino acid decarboxylase deficiency associated with epilepsy mimicking non-epileptic involuntary movements. Dev Med Child Neurol 50(11): 876–878.Google Scholar
- Korenke GC, Christen HJ, Hyland K, Hunnemann D, Hanefeld F (1997) Aromatic l-amino acid decarboxylase deficiency: an extrapyramidal movement disorder with oculogyric crisis. Eur J Pediatr Neurol 1: 67–71.Google Scholar
- Lee HF, Tsai CR, Chi CS, Chang TM, Lee HJ (2008) Aromatic l-amino acid decarboxylase deficiency in Taiwan. Eur J Paediatr Neurol. Jun 20. [Epub ahead of print].Google Scholar