Symposium on Neurotransmitter Disorders

Journal of Inherited Metabolic Disease

, Volume 32, Issue 3, pp 371-380

Aromatic l-amino acid decarboxylase deficiency: clinical features, drug therapy and follow-up

  • C. ManegoldAffiliated withDivision of Inherited Metabolic Diseases, University Children’s Hospital
  • , G. F. HoffmannAffiliated withDivision of Inherited Metabolic Diseases, University Children’s Hospital
  • , I. DegenAffiliated withDepartment of Pediatrics, Marienhaus Klinikum
  • , H. IkonomidouAffiliated withDepartment of Pediatric Neurology, University of Technology Dresden
  • , A. KnustAffiliated withDepartment of Neuropediatrics, DRK-Children’s Hospital Siegen
  • , M. W. LaaßAffiliated withDepartment of Pediatrics, University of Technology Dresden
  • , M. PritschAffiliated withDepartment of Neuropediatrics, DRK-Children’s Hospital Siegen
  • , E. WilichowskiAffiliated withDepartment of Neuropediatrics, University of Göttingen
  • , F. HörsterAffiliated withDivision of Inherited Metabolic Diseases, University Children’s Hospital Email author 

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Summary

Background

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.

Methods

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.

Results

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.

Conclusion

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.