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. Manegold
  • G. F. Hoffmann
  • I. Degen
  • H. Ikonomidou
  • A. Knust
  • M. W. Laaß
  • M. Pritsch
  • E. Wilichowski
  • F. Hörster
Symposium on Neurotransmitter Disorders

DOI: 10.1007/s10545-009-1076-1

Cite this article as:
Manegold, C., Hoffmann, G.F., Degen, I. et al. J Inherit Metab Dis (2009) 32: 371. doi:10.1007/s10545-009-1076-1

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.

Abbreviations

3-OMD

3-ortho-methyldopa

5-HIAA

5-hydroxyindoleacetic acid

5-MTHF

5-methyltetrahydrofolate

AADC

aromatic l-amino acid decarboxylase

CSF

cerebrospinal fluid

HVA

homovanillic acid

MAO

monoamine oxidase

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • C. Manegold
    • 1
  • G. F. Hoffmann
    • 1
  • I. Degen
    • 2
  • H. Ikonomidou
    • 3
  • A. Knust
    • 4
  • M. W. Laaß
    • 5
  • M. Pritsch
    • 4
  • E. Wilichowski
    • 6
  • F. Hörster
    • 1
  1. 1.Division of Inherited Metabolic DiseasesUniversity Children’s HospitalHeidelbergGermany
  2. 2.Department of PediatricsMarienhaus KlinikumNeuwiedGermany
  3. 3.Department of Pediatric NeurologyUniversity of Technology DresdenDresdenGermany
  4. 4.Department of NeuropediatricsDRK-Children’s Hospital SiegenSiegenGermany
  5. 5.Department of PediatricsUniversity of Technology DresdenDresdenGermany
  6. 6.Department of NeuropediatricsUniversity of GöttingenGöttingenGermany