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

Journal of Inherited Metabolic Disease volume 32, pages 371–380 (2009)Cite this article

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.

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Fig. 1

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

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Acknowledgement

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.

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Authors and Affiliations

  1. Division of Inherited Metabolic Diseases, University Children’s Hospital, Im Neuenheimer Feld 430, D-69120, Heidelberg, Germany

    C. Manegold, G. F. Hoffmann & F. Hörster

  2. Department of Pediatrics, Marienhaus Klinikum, Neuwied, Germany

    I. Degen

  3. Department of Pediatric Neurology, University of Technology Dresden, Dresden, Germany

    H. Ikonomidou

  4. Department of Neuropediatrics, DRK-Children’s Hospital Siegen, Siegen, Germany

    A. Knust & M. Pritsch

  5. Department of Pediatrics, University of Technology Dresden, Dresden, Germany

    M. W. Laaß

  6. Department of Neuropediatrics, University of Göttingen, Göttingen, Germany

    E. Wilichowski

Authors
  1. C. Manegold
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  2. G. F. Hoffmann
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  3. I. Degen
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  4. H. Ikonomidou
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  5. A. Knust
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  6. M. W. Laaß
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  7. M. Pritsch
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  8. E. Wilichowski
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  9. F. Hörster
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Corresponding author

Correspondence to F. Hörster.

Additional information

Communicating editor: Michael Gibson

Competing interests: None declared

References to electronic databases: Aromatic l-amino acid decarboxylase deficiency: OMIM #608643. Aromatic l-amino acid decarboxylase: EC 4.1.1.28.

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Manegold, C., Hoffmann, G.F., Degen, I. et al. Aromatic l-amino acid decarboxylase deficiency: clinical features, drug therapy and follow-up. J Inherit Metab Dis 32, 371–380 (2009). https://doi.org/10.1007/s10545-009-1076-1

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  • DOI: https://doi.org/10.1007/s10545-009-1076-1

Keywords

  • Levodopa
  • Dystonia
  • Bromocriptine
  • Dopamine Agonist
  • Selegiline