Journal of Inherited Metabolic Disease

, Volume 32, Issue 3, pp 371–380 | Cite as

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

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

References

  1. Abdenur JE, Abeling NG, Specola N, etal (2006) Aromatic l-amino acid decarboxylase deficiency: unusual neonatal presentation and additional findings in organic acid analysis. Mol Gen Metab 87: 48–53. doi:10.1016/j.ymgme.2005.09.007.CrossRefGoogle Scholar
  2. 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
  3. Anselm IA, Darras BT (2006) Catecholamine toxicity in aromatic l-amino acid decarboxylase deficiency. Pediatr Neurol 35(2): 142–144. doi:10.1016/j.pediatrneurol.2006.01.008.PubMedCrossRefGoogle Scholar
  4. Brautigam C, Wevers R, Hyland K, etal (2000) The influence of l-dopa on methylation capacity in aromatic l-amino acid decarboxylase deficiency. J Inherit Metab Dis 23: 321–324. doi:10.1023/A:1005698223186.PubMedCrossRefGoogle Scholar
  5. Brautigam C, Hyland K, Wevers R, etal (2002) Clinical and laboratory findings in twins with neonatal epileptic encephalopathy mimicking aromatic l-amino acid decarboxylase deficiency. Neuropediatrics 33: 113–117. doi:10.1055/s-2002-33673.PubMedCrossRefGoogle Scholar
  6. Burlina AB, Burlina AP, Hyland K, Bonafe L, Blau N (2001) Autistic syndrome and aromatic l-aminoacid decarboxylase deficiency. J Inherit Metab Dis 24(Supplement 1): 34. doi:10.1023/A:1012471928628.Google Scholar
  7. Chang YT, Mues G, McPherson JD, etal (1998) Mutations in the human aromatic l-amino acid decarboxylase gene. JInherit Metab Dis 21: 4. doi:10.1023/A:1005467830063.CrossRefGoogle Scholar
  8. Chang YT, Radhakant S, Marsh JL, etal (2004) Levodopa-responsive aromatic l-amino acid decarboxylase deficiency. Ann Neurol 55: 435–438. doi:10.1002/ana.20055.PubMedCrossRefGoogle Scholar
  9. Fiumara A, Bräutigam C, Hyland K (2002) Aromatic l-amino acid decarboxylase deficiency with hyperdopaminuria. Clinical and laboratory findings in response to different therapies. Neuropediatrics 33: 203–208. doi:10.1055/s-2002-34497.PubMedCrossRefGoogle Scholar
  10. Hyland K, Clayton PT (1990) Aromatic amino acid decarboxylase deficiency in twins. J Inherit Metab Dis 13: 301–304. doi:10.1007/BF01799380.PubMedCrossRefGoogle Scholar
  11. Hyland K, Clayton PT (1992) Aromatic l-amino acid decarboxylase deficiency: diagnostic methodology. Clin Chem 38: 2405–2410.PubMedGoogle Scholar
  12. Hyland K, Surtees RAH, Rodeck C, Clayton PT (1992) Aromatic l-amino acid decarboxylase: deficiency: clinical features, diagnosis and treatment of a new inborn error of neurotransmitter amine synthesis. Neurology 42: 1980–1988.PubMedGoogle Scholar
  13. 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
  14. 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
  15. 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
  16. Malller A, Hyland K, Milstien S, Biaggioni I, Butler IJ (1997) Aromatic l-amino acid decarboxylase deficiency: clinical features, diagnosis and treatment of a second family. J Child Neurol 12: 349–354.PubMedCrossRefGoogle Scholar
  17. Mills PB, Surtees RA, Champion MP, etal (2005) Neonatal epileptic encephalopathy caused by mutations in the PNPO gene encoding pyridox(am)ine 5′-phosphate oxidase. Hum Mol Genet 14: 1077–1086.PubMedCrossRefGoogle Scholar
  18. Pons R, Ford B, Chiriboga CA, etal (2004) Aromatic l-amino acid decarboxylase deficiency: clinical features, treatment and prognosis. Neurology 62: 1058–1065.PubMedGoogle Scholar
  19. Swoboda KJ, Hyland K, Goldstein DS, etal (1999) Clinical and therapeutic observations in aromatic l-amino acid decarboxylase deficiency. Neurology 53: 1205–1211.PubMedGoogle Scholar
  20. Swoboda KJ, Saul JP, McKenna C, Speller NB, Hyland K (2003) Aromatic l-amino acid decarboxylase deficiency: overview of clinical features and outcome. Ann Neurol 54(Supplement 6): 49–55.CrossRefGoogle Scholar
  21. Tay SK, Poh KS, Hyland K, etal (2007) Unusually mild phenotype of AADC deficiency in 2 siblings. Mol Genet Metab 91(4): 374–378.PubMedCrossRefGoogle Scholar

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

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