Clinical case of a patient with AADC deficiency of L-aromatic amino acid decarboxylase: diagnostic route and therapeutic options

L-aromatic amino acid decarboxylase deficiency (AADC) is a rare autosomal recessive neurometabolic disease characterized by impaired biosynthesis of neurotransmitters and manifested by disorders of movement and autonomic regulation.In the article there is discussed the diagnostic path and treatment options for a 7-year patient with severe AADC deficiency. Combination of severe neurological disorders (muscular hypotension, dystonia, hyperkinesis, oculogyric crises) and autonomic disorders (increased sweating, hypersalivation, thermoregulation disorders, nasal congestion, dyspepsia, etc.) is clearly demonstrated to require the detection of 3-O-methyldopa in dried blood spots to exclude AADC deficiency. Given the emergence of gene therapy, which is available to patients with a confirmed diagnosis of AADC deficiency in Russia within the criteria of the Circle of Kindness Foundation, it is necessary to popularize information about L-aromatic amino acid decarboxylase deficiency in the general medical community, to improve the prognosis and quality of life in AADC patients.

Contribution:
Uvakina E.V. — concept and design of the study, writing the text, editing;
Kuzenkova L.M. — concept and design of the study, writing the text, editing;
Gukosyan D.I. — concept and design of the study, writing the text, editing;
Popovich S.G. — editing;
Podkletnova T.V. — editing;
Lyalina A.A. — editing;
Pushkov A.A. — editing;
Savostyanov K.V. — editing;
Kurova Y.A. — editing;
Nikolenko D.S. — editing.
All co-authors are responsible for the integrity of all parts of the manuscript and approval of its final version.

Acknowledgements. The study had no sponsorship.

Conflict of interest. The authors declare no conflict of interest.

Received: December 17, 2024
Accepted: January 10, 2025
Published: January 31, 2025

1. Buesch K., Zhang R., Szczepańska K., Veličković V., Turner L., Despotović M., et al. Burden and severity of disease of aromatic L-amino acid decarboxylase deficiency: a systematic literature review. Curr. Med. Res. Opin. 2022; 38(11): 1871–82. https://doi.org/10.1080/03007995.2022.2072090

2. Himmelreich N., Montioli R., Garbade S.F., Kopesky J., Elsea S.H., Carducci C., et al. Spectrum of DDC variants causing aromatic l-amino acid decarboxylase (AADC) deficiency and pathogenicity interpretation using ACMG-AMP/ACGS recommendations. Mol. Genet. Metab. 2022; 137(4): 359–81. https://doi.org/10.1016/j.ymgme.2022.11.003

3. Himmelreich N., Bertoldi M., Alfadhel M., Alghamdi M.A., Anikster Y., Bao X., et al. Prevalence of DDC genotypes in patients with aromatic L-amino acid decarboxylase (AADC) deficiency and in silico prediction of structural protein changes. Mol. Genet. Metab. 2023; 139(3): 107624. https://doi.org/10.1016/j.ymgme.2023.107624

4. Wassenberg T., Molero-Luis M., Jeltsch K., Hoffmann G.F., Assmann B., Blau N., et al. Consensus guideline for the diagnosis and treatment of aromatic l-amino acid decarboxylase (AADC) deficiency. Orphanet J. Rare Dis. 2017; 12(1): 12. https://doi.org/10.1186/s13023-016-0522-z

5. Civallero G., Kubaski F., Pereira D., Rübensam G., Herbst Z.M., Silva C., et al. Corrigendum to “Biochemical diagnosis of aromatic-L-amino acid decarboxylase deficiency (AADCD) by assay of AADC activity in plasma using liquid chromatography/tandem mass spectrometry” [32/100888 (2022) page 1-4]. Mol. Genet. Metab. Rep. 2022; 34: 100945. https://doi.org/10.1016/j.ymgmr.2022.100945

6. Hwu W.L., Hsu R.H., Li M.H., Lee H.M., Chen H.A., Lee N.C., et al. Aromatic l-amino acid decarboxylase deficiency in Taiwan. JIMD Rep. 2023; 64(5): 387–92. https://doi.org/10.1002/jmd2.12387

7. Hyland K., Clayton P.T. Aromatic amino acid decarboxylase deficiency in twins. J. Inherit. Metab. Dis. 1990; 13(3): 301–4. https://doi.org/10.1007/bf01799380

8. Himmelreich N., Montioli R., Bertoldi M., Carducci C., Leuzzi V., Gemperle C., et al. Aromatic amino acid decarboxylase deficiency: Molecular and metabolic basis and therapeutic outlook. Mol. Genet. Metab. 2019; 127(1): 12–22. https://doi.org/10.1016/j.ymgme.2019.03.009

9. Pearson T.S., Gilbert L., Opladen T., Garcia-Cazorla A., Mastrangelo M., Leuzzi V., et al. AADC deficiency from infancy to adulthood: Symptoms and developmental outcome in an international cohort of 63 patients. J. Inherit. Metab. Dis. 2020; 43(5): 1121–30. https://doi.org/10.1002/jimd.12247

10. Whitehead N., Schu M., Erickson S.W., Croxford J., Peters M., Hyland K. Estimated prevalence of aromatic l-amino acid decarboxylase (AADC) deficiency in the United States, European Union, and Japan [poster]. In: Annual Congress of the European Society for Gene and Cell Therapy. Lausanne; 2018.

11. Pons R., Ford B., Chiriboga C.A., Clayton P.T., Hinton V., Hyland K., et al. Aromatic L-amino acid decarboxylase deficiency: clinical features, treatment, and prognosis. Neurology. 2004; 62(7): 1058–65. https://doi.org/10.1212/wnl.62.7.1058

12. Brun L., Ngu L.H., Keng W.T., Ch’ng G.S., Choy Y.S., Hwu W.L., et al. Clinical and biochemical features of aromatic L-amino acid decarboxylase deficiency. Neurology. 2010; 75(1): 64–71. https://doi.org/10.1212/wnl.0b013e3181e620ae

13. The Circle of Goodness Foundation. Categories of children who are indicated for the administration of the drug Eladokagen exuparvec. Available at: https://фондкругдобра.рф/экспертный-совет-№37-от-02-05-2024/ (in Russian)