Dados do Trabalho

Título

CASE REPORT OF AROMATIC L-AMINO ACID DECARBOXYLASE (AADC) DEFICIENCY CONFIRMED BY ENZYMATIC TEST

Apresentação do caso único

2 years and 8 months old male subject, referred to the neurogenetics clinic in September 2023 due to neurodevelopmental delay, hypotonia and oculogyric crises. Born term from vaginal birth, without complications, at gestational age of 41 weeks, with positive history of parental consanguinity. At the age of 5 months, the patient had not developed head support, and by the same age started oculogyric crises associated with episodes of intense sweating. Initial workup included karyotype, CGH array, brain MRI and electroencephalogram, which showed no abnormalities. Exome showed one pathogenic variant and one variant of unknown significance (VUS) of the DDC gene, both in heterozygous, and a variant of the HECTD4 gene, also in heterozygous, classified as probably pathogenic. Despite the presence of a VUS in the exome, due to the suggestive clinical features, and enzymatic workup with activity of Aromatic L-Amino Acid Decarboxylase quantification was performed, showing a result of 0 nmol/L/min, confirming the AADC deficiency.

Discussão

Aromatic L-amino acid decarboxylase is the final enzyme in the biosynthesis of the monoamine neurotransmitters serotonin and dopamine, and dopamine is the precursor for norepinephrine and epinephrine. AADC deficiency is a rare, autosomal recessive neurometabolic disorder that leads to a severe combined deficiency of serotonin, dopamine, norepinephrine and epinephrine. About 100 patients have been described in case reports or case series since the initial description of the index family in 1990. The global incidence of AADCD is unknown, and there are no newborn screening programs. While most patients present a severe phenotype with early onset hypotonia, oculogyric crises, ptosis, dystonia, hypokinesia, impaired development and autonomic dysfunction, a few patients with a milder disease course are known.

Comentários finais

The pathogenic variant of the DDC gene is associated with Aromatic L-Amino acid Decarboxylase enzyme (AADC) deficiency. In the case reported, despite the variant of unknown significance (VUS) on the exome, it was possible to confirm the diagnosis based on the clinical features and other diagnostic tools, such as the enzymatic test, and thus initiate adequate treatment with partial improvement of the symptoms.

Referências

Wassenberg et al. Orphanet Journal of Rare Diseases (2017) 12:12

Fonte de Fomento (se houver)

WASSENBERG, Tessa; et al. Consensus guideline for the diagnosis and treatment of aromatic l-amino acid decarboxylase (AADC) deficiency. Orphanet journal of rare diseases, [S. l.], p. 1-21, 4 abr. 2017.

Palavras Chave

aromatic l-amino acid decarboxylase; Diagnosis; Treatment