Diagnosis of aromatic L-amino acid decarboxylase deficiency via neurodevelopmental disorder gene panel screening in a patient with atypical presentation

*Correspondence: [e-mail].

Abstract

Case Presentation: S.C.R., a 13-year-old male, delivered vaginally, had delayed cry at birth and difficulty sucking. Since age 1 year, he had speech delay and difficulty socializing. At 6 years of age, he was referred to a neuropediatrician due to learning difficulties, with the complaint that he spent much time staring upward and performed activities slowly. At age 13, he began to have brief episodes of upward gaze deviation, body tremors, and loss of consciousness. He also had persistent nasal obstruction, in addition to a constant feeling of tiredness, muscle weakness, and recurrent diarrhea since childhood. Physical examination showed hyperemic skin lesions on the elbows and legs, unrelated to trauma, drooping shoulders, and decreased tone. Tests: Electroencephalogram, to investigate the occurrence of seizures, showed multifocal epileptiform discharges, and genetic testing was ordered for suspected genetic disease. The panel revealed L-amino acid decarboxylase (AADC, OMIM 608643) deficiency, with detection of two heterozygous variants in the DDC gene (dopa decarboxylase, OMIM 107930): chr7:50.529.209 T>TGATCG and chr7:50.495.371 T>A. Additionally, genetic testing was performed on his mother and brother, which detected the presence of the variant chr7:50.529.209 T>TGATCG in the DDC gene in heterozygosis and the absence of the variant chr7:50.495.371 T>A in his mother, whereas his brother carried the variant chr7:50.495.371 T>A in the DDC gene in heterozygosis but not the variant chr7:50.529.209 T>TGATCG.

Discussion: AADC deficiency is an autosomal recessive metabolic disorder caused by mutations in the DDC gene that lead to decreased levels of neurotransmitters such as dopamine, serotonin, epinephrine, and norepinephrine, which regulate the sympathetic nervous system, mood, cognition, and motor coordination. Symptoms usually emerge in the third month of life and include oculogyric crises, eyelid ptosis, hypotonia, motor delay, variable movement disorders, diarrhea, constipation, nasal congestion, gastroesophageal reflux, and hypoglycemia.

Final Comments: AADC deficiency is a rare disease with variable symptoms. The importance of this report lies in drawing attention to the need for genetic testing in patients with movement disorders, hypotonia, and developmental delay of unknown etiology, ensuring accurate diagnosis and treatment. The diagnoses were performed through diagnostic support programs of PTC Farmacêutica.

Publication History

Article published online:
12 May 2025