Neurotransmitter disorders

Gene: DDC

Green List (high evidence)

The DDC gene codes for the enzyme aromatic L-amino acid decarboxylase (AADC) which is responsible for the synthesis of L-dopa into dopamine and 5-HTP into serotonin. Pathogenic variants lead to Aromatic L-amino acid decarboxylase deficiency (AADCD), which is a rare autosomal recessive neurometabolic disorder. So far, in 123 known patients, 79 disease-causing variants in the DDC gene have been described and listed in the locus specific database PNDdb (http://biopku.org/home/pnddb.asp ) (Himmelreich, 2019). Patients with AADCD have a severe combined deficiency of serotonin, dopamine, norepinephrine and epinephrine. Most common signs and symptoms, according to the consensus paper of Wassenberg et al. (2017), are hypotonia, movement disorders, developmental delay and autonomic symptoms. Between movement disorders manifestations, oculogyric crisis (91/117 patients, 78%), dystonia (63/177 p, 54%) and hypokinesia (40/117 p, 34%) are the most described. Often reported autonomic signs are ptosis, excessive sweating, and nasal congestion (no numbers given).

Created: 25 Feb 2020, 1:11 p.m. | Last Modified: 25 Feb 2020, 1:11 p.m.

Panel Version: 1.4

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Aromatic L-amino acid decarboxylase deficiency 608643; floppy child; dystonia; hypotonia; developmental delay; oculogyric crisis

Publications

• 28100251
• 30952622

Comment on publications: 27830117

Created: 25 May 2017, 4:27 p.m.

Comment on list classification: Changed status to Green due to expert review and evidence in the literature to support the phenotype

Created: 25 May 2017, 9:22 a.m.

Comment on publications: In OMIM and as a confirmed Developmental Disorder Gene / G2P. At least 7 variants reported.

Created: 25 May 2017, 9:16 a.m.

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal