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IEMbase 0100: DDC-related aromatic L-amino acid decarboxylase deficiency

Scope

Field Value
IEMbase ID 100
Nosology 23.1.02.01
Gene DDC
External IDs OMIM:608643
Generated mapping AMBIGUOUS
Candidate DisMech targets Aromatic_L_Amino_Acid_Decarboxylase_Deficiency.yaml; Disorder_of_Catecholamine_Synthesis.yaml#Aromatic L-amino acid decarboxylase deficiency
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents this as autosomal recessive DDC/AADC deficiency in the monoamine neurotransmission group. Treatability is marked yes.

The characteristic biochemical rows are decreased CSF MHPG, decreased CSF 5-HIAA, increased CSF 5-hydroxytryptophan, decreased CSF homovanillic acid, and increased CSF L-dopa. The clinical rows are developmental delay, dysarthria, dystonia, hyperkinesia, and insomnia.

Treatments are monoamine oxidase inhibitors, folinic acid, gene therapy, L-dopa plus carbidopa depending on mutation, and pyridoxine.

DisMech phenotype coverage

The generated AMBIGUOUS status is caused by two legitimate local matches. The canonical target should be the standalone Aromatic_L_Amino_Acid_Decarboxylase_Deficiency.yaml entry, with Disorder_of_Catecholamine_Synthesis.yaml#Aromatic L-amino acid decarboxylase deficiency retained as umbrella context.

The standalone entry covers biallelic DDC variants, AADC enzymatic deficiency, combined serotonin/dopamine/norepinephrine/epinephrine synthesis failure, decreased CSF HVA, decreased CSF 5-HIAA, increased 3-O-methyldopa, motor circuit dysfunction, dysautonomia, and neurodevelopmental impairment. It includes dysarthria, dystonia, oculogyric crisis, hypotonia, hypokinesia, ptosis, developmental delay, autonomic features, and disease-directed eladocagene exuparvovec gene therapy plus pyridoxine, dopamine agonist, and MAO-inhibitor pharmacotherapy.

Concordance and completeness

Judgement: ambiguous generated mapping, but high concordance after selecting the standalone AADC deficiency entry.

IEMbase is more explicit about the CSF compartment for MHPG, 5-HIAA, 5-hydroxytryptophan, HVA, and L-dopa, and includes folinic acid and the mutation-dependent L-dopa/carbidopa row. DisMech is substantially richer for mechanism, autonomic and ocular-motor features, broader phenotype evidence, and approved gene therapy.

Curation actions

  • Resolve to Aromatic_L_Amino_Acid_Decarboxylase_Deficiency.yaml as the canonical disease target.
  • Keep Disorder_of_Catecholamine_Synthesis.yaml#Aromatic L-amino acid decarboxylase deficiency as secondary umbrella context.
  • Consider adding IEMbase-specific CSF MHPG, 5-hydroxytryptophan, and L-dopa biomarker rows if the standalone entry is further normalized.