AADC deficiency is a rare, devastating disorder of the central nervous system

Aromatic L-amino Acid Decarboxylase (AADC) deficiency is a genetic disease associated with defects in neurotransmitter synthesis, resulting in life-limiting motor and autonomic dysfunction, developmental delay, and premature death1-3

AADC deficiency can manifest with a broad spectrum of symptoms. The most common are1-3:

  • Hypotonia
  • Developmental delay
  • Movement disorders, especially oculogyric crisis.

In the published consensus guidelines:

  • Mean age of onset for patients with AADC deficiency is 2.7 months (n=68)2
  • Despite this young age of symptom onset, the mean age of diagnosis is 3.5 years (n=68)2

Symptoms typically do not improve, leading to the need for lifelong care1,3

  • Patients who live to adulthood suffer long-term cardiac and orthopedic complications and increased risk of infections2
  • Body weight may be normal in the first few months, but growth and weight gain can slow after the first year4

AADC deficiency can affect patients of any gender, ethnic origin, or geographic region2,4

AADC deficiency has been reported in individuals of Asian, Caucasian, Arabic, Iranian, and Jewish ethnic origin2,a.

aBased on 117 patients with AADC deficiency as reported in a literature review2

AADC is an enzyme required for biosynthesis of dopamine and serotonin2,3,5,6

  • In the autosomal recessive disease AADC deficiency, mutations in the dopa decarboxylase (DDC) gene result in reduced AADC enzyme activity, leading to severe combined deficiency of the neurotransmitters dopamine, serotonin, norepinephrine, and epinephrine2,3,5,6
  • The result is an increase in L-dopa, 3-OMD, and 5-HTP, and a decrease in the neurotransmitter metabolites HVA and 5-HIAA2,3,5,6

Adapted from Wassenberg 2017.2
3-OMD=3-O-methyldopa; 5-HIAA=5-hydroxyindoleacetic acid; 5-HTP=5-hydroxytryptophan; HVA=homovanillic acid; L-dopa=L-3,4-dihydroxyphenylalanine; VLA=vanillactic acid.