A female case of aromatic l-amino acid decarboxylase deficiency responsive to MAO-B inhibition

A review of aromatic l‐amino acid decarboxylase (AADC) deficiency in Taiwan

“…Compared with literature reports that 95% of patients have hypotonia, 86% experience OGC, and 39% show ptosis, the Taiwanese cohort included 36 of 37 patients (97.3%) with hypotonia, OGC, and ptosis (Brun et al, ; Hwu et al, ; Hwu et al, ). Unlike patients with milder phenotype that may respond to DA agonists, MAO inhibitors, or pyridoxine (Kojima et al, ; Swoboda et al, ; Wassenberg et al, ), patients with severe phenotype (such as with IVS64 + A > T) show poor response to these medication, and none reach motor milestones under treatment with these medications (Hwu et al, ). Death occurs at a mean age of 4.6 years (range 1.0–7.0 years) with 50% of deaths due to multiple organ failure and 20% to sepsis, followed by heart failure and pneumonia (Hwu et al, ).…”

“…Since Hyland and Clayton first reported AADCD in 1990 (Hyland & Clayton, ), only 120 cases of this ultrarare disease have been reported worldwide (Brun et al, ; Dai, Ding, & Fang, ; Portaro et al, ; Sherazi et al, ; Wassenberg et al, ; Zhu & Yu, ). A wide range of clinical presentation, from severe (profound hypotonia, developmental delay, and oculogyric crisis [OGC]), moderate, to mild (mild developmental delay, ambulatory without assistance, mild intellectual disability), or atypical cases, make the diagnosis difficult, though the majority of cases present before 18 months of age with hypotonia or floppiness (Brun et al, ; Kojima et al, ; Portaro et al, ; Spitz et al, ; Wassenberg et al, ). The diagnosis mainly depends on low 5‐hydroxyindoleacetic acid (5‐HIAA), homovanillic acid (HVA), high 3‐ O ‐methyldopa (3‐OMD) and l ‐dopa in the cerebrospinal fluid (CSF), and low plasma AADC enzyme activity, followed by identification of compound heterozygous or homozygous pathogenic variants in the DDC gene (Brun et al, ; Wassenberg et al, ) (Figure ).…”

Trace Amines and Their Receptors

“…A variant on this alternative splicing, in which the non-neuronal variant was spliced to the neuronal acceptor site, has also been suggested in G cells of the rat stomach antrum (Djali et al, 1998), which may indicate cell type-selective plasticity in the control of AADC expression. Recently, a number of cis-acting polymorphisms of AADC have been identified with putative clinical relevance (Li and Meltzer, 2014;Eisenberg et al, 2016), and disease-associated AADC coding variants are also known (Graziano et al, 2015;Kojima et al, 2016;Montioli et al, 2016).…”

Eye movement disorders and neurological symptoms in late‐onset inborn errors of metabolism

“…[89][90][91] Patients with aromatic L-amino acid decarboxylase deficiency (AADC), 21,92 tyrosine hydroxylase deficiency, 93-96 and 6-pyruvoyl-tetrahydropterin synthase deficiency 97,98 may show oculogyric crisis, in particular in AADC in which oculogyric crisis is one of the key features. 92,99,100 Finally, oculogyric crisis is also described in sepiapterin reductase deficiency. [101][102][103] Disorders affecting dopamine transport include brain dopamine-serotonin vesicular disease (vesicular monoamine transporter 2 deficiency) and dopamine transporter deficiency syndrome (DAT deficiency).…”

“…Oculogyric crises are more frequent in recessive than dominant forms of GTP‐CH‐I deficiency . Patients with aromatic L‐amino acid decarboxylase deficiency (AADC), tyrosine hydroxylase deficiency, and 6‐pyruvoyl‐tetrahydropterin synthase deficiency may show oculogyric crisis, in particular in AADC in which oculogyric crisis is one of the key features . Finally, oculogyric crisis is also described in sepiapterin reductase deficiency …”