Recent Review Confirms Most Common Signs of AADC Deficiency
More than 41 reports were examined for symptoms, treatments for disease
A review of recent medical literature confirmed low muscle tone, developmental delays, and oculogyric crises — when the gaze becomes fixed upward due to spasms in the eye muscles — are all hallmark signs of aromatic l-amino acid decarboxylase (AADC) deficiency, with symptom onset occurring within 6 months of age in most cases.
According to researchers, this update will improve awareness of the condition and help neurologists provide an early and accurate diagnosis to ensure prompt treatment.
The review, “Clinical Features in Aromatic L-Amino Acid Decarboxylase (AADC) Deficiency: A Systematic Review,” was published in the journal Behavioural Neurology.
AADC deficiency is characterized by a wide range of symptoms that can vary from mild to severe. As a result, it is essential clinicians understand the often subtle signs of the condition to ensure prompt and accurate diagnosis and the start of early treatment to improve long-term outcomes.
Researchers in Italy reviewed the recent literature to provide an update on AADC deficiency characteristics to highlight early diagnostic keys that may be helpful to pediatric neurologists.
The review included 41 published reports of patients’ descriptions, including 18 case studies, 10 case series, eight original articles, three short communications, and one each of a comparative analysis and a retrospective (looking back) study.
Data from 261 patients were analyzed, including 117 females, 112 males, and 32 unknown sex. The age of onset was documented in 194 cases. AADC deficiency was identified in nine patients at birth, 40 patients within the third month, 181 within six months, 11 patients between six months and one year, and two beyond one year.
Hypotonia, or low muscle tone, was present in 193 individuals (74%), while developmental delays were recorded in 188 cases (72%). Oculogyric crises were seen in 177 patients (68%).
Autonomic symptoms were present in 138 patients (53%), which include disturbances in the parts of the nervous system that control involuntary functions, such as excessive sweating, drooping eyelids, and low blood pressure. The movement disorder hypokinesia (reduced motor activity) was seen in 110 patients (42%), sleep disorders in 96 (37%), and involuntary muscle contractions (dystonia) occurred in 93 cases (36%).
Behavioral disorders were mentioned in 79 cases (30%), drooping eyelids (ptosis) were present in 68 patients (26%), digestive problems in 50 (19%), low blood glucose in 26 (4.6%%), and epilepsy occurred in 12 cases.
Among the 201 cases with available information on a genetic diagnosis, 119 carried two different mutations in each of their DDC genes (compound heterozygous). At the same time, 82 had the same mutations in both DDC genes (homozygous). Ethnic origin among those with homozygous variants was recorded for 51 patients, which included 34 Asians, 12 Caucasians, three Arabs, one Indian, and one Turk.
Analysis of cerebrospinal fluid, the clear liquid around the brain and spinal cord, was available for 92 patients, and all showed patterns typical of AADC deficiency. The activity of the AADC enzyme encoded by the DCC gene was low, and 3-OMD, a byproduct generated by a lack of enzyme activity, was elevated.
Images of the nervous system were obtained for 91 patients, with 55 showing typical results and 36 with volume changes or white matter abnormalities. Of the available electroencephalogram (EEG) recordings to measure brain electrical activity, 52 were normal, and 23 demonstrated nonspecific changes, such as an abnormal background. Four patients had activities related to epileptic seizures.
Treatments for AADC deficiency
Regarding AADC deficiency treatments, improvements were seen in 49 of 128 (38%) who received vitamin B6, 82 of 149 (55%) with dopamine receptor agonists, and 35 out of 62 (56%) patients treated with monoamine oxidase inhibitors. All 10 patients undergoing gene therapy demonstrated improved cognitive and motor performance.
Overall, 13 patients died (5%): five due to pneumonia, two due to complications during oculogyric crises, one caused by a heart attack, one due to sepsis, and four without a reported cause. Six patients died younger than 3 years of age, two younger than 10 years old, one between 10 and 20 years of age, two older than 20, and two unspecified.
“We confirmed the core clinical features of … AADC deficiency, highlighting the commonest neurologic and nonneurologic signs and symptoms, the whole phenotypic spectrum from milder to severe forms, and the best currently available diagnostic and therapeutic approaches,” the researchers concluded. “Our review will provide paediatric neurologists with an updated description of the most relevant literature data to increase awareness of this rare disorder, with the aim not to miss diagnoses and to improve long-term outcomes by prompt treatment initiation.”
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