Study Shows Cognitive Range in AADC Deficiency Patients

Psychiatric disorders were present in all patients studied, but intellectual abilities varied

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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People with AACD deficiency commonly experience emotional problems and intellectual disability, though the severity of cognitive impairment varies markedly among patients, a new study indicates.

“Our study provides further evidence that AADCD requires specific neurological and neuropsychological assessments to monitor the disease,” the study’s researchers wrote.

The study, “Long-term neurological and psychiatric outcomes in patients with aromatic l-amino acid decarboxylase deficiency,” was published in  Parkinsonism and Related Disorders.

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Scientists Test New Method That Can Help Diagnose AADC Deficiency

AADC deficiency is an extremely rare genetic disorder caused by mutations that render the body unable to properly synthesize certain neurotransmitters, chemicals that brain cells use to communicate with each other. The condition can cause a range of symptoms including seizures, emotional and cognitive challenges, and eye movement disorders called oculogyric crises.

Scientists at Sapienza University of Rome, Italy, detailed the symptoms and clinical outcomes of nine people with AACD deficiency, ranging in age from 8 to 40.

“As for other ultrarare diseases, understanding the natural history of AADC [deficiency] is an important prerequisite for designing interventional studies aimed at improving or preventing severe outcomes of this condition,” the researchers wrote.

All nine patients started to display symptoms within the first months after birth, with some even showing earlier abnormalities such as reduced movement during pregnancy. Five were diagnosed in early childhood, between ages 1 and 6. The other four were not formally diagnosed with AADC deficiency until they were in their 20s or 30s, however.

At the most recent examination, all nine patients displayed movement disorders such as involuntary muscle contractions (dystonia). Psychiatric disorders such as anxiety and depression, as well as sleep issues such as awakening during the night, also were reported in all nine patients.

All also showed detectable signs of intellectual disability on standard assessments, though the severity of intellectual disability varied markedly. It was judged mild in three patients, moderate in another three, and severe in the last three.

Given the wide range in cognitive scores, the researchers noted that “cognitive functioning should be specifically examined to avoid its underestimation based on movement disorder severity.”

Higher levels of certain neurotransmitter-related intermediates in the fluid around the brain — specifically homovanillic acid (HVA) and 5-hydroxyindolacetic acid (5-HIAA) — were generally associated with less severe intellectual disability, statistical analyses showed. The researchers emphasized that their analyses were limited by the small number of patients.