AADC deficiency from infancy to adulthood: Symptoms and developmental outcome in an international cohort of 63 patients.

Aromatic l-amino acid decarboxylase deficiency (AADCD) is a rare, autosomal recessive neurodevelopmental disorder characterized by impaired synthesis of dopamine, noradrenaline, adrenaline and serotonin, leading to a complex syndrome of motor, behavioral, and autonomic symptoms. This retrospective study assessed the symptoms and developmental outcome of a large international cohort of patients with AADCD via physician and/or caregiver responses to a detailed, standardized questionnaire. Sixty-three patients (60% female; ages 6 months-36 years, median 7 years; 58 living) from 23 individual countries participated. Common symptoms at onset (median age 3 months, range 0-12 months) were hypotonia, developmental delay, and/or oculogyric crises. Oculogyric crises were present in 97% of patients aged 2 to 12 years, occurred in the majority of patients in all age groups, and tended to be most severe during early childhood. Prominent non-motor symptoms were sleep disturbance, irritable mood, and feeding difficulties. The majority of subjects (70%) had profound motor impairment characterized by absent head control and minimal voluntary movement, while 17% had mild motor impairment and were able to walk independently. Dopamine agonists were the medications most likely to produce some symptomatic benefit, but were associated with dose-limiting side effects (dyskinesia, insomnia, irritability, vomiting) that led to discontinuation 25% of the time. The age distribution of our cohort (70% of subjects under age 13 years) and the observation of a greater proportion of patients with a more severe disease phenotype in the younger compared to the older patients, both suggest a significant mortality risk during childhood for patients with severe disease.

Long-term Follow-up of Pulmonary Function and Scoliosis in Patients With Duchenne's Muscular Dystrophy and Spinal Muscular Atrophy.

BACKGROUND: Spine surgery for neuromuscular scoliosis in patients with Duchenne's Muscular Dystrophy (DMD) and Spinal Muscular Atrophy (SMA) remained controversial. This study aimed to review the long-term results of spine surgery and its effect on pulmonary function in these patients. METHODS: A retrospective review was conducted for the above patients who had undergone surgery from 1990 to 2006 in a tertiary hospital. Their yearly lung function tests, clinical records, and x-ray films before and after surgery were reviewed. All patients had at least 2 lung function tests performed before surgery and at least 3 lung function tests performed after surgery. Records of perioperative pulmonary infections that resulted in hospital admissions were also retrieved from the hospital computer system. RESULTS: Forty patients were reviewed: 29 with DMD, 11 with SMA. The mean follow-up period was 11.6 years. For patients with DMD, the mean correction of Cobb's angle from surgery was 34.1 degrees. The rate of decline of the predicted forced vital capacity preoperatively was 7.80% per year, and was reduced to 4.26% per year postoperatively (P<0.001). For patients with SMA, the mean correction of Cobb's angle from surgery was 44.1 degrees. The rate of decline of the predicted forced vital capacity preoperatively was 5.31% per year, and was reduced to 1.77% per year postoperatively (P<0.001). For both DMD and SMA patients, the difference between the rate of preoperative and postoperative pulmonary infections that resulted in hospital admission were, however, not significant (P=0.433 and 0.452, respectively). CONCLUSIONS: Scoliosis surgery in patients with DMD and SMA results in a long-term decreased rate of decline in pulmonary function over a follow-up period of more than 10 years. The level of the apical vertebrae of the scoliosis did not demonstrate a significant trend on the pulmonary function. The frequency of chest infections did not improve by scoliosis surgery. LEVEL OF SIGNIFICANCE: Level III­Retrospective study.