Aromatic L-amino acid decarboxylase deficiency in countries in the Middle East: a case series and literature review.

Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare inherited neurometabolic disorder that can lead to severe physical and developmental impairment. This report includes 16 patients from the Middle East and is the largest series of patients with confirmed AADC deficiency from this region reported to date. The patients displayed a range of signs and symptoms at presentation and almost all failed to reach major motor milestones. Missed and delayed diagnoses were common leading to the late introduction of targeted treatments. Eight unique variants were identified in the DDC gene, including six missense and two intronic variants. A previously undescribed variant was identified: an intronic variant between exons 13 and 14 (c.1243-10A>G). The patients were mostly treated with currently recommended medications, including dopamine agonists, vitamin B6, and monoamine oxidase inhibitors. One patient responded well, but treatment outcomes were otherwise mostly limited to mild symptomatic improvements. Five patients had died by the time of data collection, confirming that the condition is associated with premature mortality. There is an urgent need for earlier diagnosis, particularly given the potential for gene therapy as a transformative treatment for AADC deficiency when provided at an early age.  Conclusions: Delays in the diagnosis of AADC deficiency are common. There is an urgent need for earlier diagnosis, particularly given the potential for gene therapy as a transformative treatment for AADC deficiency when provided at an early age. What is Known: • Aromatic L-amino acid decarboxylase deficiency is a rare neurometabolic disorder that can lead to severe physical and developmental impairment. • Currently recommended medications provide mostly mild symptomatic improvements. What is New: • The clinical presentation of sixteen patients with confirmed AADC deficiency varied considerably and almost all failed to reach major motor milestones. • There is an urgent need for earlier diagnosis, given the potential for gene therapy as a transformative treatment for AADC deficiency when provided at an early age.

Patient demographics and characteristics from an ambispective, observational study of patients with duchenne muscular dystrophy in Saudi Arabia.

Duchenne muscular dystrophy (DMD) is a rare neuromuscular disorder that is characterized by progressive muscle weakness, resulting in disability and premature death. Onset of symptoms typically occurs at 2-3 years of age, and disease progression is managed through treatment with corticosteroids. The aim of this interim analysis is to increase disease awareness and improve patient management in Saudi Arabia (SA) through the use of data from an ongoing ambispective, observational, multicenter study evaluating characteristics of patients aged 1-14 years with genetically confirmed DMD in SA. This interim analysis examined the secondary outcomes from the study-the demographics and clinical characteristics of patients included retrospectively [data recorded (enrollment visit) between January 2014 and September 2020] and prospectively between September 2020 and April 2021. The primary outcome-the list of DMD gene mutations for the study population-will be reported at a later date. There were 177 eligible patients. Mean, standard deviation (SD) age at enrollment was 7.5 (3.0) years. Median (min, max) age at diagnosis was 7.0 (1.3, 13.8) years. At enrollment, 28.9% of patients were full-time wheelchair users, 50.0% of ambulatory patients could run, and 63.9% could climb stairs. The mean (SD) ages of patients at enrollment who were unable to run and climb stairs were 8.0 (2.7) and 7.6 (3.0) years, respectively. Speech delay (19.4%) and learning difficulties (14.9%) were the most commonly reported intellectual impairments. Physical therapy (84.2%) was the most common choice for initial management of DMD. Only 40.7% of patients received corticosteroid therapy as part of their initial management plan, rising to 59.1% at enrollment. Devices were given to 28.8% of patients for initial management, most commonly ankle-foot orthoses (26.0%) and wheelchairs (6.2%). This analysis reports data from the largest study to date to capture demographics and clinical characteristics of DMD patients in SA. The interim results show a relatively late DMD diagnosis age compared with that in other countries, and a need for improved adherence to international DMD standard of care guidelines. Therefore, there is an urgent requirement for improved DMD education and awareness among healthcare professionals and the public in SA.