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

• Published in: European journal of pediatrics Vol. 182; no. 6; pp. 2535 - 2545
• Main Authors: Abukhaled, Musaad, Al Muqbil, Mohammed, Alghamdi, Malak Ali, Hundallah, Khalid, Suleiman, Jehan, Ben-Omran, Tawfeg, Alfadhel, Majid, Almannai, Mohammed, Alsaleh, Rehab, Tabarki, Brahim
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-06-2023; Springer Nature B.V
• Subjects: Age; Amine oxidase (flavin-containing); Amino Acid Metabolism, Inborn Errors - diagnosis; Amino Acid Metabolism, Inborn Errors - genetics; Amino Acid Metabolism, Inborn Errors - therapy; Amino acids; Aromatic-L-amino-acid decarboxylase; Aromatic-L-Amino-Acid Decarboxylases - genetics; Aromatic-L-Amino-Acid Decarboxylases - therapeutic use; Case reports; Diagnosis; Dopamine Agonists - therapeutic use; Exons; Gene therapy; Humans; Literature reviews; Medical diagnosis; Medicine; Medicine & Public Health; Metabolic disorders; Mutation; Patients; Pediatrics; Vitamin B6; Middle East; Case report; Delayed diagnosis; Whole exome sequencing; Developmental delay; AADC deficiency
• ISSN: 1432-1076; 0340-6199; 1432-1076
• DOI: 10.1007/s00431-023-04886-5

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.