Abstract
Background: Very long chain acyl CoA dehydrogenase (VLCAD) deficiency (OMIM#201475) is an autosomal recessive disorder of fatty acid beta oxidation caused by defect in the ACADVL. The aim of this study was to analyze the clinical, biochemical, and molecular features of VLCAD deficiency in Saudi Arabia, including the treatment and outcome.
Methods: We carried out a retrospective chart review analysis of 37 VLCAD deficiency patients from two tertiary centers in Saudi Arabia, over a 14-year period (2002–2016). Twenty-three patients were managed at King Abdul-Aziz Medical City and fourteen patients at King Fahad Medical City.
Results: Severe early onset VLCAD deficiency is the most frequent phenotype in our patients, caused by four different mutations in ACADVL; 31 patients (83.7%) had a homozygous nonsense mutation in exon 2 of ACADVL c.65C>A;p. Ser22X. Twenty-three patients died before the age of 2 years, despite early detection by newborn screening and implementation of treatment, including supplementation with medium chain triglycerides.
Conclusion: This study reports the clinical, biochemical, molecular findings, treatment, and outcome of patients with VLCAD deficiency over the last 14 years. We identified the most common variant and one new variant in ACADVL. Despite early diagnosis and treatment, the outcome of VLCAD deficiency in this Saudi Arabian population remains poor. Preventive measures, such as prenatal diagnosis, could be implemented.
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Acknowledgments
The authors would like to thank the patients and their families. The authors would also like to extend their acknowledgment to Ms. Rasha Al-kindi for her support in data collection.
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Communicated by: Verena Peters
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Learning Point
Truncating null mutations was the most common genotype in our VLCAD deficiency patients, with poor outcome despite early diagnosis and proper management. Prenatal diagnosis be a preferable strategy for managing this disorder in our population.
Details of the Contributions of Individual Authors
AO: performed the majority of work associated with preparing, writing, and submitting the manuscript and contributed to the clinical diagnosis and management of the patient. MN: performed work associated with preparing, writing, and intellectual discussion. MF, AAS, and FM: contributed to the diagnosis and management of the patient at KAMC and edited the manuscript. AAA, EF, and AM: contributed to the clinical diagnosis and management of the patient at KFMC and edited the manuscript. DM: Study design, manuscript writing, and final revision. MAB and MAA: Data collection and manuscript revision. WE: contributed to the clinical diagnosis and management of the patient and performed the work related to study design, conceptual discussion, and manuscript writing and revision. All authors read and approved the final manuscript.
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Wafaa Eyaid.
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Conflict of Interest
Abdulrahman Obaid, Marwan Nashabat, Majid Alfadhel, Ali Alasmari, Fuad Al Mutairi, Abdulrahman Alswaid, Eissa Faqeih, Aziza Mushiba, Deborah Marsden, Marwah Albanyan, Maryam Alalwan, and Wafaa Eyaid declare that they have no conflict of interest.
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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all parents and available upon request.
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This study was approved by King Abdullah International Medical Research Center IRB (RC16/189/R).
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This study received no specific funding from any financial support agency either public or commercial and not-for-profit sectors.
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Obaid, A. et al. (2017). Clinical, Biochemical, and Molecular Features in 37 Saudi Patients with Very Long Chain Acyl CoA Dehydrogenase Deficiency. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 40. JIMD Reports, vol 40. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2017_58
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DOI: https://doi.org/10.1007/8904_2017_58
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