Obaid Abdulrahman, Nashabat Marwan, Alfadhel Majid, Alasmari Ali, Al Mutairi Fuad, Alswaid Abdulrahman, Faqeih Eissa, Mushiba Aziza, Albanyan Marwah, Alalwan Maryam, Marsden Deborah, Eyaid Wafaa
Genetics Division, Department of Pediatrics, King Abdullah International Medical Research Centre, King Saud bin Abdulaziz University for Health Science, King Abdulaziz Medical City, Ministry of National Guard-Health Affairs (NGHA), Riyadh, Saudi Arabia.
Medical Genetic Section, King Fahad Medical City, Children's Hospital, Riyadh, Saudi Arabia.
JIMD Rep. 2018;40:47-53. doi: 10.1007/8904_2017_58. Epub 2017 Oct 5.
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.
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.
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.
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.
极长链酰基辅酶A脱氢酶（VLCAD）缺乏症（OMIM#201475）是一种由ACADVL缺陷引起的常染色体隐性脂肪酸β氧化障碍疾病。本研究旨在分析沙特阿拉伯VLCAD缺乏症的临床、生化和分子特征，包括治疗方法和治疗结果。
我们对沙特阿拉伯两个三级医疗中心在14年期间（2002 - 2016年）的37例VLCAD缺乏症患者进行了回顾性病历分析。23例患者在阿卜杜勒 - 阿齐兹国王医疗城接受治疗，14例患者在法赫德国王医疗城接受治疗。
严重早发型VLCAD缺乏症是我们患者中最常见的表型，由ACADVL中的四种不同突变引起；31例患者（83.7%）在ACADVL外显子2中有纯合无义突变c.65C>A；p.Ser22X。尽管通过新生儿筛查早期发现并实施了包括补充中链甘油三酯在内的治疗，但仍有23例患者在2岁前死亡。
本研究报告了过去14年中VLCAD缺乏症患者的临床、生化、分子学发现、治疗方法及治疗结果。我们在ACADVL中鉴定出最常见的变异和一种新变异。尽管进行了早期诊断和治疗，但沙特阿拉伯人群中VLCAD缺乏症的治疗结果仍然很差。可以实施产前诊断等预防措施。
