Department of Pathology and Laboratory Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
Department of Pediatrics and Adolescent Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
Orphanet J Rare Dis. 2024 Aug 29;19(1):315. doi: 10.1186/s13023-024-03325-4.
Fatty acid oxidation defects are rare autosomal recessive disorders with variable clinical manifestations and outcome. Early detection by systematic neonatal screening may improve their prognosis. Long-term outcome studies of these disorders in the Middle East and North Africa region are limited. The purpose of this study is to report the diagnostic challenges and outcome of fatty acid oxidation defects in a major tertiary care center in Lebanon, a resource-constrained country in the Middle East.
A retrospective review of charts of all fatty acid oxidation defects sequential patients diagnosed and followed at our center was conducted. Collected data included: parental consanguinity, age at diagnosis, clinical presentation, biochemical profile, confirmatory diagnosis, treatment and outcome. A genotype-phenotype correlation was also performed, when available.
Seven types of fatty acid oxidation defects were identified in a total of 34 patients from 21 families. Most families (79%) were consanguineous (first-degree cousins). The majority were diagnosed when clinically symptomatic (78%), at various ages between 10 days and 19 years (average: 2 years). Follow-up duration spanned between 2 months and 15 years (average: 5 years). The remainder of the patients were detected while still asymptomatic by systematic neonatal screening (9%) or due to positive family history (9%). The most common defect was carnitine transporter deficiency (50%) with an exclusive cardiac presentation related to a founder variant c.981C > T, (p.Arg254*) in the SLC22A5 gene. Medium chain acyl-CoA dehydrogenase deficiency was found in 13% only, which could be explained by the absence of systematic neonatal screening. Rare gene variants were detected in very long chain and multiple acyl-CoA dehydrogenase deficiency. The worse prognosis was observed in very long chain acyl-CoA dehydrogenase deficiency. The overall survival at last follow-up reached 75% with a complete reversal of symptoms with treatment in most patients (63%), despite their late diagnosis.
Our experience highlights the diagnostic challenges and outcome of fatty acid oxidation defects in a resource-constrained country with high consanguinity rates. Physicians' awareness and systematic neonatal screening are key for diagnosis. Larger genotype-phenotype studies are still needed to understand the natural history of these rare diseases and possibly improve their outcome.
脂肪酸氧化缺陷是罕见的常染色体隐性遗传病，具有不同的临床表现和结局。通过系统的新生儿筛查早期发现，可能改善其预后。中东和北非地区关于这些疾病的长期预后研究有限。本研究旨在报告在黎巴嫩一家主要的三级保健中心诊断脂肪酸氧化缺陷的挑战和结果，黎巴嫩是中东一个资源有限的国家。
对我院确诊并随访的所有脂肪酸氧化缺陷患者的病历进行回顾性分析。收集的数据包括：父母近亲结婚、诊断时的年龄、临床表现、生化特征、明确诊断、治疗和结局。如果有条件，还进行了基因型-表型相关性分析。
共在 21 个家系的 34 名患者中鉴定出 7 种脂肪酸氧化缺陷类型。大多数家系（79%）是近亲结婚（表亲）。大多数患者在出现临床症状时（78%）被诊断，发病年龄在 10 天至 19 岁之间（平均 2 岁）。随访时间从 2 个月到 15 年不等（平均 5 年）。其余的患者在无症状时通过系统的新生儿筛查（9%）或阳性家族史（9%）被发现。最常见的缺陷是肉碱转运体缺陷（50%），表现为与 SLC22A5 基因中的一个独特的创始人变体 c.981C > T（p.Arg254*）相关的心脏特异性表现。中链酰基辅酶 A 脱氢酶缺乏症仅占 13%，这可以解释为没有系统的新生儿筛查。罕见的基因突变见于极长链和多种酰基辅酶 A 脱氢酶缺乏症。极长链酰基辅酶 A 脱氢酶缺乏症的预后较差。在最后一次随访时，75%的患者存活，大多数患者（63%）经治疗后症状完全缓解，尽管诊断较晚。
我们的经验突出了在一个近亲结婚率高、资源有限的国家诊断脂肪酸氧化缺陷的挑战和结果。医生的认识和系统的新生儿筛查是诊断的关键。仍需要更大的基因型-表型研究来了解这些罕见疾病的自然史，并可能改善其预后。
