Olsson David, Barbaro Michela, Haglind Charlotte, Halldin Maria, Lajic Svetlana, Tucci Sara, Zetterström Rolf H, Nordenström Anna
Department of Women's and Children's Health, Unit for Pediatric Endocrinology and Metabolic Disorders Karolinska Institutet/Karolinska University Hospital Stockholm Sweden.
Center for Inherited Metabolic Diseases, CMMS Karolinska University Hospital Stockholm Sweden.
JIMD Rep. 2022 Jan 9;63(2):181-190. doi: 10.1002/jmd2.12268. eCollection 2022 Mar.
Very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) is a recessive disorder of fatty acid beta-oxidation with variable phenotype. Patients may present during the neonatal period with lethal multi-organ failure or during adulthood with a myopathic phenotype. VLCADD is included in the Swedish newborn screening (NBS) program since 2010. The study describes the phenotype and biochemical findings in relation to the genotype, enzyme activity, and screening data in a Swedish cohort of pediatric patients with VLCADD. A total of 22 patients (20 diagnosed via NBS between 2010 and 2019, two diagnosed pre NBS) were included. Parameters analyzed were enzyme activity (palmitoyl CoA oxidation rate); genotype; NBS results including Collaborative Laboratory Integrated Reports (CLIR) score; biochemical findings; treatment; clinical outcome. A clinical severity score (CSS) was compiled using treatment interventions and clinical symptoms. A possible correlation between CSS and VLCAD residual enzyme activity and NBS CLIR score was analyzed. The most common variant (c.848T>C) was identified in 24/44 alleles. Five novel variants were detected. Clinical manifestations varied from asymptomatic to severe. There was a correlation between CSS, residual enzyme activity, and CLIR scores. Most patients diagnosed via NBS had less severe disease compared to those clinically diagnosed. In conclusion, the identified correlation between the NBS CLIR score, residual enzyme activity, and clinical outcome suggests that information available neonatally may aid in treatment decisions.
极长链酰基辅酶A脱氢酶缺乏症（VLCADD）是一种脂肪酸β氧化的隐性疾病，具有可变表型。患者可能在新生儿期出现致命的多器官功能衰竭，或在成年期出现肌病表型。自2010年以来，VLCADD被纳入瑞典新生儿筛查（NBS）项目。该研究描述了瑞典一组患有VLCADD的儿科患者的表型、生化结果与基因型、酶活性和筛查数据之间的关系。共纳入22例患者（20例在2010年至2019年间通过NBS确诊，2例在NBS之前确诊）。分析的参数包括酶活性（棕榈酰辅酶A氧化率）、基因型、NBS结果，包括协作实验室综合报告（CLIR）评分、生化结果、治疗和临床结局。使用治疗干预措施和临床症状编制了临床严重程度评分（CSS）。分析了CSS与VLCAD残余酶活性和NBS CLIR评分之间可能的相关性。在44个等位基因中的24个中鉴定出最常见的变异（c.848T>C）。检测到5个新变异。临床表现从无症状到严重不等。CSS、残余酶活性和CLIR评分之间存在相关性。与临床诊断的患者相比，大多数通过NBS诊断的患者疾病较轻。总之，NBS CLIR评分、残余酶活性和临床结局之间已确定的相关性表明，新生儿期可获得的信息可能有助于治疗决策。
