The natural history of elevated tetradecenoyl‐L‐carnitine detected by newborn screening in New Zealand: implications for very long chain acyl‐CoA dehydrogenase deficiency screening and treatment. Issue 3 (7th January 2016)

• Record Type: Journal Article
• Authors: Ryder, Bryony; Knoll, Detlef; Love, Donald R.; Shepherd, Phillip; Love, Jennifer M.; Reed, Peter W.; de Hora, Mark; Webster, Dianne; Glamuzina, Emma; Wilson, Callum
• Is Part Of: Journal of inherited metabolic disease. Volume 39:Issue 3(2016)
• Page Start: 409
• Page End: 414
• Publication Date: 2016-01-07
• Subjects: Metabolism, Inborn errors of -- Periodicals; Metabolism -- Disorders -- Periodicals; 616.39042
• DOI: 10.1007/s10545-015-9911-z
• Languages: English
• ISSNs: 0141-8955

Abstract

Abstract: Very long chain acyl‐CoA dehydrogenase deficiency (VLCADD, OMIM #201475) has been increasingly diagnosed since the advent of expanded newborn screening (NBS). Elevated levels of tetradecenoyl‐L‐carnitine (C14:1) in newborn screening blood spot samples are particularly common in New Zealand, however this has not translated into increased VLCADD clinical presentations. A high proportion of screen‐positive cases in NZ are of Maori or Pacific ethnicity and positive for the c.1226C > T (p.Thr409Met) ACADVL gene variant. We performed a retrospective, blinded, case–control study of 255 cases, born between 2006 and 2013, with elevated NBS C14:1 levels between 0.9 and 2.4 μmol/L, below the NZ C14:1 notification cut‐off of 2.5 μmol/L. Coded healthcare records were audited for cases and age‐ and ethnicity‐ matched controls. The clinical records of those with possible VLCADD‐related symptoms were reviewed. The follow‐up period was 6 months to 7 years. Two of 247 cases (0.8 %) had possible VLCADD‐like symptoms while four of 247 controls (2 %) had VLCADD‐like symptoms (p = 0.81). Maori were overrepresented (68 % of the cohort vs 15 % of population). Targeted analysis of the c.1226 locus revealed the local increase in screening C14:1 levels is associated with the c.1226C > T variant (97/152 alleles tested), found predominantly in Maori and Pacific people. There was no increase in clinically significant childhood disease, irrespective of ethnicity. The study suggests that children with elevated C14:1, between 0.9‐2.4 μmol/L, on NBS are at very low risk of clinically significant childhood disease. A minimally interventional approach to managing these patients is indicated, at least in the New Zealand population.