Necrotizing enterocolitis and respiratory distress syndrome as first clinical presentation of mitochondrial trifunctional protein deficiency

Eugène F. Diekman, Carolien C. A. Boelen, Berthil H. C. M. T. Prinsen, Lodewijk Ijlst, Marinus Duran, Tom J. de Koning, Hans R. Waterham, Ronald J. A. Wanders, Frits A. Wijburg, Gepke Visser

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: Newborn screening (NBS) for long-chain 3-hydroxy acyl-CoA dehydrogenase (LCHAD) deficiency does not discriminate between isolated LCHAD deficiency, isolated long-chain keto acyl-CoA (LCKAT) deficiency and general mitochondrial trifunctional protein (MTP) deficiency. Therefore, screening for LCHAD deficiency inevitably comprises screening for MTP deficiency, which is much less amenable to treatment. Furthermore, absence of a clear classification system for these disorders is still lacking. Materials and Methods: Two newborns screened positive for LCHAD deficiency died at the age of 10 and 31 days, respectively. One due to severe necrotizing enterocolitis (NEC), cardiomyopathy and multiorgan failure and the other due to severe infant respiratory distress syndrome (IRDS) and hypertrophic cardiomyopathy. (Keto)-acylcarnitine concentration and enzymatic analysis of LCHAD and LCKAT suggested MTP deficiency in both patients. Mutation analysis revealed a homozygous HADHB c.357+5delG mutation in one patient and a homozygous splice-site HADHB mutation c.212+1G>C in the other patient.Data on enzymatic and mutation analysis of 40 patients with presumed LCHAD, LCKAT or MTP deficiency were used to design a classification to distinguish between these disorders. Discussion: NEC as presenting symptom in MTP deficiency has not been reported previously. High expression of long-chain fatty acid oxidation enzymes reported in lungs and gut of human foetuses suggests that the severe NEC and IRDS observed in our patients are related to the enzymatic deficiency in these organs during crucial stages of development.Furthermore, as illustrated by the cases we propose a classification system to discriminate LCHAD, LCKAT and MTP deficiency based on enzymatic analysis
Original languageEnglish
Pages (from-to)1-6
JournalJIMD Reports
Volume7
DOIs
Publication statusPublished - 2013

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