Impact of Newborn Screening and Early Dietary Management on Clinical Outcome of Patients with Long Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency and Medium Chain Acyl-CoA Dehydrogenase Deficiency-A Retrospective Nationwide Study

Nutrients. 2021 Aug 24;13(9):2925. doi: 10.3390/nu13092925.

Abstract

Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD/MTPD) and medium chain acyl-CoA dehydrogenase deficiency (MCADD) were included in the expanded neonatal screening program (ENBS) in Czechia in 2009, allowing for the presymptomatic diagnosis and nutritional management of these patients. The aim of our study was to assess the nationwide impact of ENBS on clinical outcome. This retrospective study analysed acute events and chronic complications and their severity in pre-ENBS and post-ENBS cohorts. In total, 28 children (12 before, 16 after ENBS) were diagnosed with LCHADD/MTPD (incidence 0.8/100,000 before and 1.2/100,000 after ENBS). In the subgroup detected by ENBS, a significantly longer interval from birth to first acute encephalopathy was observed. In addition, improvement in neuropathy and cardiomyopathy (although statistically non-significant) was demonstrated in the post-ENBS subgroup. In the MCADD cohort, we included 69 patients (15 before, 54 after ENBS). The estimated incidence rose from 0.7/100,000 before to 4.3/100,000 after ENBS. We confirmed a significant decrease in the number of episodes of acute encephalopathy and lower proportion of intellectual disability after ENBS (p < 0.0001). The genotype-phenotype correlations suggest a new association between homozygosity for the c.1528C > G variant and more severe heart involvement in LCHADD patients.

Keywords: clinical outcome; fatty acid oxidation disorders; neonatal screening program; severity assessment.

MeSH terms

  • 3-Hydroxyacyl CoA Dehydrogenases / deficiency
  • Acyl-CoA Dehydrogenase / deficiency*
  • Cardiomyopathies / diagnosis*
  • Cardiomyopathies / diet therapy*
  • Cardiomyopathies / epidemiology
  • Carnitine / analogs & derivatives
  • Carnitine / blood
  • Child
  • Child, Preschool
  • Czech Republic / epidemiology
  • Female
  • Humans
  • Incidence
  • Infant
  • Infant, Newborn
  • Lipid Metabolism, Inborn Errors / diagnosis*
  • Lipid Metabolism, Inborn Errors / diet therapy*
  • Lipid Metabolism, Inborn Errors / epidemiology
  • Male
  • Metabolism, Inborn Errors / diagnosis
  • Mitochondrial Myopathies / diagnosis*
  • Mitochondrial Myopathies / diet therapy*
  • Mitochondrial Myopathies / epidemiology
  • Mitochondrial Trifunctional Protein / deficiency*
  • Neonatal Screening / methods*
  • Nervous System Diseases / diagnosis*
  • Nervous System Diseases / diet therapy*
  • Nervous System Diseases / epidemiology
  • Outcome Assessment, Health Care
  • Retrospective Studies
  • Rhabdomyolysis / diagnosis*
  • Rhabdomyolysis / diet therapy*
  • Rhabdomyolysis / epidemiology
  • Severity of Illness Index

Substances

  • acylcarnitine
  • 3-Hydroxyacyl CoA Dehydrogenases
  • Acyl-CoA Dehydrogenase
  • Mitochondrial Trifunctional Protein
  • Carnitine

Supplementary concepts

  • 3-Hydroxyacyl-CoA Dehydrogenase Deficiency
  • Medium chain acyl CoA dehydrogenase deficiency
  • Trifunctional Protein Deficiency With Myopathy And Neuropathy