Dataset Information

Prevalence of Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency in Estonia.

ABSTRACT: The aim of our study was to evaluate the prevalence of long chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) in the general Estonian population and among patients with symptoms suggestive of fatty acid oxidation (FAO) defects. We collected DNA from a cohort of 1,040 anonymous newborn blood spot samples. We screened these samples for the presence of the common c.1528G>C mutation in the HADHA gene. Based on the clinical suspicion of FAO defects, we screened suspected individuals since 2004 for the common c.1528G>C mutation in the HADHA gene and since 2008 in addition by tandem mass spectrometric analysis of plasma acylcarnitines. Our results showed that the carrier frequency of the c.1528G>C mutation in the Estonian population is high - 1:173. During the screening of symptomatic patients, we identified five LCHADD patients in four families. Three patients were retrospectively identified by molecular screening of the HADHA gene. One patient was homozygous for the c.1528G>C mutation in the HADHA gene, and two siblings were compound heterozygotes with HADHA genotype c.[1528G>C]+[1690-2A>G]. Among patients tested using acylcarnitine profiling, we identified two cases with an abnormal acylcarnitine profile typical to LCHADD. Molecular analysis showed homozygosity for c.1528G>C mutation. Based on a carrier frequency of 1:173 (95% Confidence Interval 1:76-1:454) and taking into account that the c.1528G>C mutation makes up 87.5% of disease alleles in Estonian LCHADD patients, the estimated prevalence of LCHADD in Estonia would be 1: 91,700.

SUBMITTER: Joost K

PROVIDER: S-EPMC3509831 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Prevalence of Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency in Estonia.

Joost K K Ounap K K Zordania R R Uudelepp M-L ML Olsen R K RK Kall K K Kilk K K Soomets U U Kahre T T

JIMD reports 20110906

The aim of our study was to evaluate the prevalence of long chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) in the general Estonian population and among patients with symptoms suggestive of fatty acid oxidation (FAO) defects. We collected DNA from a cohort of 1,040 anonymous newborn blood spot samples. We screened these samples for the presence of the common c.1528G>C mutation in the HADHA gene. Based on the clinical suspicion of FAO defects, we screened suspected individuals since 200 ...[more]

PMID: 23430857

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Project description:The objective of this prospective cohort study was to determine if dietary therapy including docosahexaenoic acid (DHA; C22:6omega-3) supplementation prevents the progression of the severe chorioretinopathy that develops in children with long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) or trifunctional protein (TFP) deficiency. Physical, biochemical, and ophthalmological evaluations, including electroretinogram (ERG) and visual acuity by evoked potential (VEP), were performed at baseline and annually following the initiation of 65-130 mg/day DHA supplementation and continued treatment with a low-fat diet. Fourteen children with LCHAD or TFP deficiency, 1-12 years of age at enrollment, were followed for 2-5 years. Three subjects with TFP beta-subunit mutations had normal appearance of the posterior pole of the ocular fundi at enrollment and no changes over the course of the study. Eleven subjects who were homozygote and heterozygote for the common mutation, c.1528G>C, had no change to severe progression of atrophy of the choroid and retina with time. Of these, four subjects had marked to severe chorioretinopathy associated with high levels of plasma hydroxyacylcarnitines and decreased color, night and/or central vision during the study. The plasma level of long-chain 3-hydroxyacylcarnitines, metabolites that accumulate as a result of LCHAD and TFP deficiency, was found to be negatively correlated with maximum ERG amplitude (Rmax) (p=0.0038, R2=0.62). In addition, subjects with sustained low plasma long-chain 3-hydroxyacylcarnitines maintained higher ERG amplitudes with time compared to subjects with chronically high 3-hydroxyacylcarnitines. Visual acuity, as determined with the VEP, appeared to increase with time on DHA supplementation (p=0.051) and there was a trend for a positive correlation with plasma DHA concentrations (p=0.075, R2=0.31). Thus, optimal dietary therapy as indicated by low plasma 3-hydroxyacylcarnitine and high plasma DHA concentrations was associated with retention of retinal function and visual acuity in children with LCHAD or TFP deficiency.

Project description:BackgroundMitochondrial trifunctional protein (MTP) and long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiencies are rare fatty acid ?-oxidation disorders. Without dietary management the conditions are life-threatening. We conducted a systematic review to investigate whether pre-symptomatic dietary management following newborn screening provides better outcomes than treatment following symptomatic detection.MethodsWe searched Web of Science, Medline, Pre-Medline, Embase and the Cochrane Library up to 23rd April 2018. Two reviewers independently screened titles, abstracts and full texts for eligibility and quality appraised the studies. Data extraction was performed by one reviewer and checked by another.ResultsWe included 13 articles out of 7483 unique records. The 13 articles reported on 11 patient groups, including 174 people with LCHAD deficiency, 18 people with MTP deficiency and 12 people with undifferentiated LCHAD/MTP deficiency. Study quality was moderate to weak in all studies. Included studies suggested fewer heart and liver problems in screen-detected patients, but inconsistent results for mortality. Follow up analyses compared long-term outcomes of (1) pre-symptomatically versus symptomatically treated patients, (2) screened versus unscreened patients, and (3) asymptomatic screen-detected, symptomatic screen-detected, and clinically diagnosed patients in each study. For follow up analyses 1 and 2, we found few statistically significant differences in the long-term outcomes. For follow up analysis 3 we found a significant difference for only one comparison, in the incidence of cardiomyopathy between the three groups.ConclusionsThere is some evidence that dietary management following screen-detection might be associated with a lower incidence of some LCHAD and MTP deficiency-related complications. However, the evidence base is limited by small study sizes, quality issues and risk of confounding. An internationally collaborative research effort is needed to fully examine the risks and the benefits to pre-emptive dietary management with particular attention paid to disease severity and treatment group.

Dataset Information

Prevalence of Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency in Estonia.

Publications

Prevalence of Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency in Estonia.

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