Nutrition management guideline for very-long chain acyl-CoA dehydrogenase deficiency (VLCAD): An evidence- and consensus-based approach

Calcar, Sandra C. Van; Sowa, Mary; Rohr, Frances J.; Beazer, J.; Setlock, T.; Weihe, T.U.; Pendyal, Surekha; Wallace, Lee Shelly; Hansen, Joyanna; Stembridge, Adrya; Splett, Patricia L.; Singh, Rani H.

doi:10.1016/j.ymgme.2020.10.001

Cited by 42 publications

(64 citation statements)

References 96 publications

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“…This disorder leads to an accumulation of C14:1 and other long-chain acylcarnitines. A genetic defect of the enzyme is known for humans [for review see van Calcar et al ( 23 )] and for dogs ( 24 ). However, this has not yet been observed in horses.…”

Section: Discussionmentioning

confidence: 99%

Severe Inhibition of Long-Chain Acyl-CoA Enoylhydratase (EC 4.2.1.74) in a Newborn Foal Suffering From Atypical Myopathy

2021

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In horses, congenital defects of energy production from long-chain fatty acids have not been described so far. In contrast, inhibition of fatty acid degradation caused by the toxins hypoglycin A and methylenecyclopropylglycine from various maple species are observed frequently. These non-proteinogenic aminoacids are passed on placentally to fetuses or with collostrum or milk to newborn foals. Nevertheless, newborn foals become very rarely symptomatic. Vertical transmission apparently is not sufficient to induce clinical disease without a particular genetic constellation being present. One of these rare cases was investigated here using samples from a mare and her foal. Intoxication by hypoglycin A and methylenecyclopropylglycine is also of interest to human pathology, because these toxins have caused fatal poisonings after consumption of certain fruits many times, especially in children. Maple toxins, their metabolites and some short-chain acyl compounds were quantified by ultrahigh-pressure liquid chromatography/tandem mass spectrometry. An comprehensive spectrum of long-chain acylcarnitines was prepared using electrospray ionization tandem mass spectrometry. Organic acids and acylglycines were determined by gas chromatography mass spectrometry. For evaluation, results of other horses poisoned by maple material as well as unaffected control animals were used. In the serum of the foal, hypoglycin A was detected at a low concentration only. Toxin metabolites reached <3.5% of the mean of a comparison group of horses suffering from atypical myopathy. The spectrum of acylcarnitines indicated enzyme inhibition in short-chain and medium-chain regions typical of acer poisoning, but the measured concentrations did not exceed those previously found in clinically healthy animals after maple consumption. The values were not sufficient to explain the clinical symptoms. In contrast, a remarkably strong enrichment of tetradecenoylcarnitine and hexadecenoylcarnitine was observed. This proves a blockade of the long-chain enoyl-CoA hydratase (EC 4.2.1.74). Vertical transfer of maple toxins to a newborn foal is sufficient for induction of clinical disease only if there is an additional specific reactivity to the active toxins. This was found here in an inhibition of long-chain enoyl-CoA hydratase. Isolated dysfunction of this enzyme has not yet been reported in any species. Further studies are necessary to prove a specific genetic defect.

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Section: Discussionmentioning

confidence: 99%

Severe Inhibition of Long-Chain Acyl-CoA Enoylhydratase (EC 4.2.1.74) in a Newborn Foal Suffering From Atypical Myopathy

2021

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“…Growth parameters and developmental assessment have 1.12 page 11 (Shaw, 2020). $ Recommended fat (total, long-chain and medium chain) intake for individuals with VLCAD when well adopted from Van Calcar et al (2020).…”

Section: Case Seriesmentioning

confidence: 99%

“…A LCT restricted diet was introduced at the age of 2 years. The intake of LCT was limited to 20-35% of total energy (Table 1), according to the recommendations (Van Calcar et al, 2020). Dietary requirements for essential fatty acids are being met with walnut oil and docosahexaenoic acid (DHA) supplementation.…”

Section: Case Seriesmentioning

confidence: 99%

“…At the age of 6 months, complementary foods as part of the LCT restricted diet were included. The intake of LCT was limited to 15-30% of total energy intake and at the age of 1 year to 20-30% of total energy intake (Table 1), according to the recommendations (Van Calcar et al, 2020). Dietary requirements for essential fatty acids are being met with walnut oil supplementation.…”

Section: Case Seriesmentioning

confidence: 99%

“…The goals of nutrition therapy are to minimize the production of abnormal fatty acid metabolites with long-chain triglycerides (LCT) restriction and prevention of metabolic crises due to a lack of an adequate energy supply. Nutrition therapy is tailored individually, dependent on the severity of the disorder and patients' age and typically includes restriction of dietary intake of LCT together with supplementation with mediumchain triglycerides (MCT) (Van Calcar et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

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Very Long-Chain Acyl-CoA Dehydrogenase Deficiency: High Incidence of Detected Patients With Expanded Newborn Screening Program

et al. 2021

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Very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) is a rare autosomal recessive disorder of fatty acid metabolism with a variable presentation. The aim of this study was to describe five patients with VLCADD diagnosed through the pilot study and expanded newborn screening (NBS) program that started in 2018 in Slovenia. Four patients were diagnosed through the expanded NBS program with tandem mass spectrometry; one patient was previously diagnosed in a pilot study preceding the NBS implementation. Confirmatory testing consisted of acylcarnitines analysis in dried blood spots, organic acids profiling in urine, genetic analysis of ACADVL gene, and enzyme activity determination in lymphocytes or fibroblasts. Four newborns with specific elevation of acylcarnitines diagnostic for VLCADD and disease-specific acylcarnitines ratios (C14:1, C14, C14:2, C14:1/C2, C14:1/C16) were confirmed with genetic testing: all were compound heterozygotes, two of them had one previously unreported ACDVL gene variant each (NM_000018.3) c.1538C > G; (NP_000009) p.(Ala513Gly) and c.661A > G; p.(Ser221Gly), respectively. In addition, one patient diagnosed in the pilot study also had a specific elevation of acylcarnitines. Subsequent ACDVL genetic analysis confirmed compound heterozygosity. In agreement with the diagnosis, enzyme activity was reduced in five patients tested. In seven other newborns with positive screening results, only single allele variants were found in the ACDVL gene, so the diagnosis was not confirmed. Among these, two variants were novel, c.416T > C and c.1046C > A, respectively (p.Leu139Pro and p.Ala349Glu). In the first 2 years of the expanded NBS program in Slovenia altogether 30,000 newborns were screened. We diagnosed four cases of VLCADD. The estimated VLCADD incidence was 1:7,500 which was much higher than that of the medium-chain acyl-CoA dehydrogenase deficiency (MCADD) cases in the same period. Our study also provided one of the first descriptions of ACADVL variants in Central-Southeastern Europe and reported on 4 novel variants.

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No effect of resveratrol on fatty acid oxidation or exercise capacity in patients with fatty acid oxidation disorders: A randomized clinical cross‐over trial

Storgaard

Løkken

Madsen

et al. 2022

J of Inher Metab Disea

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The objective was to investigate whether resveratrol (RSV) can improve exercise capacity in patients with fatty acid oxidation (FAO) disorders. The study was a randomized, double‐blind, cross‐over trial. Nine patients with very long‐chain acyl‐CoA dehydrogenase (VLCAD) deficiency or carnitine palmitoyl transferase (CPT) II deficiency were randomized to receive either 8 weeks of 1000 mg day−1 RSV or placebo (P) followed by a 4‐weeks wash‐out period and subsequently 8 weeks of the opposite treatment. Primary outcome measures were heart rate and FAO as measured via stable isotope technique during constant workload exercise. Secondary outcome measures included fat and glucose metabolism; perceived exertion; as well as subjective measures of energy expenditure, fatigue, and daily function. Eight participants completed the trial. Heart rate did not differ at the end of exercise after treatment with RSV vs placebo (P = .063). Rate of oxidation of palmitate at end of exercise was not different with 1.5 ± 0.8 (RSV) vs 1.3 ± 0.6 (P) μmol kg−1 min−1 (P = .109). Secondary outcomes did not change except for increased plasma glycerol and decreased plasma glucose levels at the end of exercise after treatment with RSV vs placebo. A daily dose of 1000 mg resveratrol does not improve exercise capacity or FAO during exercise in patients with CPTII or VLCAD deficiencies.

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Nutrition management guideline for very-long chain acyl-CoA dehydrogenase deficiency (VLCAD): An evidence- and consensus-based approach

Cited by 42 publications

References 96 publications

Severe Inhibition of Long-Chain Acyl-CoA Enoylhydratase (EC 4.2.1.74) in a Newborn Foal Suffering From Atypical Myopathy

Severe Inhibition of Long-Chain Acyl-CoA Enoylhydratase (EC 4.2.1.74) in a Newborn Foal Suffering From Atypical Myopathy

Very Long-Chain Acyl-CoA Dehydrogenase Deficiency: High Incidence of Detected Patients With Expanded Newborn Screening Program

No effect of resveratrol on fatty acid oxidation or exercise capacity in patients with fatty acid oxidation disorders: A randomized clinical cross‐over trial

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