Transient multiple acyl-CoA dehydrogenation deficiency in a newborn female caused by maternal riboflavin deficiency

Chiong, Mary Anne D.; Sim, Keow Giak; Carpenter, Kevin; Rhead, William J.; Ho, Gladys; Olsen, Rikke K.J.; Christodoulou, John

doi:10.1016/j.ymgme.2007.06.017

Cited by 42 publications

(37 citation statements)

References 34 publications

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“…This woman was clinically asymptomatic, but showed biochemical evidence of riboflavin deficiency. She was diagnosed after her daughter had presented with poor suck, hypoglycemia, and metabolic acidosis within the first days of life [[45]]. Other riboflavin transporter defects that can mimick mild MADD biochemically are the Brown-Vialetto-Van Laere (BVVL) and the Fazio Londe (FL) syndrome, two disorders which are nowadays considered to be the same disease entity [[44],[46],[47]].…”

Section: Discussionmentioning

confidence: 99%

Clinical and genetical heterogeneity of late-onset multiple acyl-coenzyme A dehydrogenase deficiency

Grünert

2014

Orphanet J Rare Dis

157

156

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BackgroundMultiple acyl-CoA dehydrogenase deficiency (MADD) is an autosomal recessive disorder caused by deficiency of electron transfer flavoprotein or electron transfer flavoprotein dehydrogenase. The clinical picture of late-onset forms is highly variable with symptoms ranging from acute metabolic decompensations to chronic, mainly muscular problems or even asymptomatic cases.MethodsAll 350 cases of late-onset MADD reported in the literature to date have been analyzed and evaluated with respect to age at presentation, diagnostic delay, biochemical features and diagnostic parameters as well as response to treatment.ResultsMean age at onset was 19.2 years. The mean delay between onset of symptoms and diagnosis was 3.9 years. Chronic muscular symptoms were more than twice as common as acute metabolic decompensations (85% versus 33% of patients, respectively). 20% had both acute and chronic symptoms. 5% of patients had died at a mean age of 5.8 years, while 3% of patients have remained asymptomatic until a maximum age of 14 years. Diagnosis may be difficult as a relevant number of patients do not display typical biochemical patterns of urine organic acids and blood acylcarnitines during times of wellbeing. The vast majority of patients carry mutations in the ETFDH gene (93%), while mutations in the ETFA (5%) and ETFB (2%) genes are the exceptions. Almost all patients with late-onset MADD (98%) are clearly responsive to riboflavin.ConclusionsLate-onset MADD is probably an underdiagnosed disease and should be considered in all patients with acute or chronic muscular symptoms or acute metabolic decompensation with hypoglycemia, acidosis, encephalopathy and hepatopathy. This may not only prevent patients from invasive diagnostic procedures such as muscle biopsies, but also help to avoid fatal metabolic decompensations.

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Section: Discussionmentioning

confidence: 99%

Clinical and genetical heterogeneity of late-onset multiple acyl-coenzyme A dehydrogenase deficiency

Grünert

2014

Orphanet J Rare Dis

157

156

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“…Thus, maternal MCADD (Leydiker et al 2011), CTD (De Biase et al 2012;El-Hattab et al 2010;Lee et al 2010;Lund et al 2012;Schimmenti et al 2007;Vijay et al 2006), glutaric acidemia type I (Crombez et al 2008), and combined homocystinuria and methylmalonic aciduria (Lin et al 2009) have all been detected through NBS by the finding of decreased free carnitine in the newborn. In addition, elevated specific acylcarnitines in newborns have revealed maternal 3-methylcrotonyl-CoA carboxylase deficiency (Gibson et al 1998;Koeberl et al 2003;Lund et al 2012), very long-chain acyl-CoA dehydrogenase deficiency (McGoey and Marble 2011), holocarboxylase synthetase deficiency (Nyhan et al 2009), and multiple acyl-CoA dehydrogenation deficiency due to a riboflavin transporter gene defect (Chiong et al 2007;Ho et al 2011). These cases illustrate the importance of taking a detailed maternal history and performing biochemical evaluation with acylcarnitine profile and urine organic acids and when appropriate molecular genetic follow-up in mothers of newborns with abnormal screening results if confirmatory testing shows that the newborn is normal.…”

Section: Discussionmentioning

confidence: 99%

Abnormal Newborn Screening in a Healthy Infant of a Mother with Undiagnosed Medium-Chain Acyl-CoA Dehydrogenase Deficiency

et al. 2015

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A neonate with low blood free carnitine level on newborn tandem mass spectrometry screening was evaluated for possible carnitine transporter defect (CTD). The plasma concentration of free carnitine was marginally reduced, and the concentrations of acylcarnitines (including C6, C8, and C10:1) were normal on confirmatory tests. Organic acids in urine were normal. In addition, none of the frequent Faroese SLC22A5 mutations (p.N32S, c.825-52G>A) which are common in the Danish population were identified. Evaluation of the mother showed low-normal free carnitine, but highly elevated medium-chain acylcarnitines (C6, C8, and C10:1) consistent with medium-chain acyl-CoA dehydrogenase deficiency (MCADD). The diagnosis was confirmed by the finding of homozygous presence of the c.985A>G mutation in ACADM.

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“…It remains unclear whether monocarboxylates are substrates for these transporters. Riboflavin has been suggested as a substrate for MCT12 based on its sequence homology to Mch5p, which is responsible for plasma membrane uptake of riboflavin in Saccharomyces cerevisiae (74). However, functional characterizations of the orphan MCTs have yet to be completed.…”

Section: Orphan Mctsmentioning

confidence: 99%

Overview of the Proton-coupled MCT (SLC16A) Family of Transporters: Characterization, Function and Role in the Transport of the Drug of Abuse γ-Hydroxybutyric Acid

Morris

Felmlee

2008

AAPS J

184

146

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Abstract. The transport of monocarboxylates, such as lactate and pyruvate, is mediated by the SLC16A family of proton-linked membrane transport proteins known as monocarboxylate transporters (MCTs). Fourteen MCT-related genes have been identified in mammals and of these seven MCTs have been functionally characterized. Despite their sequence homology, only MCT1-4 have been demonstrated to be proton-dependent transporters of monocarboxylic acids. MCT6, MCT8 and MCT10 have been demonstrated to transport diuretics, thyroid hormones and aromatic amino acids, respectively. MCT1-4 vary in their regulation, tissue distribution and substrate/inhibitor specificity with MCT1 being the most extensively characterized isoform. Emerging evidence suggests that in addition to endogenous substrates, MCTs are involved in the transport of pharmaceutical agents, including γ-hydroxybuytrate (GHB), 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors (statins), salicylic acid, and bumetanide. MCTs are expressed in a wide range of tissues including the liver, intestine, kidney and brain, and as such they have the potential to impact a number of processes contributing to the disposition of xenobiotic substrates. GHB has been extensively studied as a pharmaceutical substrate of MCTs; the renal clearance of GHB is dose-dependent with saturation of MCT-mediated reabsorption at high doses. Concomitant administration of GHB and L-lactate to rats results in an approximately two-fold increase in GHB renal clearance suggesting that inhibition of MCT1-mediated reabsorption of GHB may be an effective strategy for increasing renal and total GHB elimination in overdose situations. Further studies are required to more clearly define the role of MCTs on drug disposition and the potential for MCTmediated detoxification strategies in GHB overdose.

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Transient multiple acyl-CoA dehydrogenation deficiency in a newborn female caused by maternal riboflavin deficiency

Cited by 42 publications

References 34 publications

Clinical and genetical heterogeneity of late-onset multiple acyl-coenzyme A dehydrogenase deficiency

Clinical and genetical heterogeneity of late-onset multiple acyl-coenzyme A dehydrogenase deficiency

Abnormal Newborn Screening in a Healthy Infant of a Mother with Undiagnosed Medium-Chain Acyl-CoA Dehydrogenase Deficiency

Overview of the Proton-coupled MCT (SLC16A) Family of Transporters: Characterization, Function and Role in the Transport of the Drug of Abuse γ-Hydroxybutyric Acid

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