In this report, we describe the case of an 11-year-old boy, who came to ourattention for myalgia and muscle weakness, associated with inappetence andvomiting. Hypertransaminasemia was also noted, with ultrasound evidence ofhepatomegaly. Biochemical investigations revealed acylcarnitine and organicacid profiles resembling those seen in MADD, that is, multiple acyl-CoA dehy-drogenase deficiencies (OMIM #231680) a rare inherited disorder of fatty acids,amino acids, and choline metabolism. The patient carried a single pathoge-netic variant in theETFDHgene (c.524G>A, p.Arg175His) and no pathoge-netic variant in the riboflavin (Rf) homeostasis related genes (SLC52A1,SLC52A2,SLC52A3,SLC25A32,FLAD1). Instead, compound heterozygosity wasfound in theACAD8gene (c.512C>G, p.Ser171Cys; c.822C>A, p.Asn274Lys),coding for isobutyryl-CoA dehydrogenase (IBD), whose pathogenic variantsare associated to IBD deficiency (OMIM #611283), a rare autosomal recessivedisorder of valine catabolism. The c.822C>A was never previously describedin a patient. Subsequent further analyses of Rf homeostasis showed reducedlevels of flavins in plasma and altered FAD-dependent enzymatic activities inerythrocytes, as well as a significant reduction in the level of the plasma mem-brane Rf transporter 2 in erythrocytes. The observed Rf/flavin scarcity in thispatient, possibly associated with a decreased ETF:QO efficiency might beresponsible for the observed MADD-like phenotype. The patient's clinical pic-ture improved after supplementation of Rf,L-carnitine, Coenzyme Q10, andalso 3OH-butyrate. This report demonstrates that, even in the absence ofgenetic defects in genes involved in Rf homeostasis, further targeted molecu-lar analysis may reveal secondary and possibly treatable biochemical alter-ations in this pattern.

Combined isobutyryl‐CoA and multiple acyl‐CoA dehydrogenase deficiency in a boy with altered riboflavin homeostasis

Tummolo, Albina;Leone, Piero;Tolomeo, Maria;Solito, Rita;Barile, Maria
2022

Abstract

In this report, we describe the case of an 11-year-old boy, who came to ourattention for myalgia and muscle weakness, associated with inappetence andvomiting. Hypertransaminasemia was also noted, with ultrasound evidence ofhepatomegaly. Biochemical investigations revealed acylcarnitine and organicacid profiles resembling those seen in MADD, that is, multiple acyl-CoA dehy-drogenase deficiencies (OMIM #231680) a rare inherited disorder of fatty acids,amino acids, and choline metabolism. The patient carried a single pathoge-netic variant in theETFDHgene (c.524G>A, p.Arg175His) and no pathoge-netic variant in the riboflavin (Rf) homeostasis related genes (SLC52A1,SLC52A2,SLC52A3,SLC25A32,FLAD1). Instead, compound heterozygosity wasfound in theACAD8gene (c.512C>G, p.Ser171Cys; c.822C>A, p.Asn274Lys),coding for isobutyryl-CoA dehydrogenase (IBD), whose pathogenic variantsare associated to IBD deficiency (OMIM #611283), a rare autosomal recessivedisorder of valine catabolism. The c.822C>A was never previously describedin a patient. Subsequent further analyses of Rf homeostasis showed reducedlevels of flavins in plasma and altered FAD-dependent enzymatic activities inerythrocytes, as well as a significant reduction in the level of the plasma mem-brane Rf transporter 2 in erythrocytes. The observed Rf/flavin scarcity in thispatient, possibly associated with a decreased ETF:QO efficiency might beresponsible for the observed MADD-like phenotype. The patient's clinical pic-ture improved after supplementation of Rf,L-carnitine, Coenzyme Q10, andalso 3OH-butyrate. This report demonstrates that, even in the absence ofgenetic defects in genes involved in Rf homeostasis, further targeted molecu-lar analysis may reveal secondary and possibly treatable biochemical alter-ations in this pattern.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11586/403631
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