Clues and challenges in the diagnosis of intermittent maple syrup urine disease

European Journal of Medical Genetics
Naomi Pode-ShakkedYair Anikster

Abstract

Maple syrup urine disease is a rare autosomal-recessive aminoacidopathy, caused by deficient branched-chain 2-keto acid dehydrogenase (BCKD), with subsequent accumulation of branched-chain amino acids (BCAAs): leucine, isoleucine and valine. While most cases of MSUD are classic, some 20% of cases are non-classic variants, designated as intermediate- or intermittent-types. Patients with the latter form usually develop normally and are cognitively intact, with normal BCAA levels when asymptomatic. However, intercurrent febrile illness and catabolism may cause metabolic derailment with life-threatening neurological sequelae. Thus, early detection and dietary intervention are warranted in intermittent MSUD. We describe eight patients from four unrelated families, diagnosed with intermittent MSUD. Their presenting symptoms during metabolic crises varied from confusion and decreased consciousness, to ataxia, and acute psychosis. Molecular confirmation of MSUD was pursued via sequencing of the BCKDHA, BCKDHB and DBT genes. All affected individuals were found to harbor bi-allelic pathogenic variants in either BCKDHB or DBT. Of the seven variants, four variants in BCKDHB (p.G101D, p. V103A, p. A221D, p. Y195C) and one variant in DBT (p....Continue Reading

Citations

May 24, 2020·International Journal of Molecular Sciences·Giacomo GaroneFrancesco Nicita
Aug 6, 2020·International Journal of Molecular Sciences·Grace Silver, Saadet Mercimek-Andrews
Oct 15, 2020·International Journal of Molecular Sciences·Jing XuRebecca C Ahrens-Nicklas
May 7, 2021·Molecular Genetics & Genomic Medicine·Diana Ruffato Resende CampanholiJosé S Camelo
Jun 29, 2021·Frontiers in Neurology·Susan HarveyKathleen M Gorman

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