E Simon1, N Flaschker, P Schadewaldt, U Langenbeck, U Wendel. 1. Department of General Paediatrics, University Children's Hospital, Heinrich-Heine University, Moorenstr. 5, D-40225, Düsseldorf, Germany. simon@med.uni-duesseldorf.de
Abstract
BACKGROUND: In the rare inborn autosomal recessive disorder maple syrup urine disease (MSUD) the accumulation of the branched-chain amino acids (BCAAs) and their metabolic products results in acute and chronic brain dysfunction. About 20% of the patients suffer from non-classic variant forms of MSUD of different clinical severity. AIM: Up to now variant cases have mostly been published as individual case reports; the aim of this study was to give a comparative description of 16 individuals (aged 6-30 years) with different forms of variant MSUD. METHODS: Laboratory data, information on clinical course and treatment as well as aspects of developmental, intellectual and social outcome were obtained retrospectively. Data from in vitro and in vivo methods measuring the degree of enzyme deficiency were included. RESULTS: In addition to a mild phenotype, which fits well into the so-called intermittent variant, and a more severe phenotype with a wider range from a mild variant to an almost classic form, which fits well into the so-called intermediate variant, we assume the existence of an asymptomatic, non-disease variant of MSUD. These clinical phenotypes are not unambiguously differentiable on the basis of biochemical parameters. CONCLUSION: A continuum of clinical severity from asymptomatic to very severe (border to classic) exists in variant MSUD. Apart from newborns with classic MSUD, also those with variant forms benefit from early diagnosis and start of adequate treatment.
BACKGROUND: In the rare inborn autosomal recessive disorder maple syrup urine disease (MSUD) the accumulation of the branched-chain amino acids (BCAAs) and their metabolic products results in acute and chronic brain dysfunction. About 20% of the patients suffer from non-classic variant forms of MSUD of different clinical severity. AIM: Up to now variant cases have mostly been published as individual case reports; the aim of this study was to give a comparative description of 16 individuals (aged 6-30 years) with different forms of variant MSUD. METHODS: Laboratory data, information on clinical course and treatment as well as aspects of developmental, intellectual and social outcome were obtained retrospectively. Data from in vitro and in vivo methods measuring the degree of enzyme deficiency were included. RESULTS: In addition to a mild phenotype, which fits well into the so-called intermittent variant, and a more severe phenotype with a wider range from a mild variant to an almost classic form, which fits well into the so-called intermediate variant, we assume the existence of an asymptomatic, non-disease variant of MSUD. These clinical phenotypes are not unambiguously differentiable on the basis of biochemical parameters. CONCLUSION: A continuum of clinical severity from asymptomatic to very severe (border to classic) exists in variant MSUD. Apart from newborns with classic MSUD, also those with variant forms benefit from early diagnosis and start of adequate treatment.
Authors: George V Mazariegos; D Holmes Morton; Rakesh Sindhi; Kyle Soltys; Navdeep Nayyar; Geoffrey Bond; Diana Shellmer; Benjamin Shneider; Jerry Vockley; Kevin A Strauss Journal: J Pediatr Date: 2011-08-11 Impact factor: 4.406
Authors: H A Jinnah; Alberto Albanese; Kailash P Bhatia; Francisco Cardoso; Gustavo Da Prat; Tom J de Koning; Alberto J Espay; Victor Fung; Pedro J Garcia-Ruiz; Oscar Gershanik; Joseph Jankovic; Ryuji Kaji; Katya Kotschet; Connie Marras; Janis M Miyasaki; Francesca Morgante; Alexander Munchau; Pramod Kumar Pal; Maria C Rodriguez Oroz; Mayela Rodríguez-Violante; Ludger Schöls; Maria Stamelou; Marina Tijssen; Claudia Uribe Roca; Andres de la Cerda; Emilia M Gatto Journal: Mov Disord Date: 2017-09-01 Impact factor: 10.338
Authors: João Leandro; Sara Violante; Carmen A Argmann; Jacob Hagen; Tetyana Dodatko; Aaron Bender; Wei Zhang; Evan G Williams; Alexis M Bachmann; Johan Auwerx; Chunli Yu; Sander M Houten Journal: Mol Genet Metab Date: 2019-01-24 Impact factor: 4.797