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Challenges in long-term management of MSUD: a prospective study by assessment of clinical, Biochamical and Anthropometric Parameters

Investigador: Sandra Mexia
Instituição: Centro Hospitalar de Lisboa Norte, Hospital de Santa Maria


Maple syrup utine disease (MSUD - OMIM # 24860) is a rare unherited sidorder of branched-chain amino acids (BCAAs) - leucine (Leu), isoleucine (lLe) and valine (Val), displaying an autosomal recessive pattern of inheritance, and caused by deficiency of branched-chain aketo acid dehydrogenase, the enzymatic complex responsible for the breaking down of byproducts of the BCAAs transmination reactioin, the corresponding branched-chain a-keto-acids (BCKA).

The disruption of this metabolic pathway results in the accumulation of BCAAs and BCKA in cells and fluis of the body, which present neurotoxic, especially Leu and the corresponding a-keto-acid, the a-keto-isocaproic acid (KIC). To avoid life-threatening complications, treatment must promptly be strated. MSUD's treatment, primarily nutritional, is based on manipulation of a restricted natural protein diet with reduced BCAAs content and supplementation eith synthetic formulas for the supplying of essential amino acids and micronutrients, pivotal for ensuring normal grosth and psychomotor development of effected children.
Manipulation of dietary therapy is an ongoing challenge, requiring constant adjustments based on biochemical parameters, namely BCAAS blood levels, and clinical manifestations.
Furthermore, catabolism must be avoided and anabolism promoted in order to avoid episodes of acute illness triggered by exogenous injuries. In Portugal, and dating back to 2007, a National Consensus, based on the literature and on the daily treatment practice, is being used as support for treatment orientations. Recently, in 2014, Dianne Fraizer and collaborators (Frazier, 2014) published guidelines for the nutritional management of MSUD. New cut-off values for BCAAs plasma concentrations are suggested, as well as recommendations regarding the manipulation of protein and dietary supplements. A prospective studied, enrolling 12 MSUD patients under treatment in our metabolic unit, is here proposed to assess the efficacy of the recently published guidelines when compared wirh the current treatment, assuming that the introduction of the proposed alterations for the protein and dietary supplements, along with the new recommended BCAAs plasma levels, will allow an improvement in MSUD patients metabolic control and, therefore, in their outcome. Furthermore, the impact of these guidelines on several biomarkers sill be evaluated, paying special attention to those involved in oxidative stress and mitochondrial dysfunction. All variables will be analyzes using suitable statistical programs. Based on the achieved data the ANtional consensus will be reviewed and the new version will be submitted for approval by the representatives of National Reference Centers for IEM



Faculdade de Farmácia da U.L.
Av. Prof. Gama Pinto
1649-003 Lisboa

Contacto: Fernanda Asper
Telefone.: +351 217 946 400
Fax: +351 217 946 491


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