Evaluation of branched‐chain amino acid intake in children with maple syrup urine disease and methylmalonic aciduria

Abstract

The biochemical and growth responses to dietary branched-chain amino acid (BCAA) intake were studied in two children; one with a disorder of branched-chain amino acid metabolism, maple syrup urine disease (MSUD) (McKusick 24860), and another with methylmalonic aciduria (MMA) (McKusick 25100). Biochemical control of MSUD focussed on plasma leucine levels while measurement of plasma ammonia levels was used in MMA. From 0 to 2.75 years both patients exhibited five episodes of toxicity. In each case toxicity was associated with dietary indiscretion or infection. The quantity of protein tolerated was always less in the MMA patient and was approximately 1 g/kg/day. From 1 to 2.75 years each patient's growth velocity approximated their predicted growth channel except during periods of toxicity. In both cases leucine intake, which gave normal growth without toxicity, was always judged to be less than the FAO/WHO recommendations. The BCAA intake of the MMA patient was remarkably stable from 0.5 to 2.75 years and at 2 years of age isoleucine and valine intake approximated the FAO/WHO recommendations. From 2 to 2.75 years BCAA intake (mg/kg/day) of the MSUD patient was less than that of the MMA patient and well below FAO/WHO recommendations. Neuromotor development in both patients is normal.

A critical reappraisal of dietary practices in methylmalonic acidemia raises concerns about the safety of medical foods. Part 1: isolated methylmalonic acidemias

“…Surprisingly, the complete protein intake and individual essential BCAA intake consumed by patients in our study were higher than the recommended amounts for other inborn errors, like phenylketonuria (PKU) or maple syrup urine disease (MSUD) 1 , 4 , 26 , where protein restriction is an essential part of their management, and higher than the FAO/WHO/UNU (2007) safe protein intake levels 5 proposed in the European guidelines or metabolic textbooks for MMA ( Table 2 ). It has been argued that RDA is inadequate in organic acidemias because 1) most of the dietary protein is plant-derived, which may not contain complementary AA’s or can be less digestible; 2) complete protein when given as free AA formula (Splash, Neocate, Elecare, etc) should be increased by about 20% to account for altered absorption and oxidation rates; 3) patients have frequent catabolic episodes resulting in need for catch up growth 1 .…”

Management of a case of maple syrup urine disease - the use of gluco-insulinotherapy

“…O prognóstico dos portadores da MSUD tem mudado nitidamente nos últimos 10 anos, no Primeiro Mundo, em decorrência do aperfeiçoamento dos programas de triagem neonatal, do diagnóstico e do manejo terapêutico dessa doença 1,5,11,12,13 . Danner e Elsas (1989), por exemplo, compararam seus casos diagnosticados até 1980 com os diagnosticados a partir desse ano e demonstraram que de lá para cá não só não houve mortes entre os 10 últimos casos por eles tratados, como também o QI alcançado foi superior a 90 pontos em 7 dos 10 pacientes.…”

Application of Metabolomic Principles to Disorders of Nucleotide Metabolism Reveals New Metabolic Perturbations

“…[2,3] Plasma amino acids were quantitated using the Biochrom 20 or 30 amino acid analyzers with ninhydrin derivatisation, using physiological amino acid standards (Sigma-Aldrich, Canada) and S-(2-aminoethyl)-L-cysteine as internal standard. [4,5] Plasma methylmalonic acid was analyzed on a HewlettPackard GC-MS, using methyl-d3-malonic acid as an internal standard (CDN Isotopes, Canada). [6] …”