Maple Syrup Urine Disease, With Particular Reference to Dietotherapy

Abstract

1. Our experiences with 7 patients with maple syrup urine disease are described. 2. It has been shown that the abnormal biochemistry and the neurological manifestations of maple syrup urine disease can be controlled by a diet low in the branched chain amino acids—leucine, isoleucine, and valine. If control is instituted sufficiently early, there is evidence that mental defect can be prevented. 3. A fourth abnormal amino acid, formerly thought to be methionine, has now been identified as alloisoieucine and evidence has been obtained that this is formed from isoleucine. Indications for restricting the methionine intake no longer exist. 4. Some of the hazards of dietotherapy in this disease are discussed, among them the existence of an unknown nutritional factor which is deficient in synthetic diets containing all the known dietary essentials. 5. The limitations of exchange transfusion for the immediate initial therapy of the disease are pointed out.

Mutual influences of substrates on bovine α-keto acid metabolism

“…The major thrust of initial studies of the metabolism of the branched-chain amino acids centered upon the characterization of the overall degradative pathways of leucine, isoleucine, and valine (Coon et al, 1955); elucidation of the site of the catabolism of these compounds in the genetic disease branched-chain ketoaciduria (Dancis et al, 1963;Dancis and Levitz, 1966;Dancis, 1957), and development of therapeutic dietary treatment designed to control the symptoms of the disease (Westall, 1963;Snyderman et al, 1964). Recently, however, there has been a growing awareness of the complexity and multiplicity of the regulatory mechanisms which 8.6 X "4 2.5 X 10-4 2.3 X IO-3 1.4 X IO-3 l-12C-Labeled KIC 6.9 X 10~4 1.3 X IO"4 5.4 X IO"4 2.4 X IO"3 l-12C-Labeled KIV l-12C-Labeled KV 2.2 X KC4…”

“…Although the exact cause of the neurological pathology commonly associated with branched-chain ketoaciduria is not known, a correlation between the neurologic symptoms and elevated leucine and KIC has been established (Snyderman et al, 1964). The results of the mutual inhibition studies (Table II) disclose that KIC among the three branched-chain 3 Since the inhibition of pyruvate oxidation by KIC is of the competitive type, eq 1 is applicable for the calculation of the inhibitor constants, Ki.…”

Mutations in BCKD-kinase Lead to a Potentially Treatable Form of Autism with Epilepsy

“…2E). Mutations in any of the three subunits of the BCKDH complex lead to toxic accumulation of BCAAs and their metabolites and are the cause of maple syrup urine disease (7), characterized by severe neurological complications and treated by dietary restriction of BCAAs, which are essential amino acids (8). BCKDK is expressed widely in mouse and human tissues (fig.…”

“…tructured RNAs function during transcription or translation to influence a variety of processes. In vivo, nascent RNAs fold as they are transcribed, and this sequential process affects the folding efficiency (1-4) and the predominant conformation (5)(6)(7)(8)(9). The study of cotranscriptional folding has heretofore been largely indirect, with most approaches monitoring the final RNA product (1-10).…”

‘Chemical co-substrate rescue’ of phytanoyl-CoA 2-hydroxylase mutants causing Refsum’s Disease

“…Maple syrup urine disease is caused by a deleterious accumulation of excess 2-oxacids, and is treated, in the reverse of this proposed therapy, by a diet low in branched-chain amino acids. 13 Restoration of complete wild-type activity may not be required, as 5% of wild-type activity is apparently sufficient to effectively correct inherited homocystinuria 14 with vitamin B6.…”