The Therapy of Maple Syrup Urine Disease

Abstract

BOTH THE clinical picture and the metabolic abnormality in maple urine disease pose special problems in its management. The rapid progression of symptoms (from feeding problems and apathy to the onset of central nervous system signs with periods of hypertonicity alternating with hypotonia, loss of Moro's reflex, difficulties with respiration to convulsions and death) makes prompt and proper treatment imperative. The nature of the defect, involving three essential amino acids, triples the problems of dietary management. In the seven years since treatment of the first case was initiated,1 our group at New York University has been able to develop a fairly well-defined schedule for initiating and continuing therapy.The metabolic defect is the failure of oxidative decarboxylation of the keto-acid derivatives of the branched chain amino acids (Fig 1). This results in the accumulation of these compounds as well as of the branched chain amino acids (leucine, isoleucine, and valine) in the plasma, red blood cells, urine, and cerebrospinal fluid. The aim of therapy, to bring these levels back to nor¬ mal as rapidly as possible, has been accom¬ plished by the use of a completely synthetic diet, the protein moiety of which is a mix¬ ture of L-amino acids (Table 1). Treatment is instituted with complete omission of the branched chain-amino acids while the plasma amino acids are monitored frequently, every two or three days. As the level of each branched chain amino acid returns to normal, supplementation with that amino acid in the form of a pure solution is started. We prefer the use of the amino acid at this point to a natural food such as milk in order to provide the exact requirement of each amino acid rather than the fixed ratio present in food. After the plasma levels have become more stable, small quantities of milk are used to provide the necessary amounts of the Table 1.-Composition of the Synthetic Diet Component Amount (gm) Percentage of Total Calories L-amino acid mixture L-alanine

Biochemical Observations on So-called Hereditary Tyrosinemia

“…The tyrosyluria was unresponsive to ascorbic acid (275 mg/24 h orally for 3 days), folic acid (5 mg/24 h given intramuscularly for 3 days), and a low protein diet (1.5 g/kg/24 h for 4 days). At 11 weeks of age she was started on a low methionine diet, based on the Snyderman regimen [27]. At this time, an intravenous pyelogram showed enlarged kidneys, and X-ray of long bones showed demineralization, but no rachitic changes.…”

Maple syrup urine disease: Clinical outcomes, metabolic control, and genotypes in a screened population after four decades of newborn bloodspot screening in the Republic of Ireland

“…Maple syrup urine disease (MSUD, OMIM 248600) is a rare, inborn metabolic disorder which arises from a profound defect in the catabolic pathways of the branched‐chain amino acids (BCAA) leucine, isoleucine, and valine 1,2 . It is associated with elevated body fluid levels of the BCAA, especially leucine.…”

Maple Syrup Urine Disease

“…A review of thirty fullydescribed cases of MSUD from the literature is detailed in Table I1 (Menkes et a/. 1954, Lonsdale et al 1963, Morris et al 1961, Dancis et al 1967, Woody et al 1963, Smith and Strang 1958, Linneweh and Solcher 1965, MacKenzie and Woolf 1959, Goedde et al 1966, Snyderman et al 1964, Snyderman 1967, Lane 1961, Sander et al 1968).…”