Maple Syrup Urine Disease

Abstract

More than 20 instances of maple syrup urine disease (MSUD) have been described since 1954. Most were infants, who manifested in the first month of life a maple syrup odor in their urine and a clinical pattern of fits, episodic rigidity, lethargy, and poor suck. When measured, their blood and urine levels were found to be elevated for the branched-chain amino acids (valine, leucine, and isoleucine) and the \g=a\-keto-acids derived from them.Our purpose is to record the family pedigree of another infant with MSUD and to Family Pedigree In 1959, Lane reported on an infant (X in Fig 1) seen in this hospital with MSUD.She mentioned that a sister and a cousin of her patient had died at ten days of age with clinical findings which were highly suggestive of that disease.1 Subsequent family studies have added a number of facts. Consanguinity was established for the parents of her patient. An eight-year-old sister, al¬ though mentally retarded and subject to grand mal seizures, has a normal pattern of plasma and urine amino and a-keto-acids. So has a later sister, neurologically normal at age three. No significant alterations in blood and urine levels of these substances have been provoked in either child after oral loading with L-valine, L-leucine, and L-isoleucine.Y, the subject of this report, was born in 1962. Her father, at 22 years, has been treated for agitated depression. He is related to the 20-year-old mother, and both parents share a common ancestor with the parents of X. Blood and urine patterns for branchedchain amino acids and a-keto-acids are nor¬ mal in both sets of parents. These patterns were not altered significantly by oral loads of L-valine and L-leucine.Normal levels of branched-chain amino and a-keto-acids also were found in the urine of a number of related persons (Figi).Using branched-chain keto-aciduria to de¬ fine the disease, this pedigree suggests in¬ heritance through an autosomal recessive gene. Clinical and biochemical observations have failed to indicate a dependable clue for determining heterozygosity. Report of a CaseHistory.-With this family background, it was not surprising that Y was admitted with clinical findings of MSUD. After an uncomplicated pregnancy and delivery, she had seemed normal at birth and remained so for five days. She then rapidly developed lethargy, inability to suck, and Downloaded From: http://archpedi.jamanetwork.com/ by a University of Iowa User on 06/07/2015

Idiopathic Hypervalinemia

“…Maple sugar urine disease, first described by Menkes et al2), is now known to be an inborn error of the branched chain amino acids-leucine, isoleucine and valine3,10). Clinical features of maple sugar urine disease were vomiting, difficulty in feeding, muscular hypertonicity, flaccidity, convulsion, failure to growth and a peculiar odor of urine resembling that of maple sugar1, 2,3,11) As regards clinical symptoms there may be many similarities between our own case and the cases with maple sugar urine disease. But in detail some differences exist between them.…”

A case of hyperlysinemia identified by urine newborn screening

“…Several early case reports have associated hyperlysinemia with developmental delay, intellectual disability, and muscle weakness through screening of affected (institutionalized) children for abnormal plasma amino acids. 11,12 A followup study, however, questioned a causal relationship because healthy hyperlysinemic family members were also identified. 13 Since then, other reports have been consistent with a benign nature of hyperlysinemia.…”