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  • Updated 08.13.2021
  • Released 12.28.1993
  • Expires For CME 08.13.2024

Maple syrup urine disease

Introduction

Overview

Maple syrup urine disease is an inborn error of branched-chain ketoacid metabolism that presents classically with metabolic distress in newborns, although milder presentations exist. Branched-chain amino acids (leucine, isoleucine, and valine) and their ketoacids are increased in the blood, and the intake of these amino acids must be controlled. In this article, the authors detail novel approaches to the treatment of maple syrup urine disease, such as the experimental use of phenylbutyrate to prevent the inactivation of the implicated dehydrogenase complex.

Key points

• Inborn errors of metabolism should be suspected in newborns and infants with unexplained encephalopathies.

• Soon after birth, maple syrup urine disease classically presents with an encephalopathy accompanied by abnormal movements such as pedaling, ketonuria, and urine with a burnt sugar odor.

• The metabolic defect is in the branched-chain keto acid dehydrogenase complex, and dietary branched-chain amino acids (leucine, isoleucine, and valine) should be restricted and monitored.

• Novel therapies investigated include hepatocyte transplantation, drugs to counter oxidative stress, norleucine, and phenylbutyrate to prevent the inactivation of the dehydrogenase complex.

Historical note and terminology

A hereditary encephalopathy with sweet-smelling urine was described in 1954 (53), and shortly thereafter elevations in plasma branched-chain amino acids and their keto acids in the urine were noted (96; 52). A defect in branched-chain alpha-ketoacid dehydrogenase was then identified (22). Dietary therapy was established, and newborn screening programs were implemented (97; 85). The genes encoding the proteins that form the complex were subsequently identified.

Component

Subunit

Mutations

in MSUD

MSUD

type

Gene

Reference for cloning or identification

Branched-chain alpha-ketoacid decarboxylase

E1-alpha

Yes

IA

BCKDHA

(92)

Branched-chain alpha-ketoacid decarboxylase

E1-beta

Yes

IB

BCKDHB

(59)

Branched-chain dihydrolipoamide acyltransferase

E2

Yes

II

DBT

(23; 24)

Dihydrolipoamide dehydrogenase

E3

Yes

III

DLD

(61)

BCKD kinase

No

N/A

BCKDK

(66)

BCKD phosphatase

Yes

N/A

PPM1K

(62)

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