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Screening & Prevention >> Newborn Screening >> Amino Acid Disorders >> Maple syrup urine disease

Maple syrup urine disease

Disorder Category

an amino acid (urea cycle) disorder

Screening

Finding

elevated leucine and leucine/alanine ratio

Tested By

tandem mass spectrometry (MS/MS); sensitivity=100%; specificity=99.99% [Schulze: 2003]

Names

Maple syrup urine disease

Branched-chain ketoaciduria

Branched-chain ketoacid dehydrogenase deficiency (BCKD)

ICD-9

270.3, Disturbance of branched-chain amino-acid metabolism

Overview

Result of a defect in branched-chain ketoacid dehydrogenase (BCKD), a multienzyme complex with 3 components found in mitochondria in liver, kidney, leukocytes and fibroblasts. The enyzme is responsible for the synthesis of oxoacids. Accumulation of leucine and its corresponding BCKA, alpha-ketoisocaproic acid (alpha KIC), disturbs brain cell volume regulation with consequent brain edema, neuron growth, myelin synthesis, and cerebral neurotransmitters.

Prevalence

estimates include 1/185,000 [Maple Syrup Urine Disease review, GeneTests.org], 1/200,000 [Maple Syrup Urine Disease info for professionals, STAR-G], and 1/250,000 live births [Schulze: 2003]; incidence in the Old Order Mennonite population is between 1/358 [Maple Syrup Urine Disease review, GeneTests.org] and 1/760 [Maple Syrup Urine Disease info for professionals, STAR-G].

Inheritance

autosomal recessive

Prenatal Testing

DNA testing or enzyme analysis by amniocentesis or CVS.

Other Testing

DNA testing may be possible if the mutation is known.

Clinical Characteristics

With treatment before crises, normal IQ and development can be expected. Without treatment, one can expect profound mental retardation and neurologic disturbances. Brain edema can lead to cerebellar herniation, compression of the brain stem, and death, especially in older individuals.

Initial symptoms, beginning with protein ingestion, may include:
  • a maple syrup odor of cerumen, usually by 12-24 hours of age;
    • elevated branched-chain amino acids, leucine, isoleucine, and valine are detectable by this time;
  • irritability, poor feeding, and vomiting within 2-3 days;
    • ketonuria is now present;


By 4-5 days, symptoms include:
  • lethargy;
  • intermittent apnea;
  • arching; and
  • repetitive "fencing" or "bicycling" movements;


Followed within another 3-5 days by:
  • coma and central respiratory failure.


Because of the rapidity of onset, severe symptoms may be present before screening results are reported or treatment begins.

Variant forms of the disease may have milder and later onset of symptoms, presenting with anorexia, poor growth, irritability, or developmental delay in late infancy or childhood. Symptoms and metabolic crisis episodes may be precipitated by illnesses. Urine may also have a maple syrup odor, especially during metabolic crisis. One variant is responsive to thiamine.

Follow-up on positive screening test

Plasma amino acids (elevated leucine, isoleucine, alloleucine, valine); urine organic acid analysis (abnormal branched-chain hydroxyl- and ketoacids); hyperalimentation may cause abnormal results.

Primary care management

Upon notification of the + screen

If the diagnosis is confirmed

  • Educate the family regarding signs, symptoms, and the need for urgent care when the infant becomes ill (see Maple Syrup Urine Disease info for parents, STAR-G);
  • Support initiation and maintenance of dietary restriction of branched-chain amino acids (found in animal and vegetable food sources), use of medical formulas; providing protein as essential and non-essential amino acids; and supplementation with isoleucine or valine as needed;
  • Thiamine may be indicated for children with the thiamine-responsive variant;
  • See patients readily when illness occurs, since that is the primary cause of decompensation; monitoring of urinary BCKA excretion with DNPH reagent strips at home; measuring amino acid levels through blood tests when indicated;
  • For any decompensation that does not promptly respond to outpatient treatment, admit to the hospital and seek expert assistance for management;
  • For those identified after irreversible consequences, assist in management, particularly with developmental and educational interventions.

Specialty Care Management

Initial consultation and ongoing collaboration, particularly for dietary management and management of decompensation episodes. Genetic counseling for the family. Liver transplantation can be effective therapy allowing unrestricted diet and possibly preventing neurologic deterioration.

Resources

Links

For Professionals

Maple Syrup Urine Disease info for professionals, STAR-G
On the Screening, Technology and Research in Genetics (STAR-G) site, one of a series of Disorder Fact Sheets for Professionals; structured list of information about the condition, with links to more information.

ACT Sheet for Maple Syrup Urine Disease from ACMG (pdf 251kb)
Developed by the American College of Medical Genetics (ACMG), includes recommended responses to positive newborn screening test results, diagnostic evaluation, clinical expectations, and sources of additional information. See the ACMG ACT Sheets and Confirmatory Algorithms (link elsewhere on this page) for more info and sheets on other conditions.

ACMG ACT Sheets and Confirmatory Algorithms
The American College of Medical Genetics (ACMG) has developed ACTion (ACT) Sheets and algorithms for responding to positive newborn screening test results. This page contains a table with links to all of the ACT Sheets and related algorithms.

Maple Syrup Urine Disease review, GeneTests.org
Excellent review by Kevin A. Strauss, MD, Erik G. Puffenberber, MD and D. Holmes Morton, MD including clinical description, differential, management, genetic counseling, molecular genetics, and a bibliography.

Maple Syrup Urine Disease Emergency Protocol
A protocol for management of the patient with a positive screen for Maple Syrup Urine Disease, from the New England Consortium of Metabolic Programs.

Utah Newborn Screening Program
The site provides information and statistics about the program and related legislation, training for practices, and the conditions screened for.

For Parents

Maple Syrup Urine Disease info for parents, STAR-G
From the Screening, Technology and Research in Genetics (STAR-G) site, providing information for parents about Maple Syrup Urine Disease and links to other sites including parent support groups.

Maple Syrup Urine Disease Family Support Group
The Maple Syrup Urine Disease Support Group, a non-profit organization, provides information for parents and the public; newsletters and articles; event information; family stories; support services for families; recipe and formula information; dietary resources; and links to other sites.

Maple Syrup Urine Disease, Genetics Home Reference
Excellent, detailed review aimed at patients and families from the National Library of Medicine's Genetics Home Reference site.

Services

Newborn Screening Programs

Utah Newborn Screening Program, more info...
44 Mario Capecchi Drive
Salt Lake City, UT84114
Phone: 801-584-8256
Fax: 801-536-0966
http://health.utah.gov/newbornscreening

Pediatric Genetics

Metabolic Clinic, more info...
100 Mario Capecchi Drive
Salt Lake City, UT84113
Phone: 801-585-2457
Fax: 585-7252
http://www.ped.med.utah.edu/divisions/divisions.htm

See all Pediatric Genetics services providers (3) in our database.

For other services related to this condition, browse our Services categories or search our database.

Helpful Articles

PubMed search for articles on Maple Syrup Urine Disease in the last 5 years.

Authors

Reviewing Author: Nicola Longo MD, PhD, 3/2007
Compiled and edited by: Alfred Romeo RN, PhD, 3/2007
Content Last Updated: 3/2008

Page Bibliography

Schulze A, Lindner M, Kohlmuller D, Olgemoller K, Mayatepek E, Hoffmann GF.
Expanded newborn screening for inborn errors of metabolism by electrospray ionization-tandem mass spectrometry: results, outcome, and implications.
Pediatrics. 2003;111(6 Pt 1):1399-406. PubMed abstract
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