Home > Newborn Disorders > Maple syrup urine disease
Maple syrup urine disease
Screening
Tested By
tandem mass spectrometry (MS/MS); sensitivity=100%; specificity=99.99%. [Schulze: 2003] Note that milder forms of the disease can be missed by newborn screening. [Puckett: 2010]Names
Maple syrup urine disease
Branched-chain ketoaciduria
Branched-chain ketoacid dehydrogenase (BCKD) deficiency
Overview
Caused by a defect in branched-chain ketoacid dehydrogenase (BCKD), a multienzyme complex with 4 components found in mitochondria in liver, kidney, muscle, and fibroblasts. The enyzme is responsible for the degradation of oxoacids. Accumulation of leucine and its corresponding branched-chain keto acid (BCKA), alpha-ketoisocaproic acid (alpha KIC), disturbs brain cell volume regulation with consequent brain edema and secondary impairment of neuron growth, myelin synthesis, and cerebral neurotransmitter production. These can cause death, mental retardation, and disability..Prevalence
estimates include 1/225,000 [Carleton: 2010]; incidence in the Old Order Mennonite population is about 1/150 liver births. [Carleton: 2010]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, can be present by 12-24 hours of age
- elevated branched-chain amino acids, leucine, isoleucine, and valine and presence of allo-isoleucine detectable shortly after birth, but can be missed by the newborn screening if the sample is obtained too early (<12h after birth) or in milder forms of the disease
- ketonuria becomes evident after branched-chain amino acids become elevated
- irritabililty, poor feeding, and vomiting
- lethargy
- intermittent apnea
- arching
- repetitive "fencing" or "bicycling" movements
- coma and central respiratory failure
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. Hydroxyprolinemia, a benign condition, can cause abnormal newborn screening for maple syrup urine disease, since hydroxyproline has the same mass/charge ratio of leucine/isoleucine.Primary care management
Upon notification of the + screen
- Contact the family and evaluate the infant for poor feeding, lethargy, irregular breathing pattern;
- Provide emergency treatment/referral for lethargy, tachypnea, alternating hypertonia/hypotonia, or seizures (see ACT sheet for maple syrup urine disease
(
369 KB)
for additional information);
- Discontinue breast or cow milk formula feeding, substituting a special leucine-, valine-, and isoleucine-free fomula;
- To confirm the diagnosis, work with the following service(s): Utah Newborn Screening Program, (801-584-8256); See also Services below;
- For evaluation and ongoing collaborative management, consult the following service(s): Medical Genetics, (801-231-3599); See also Services below;
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 Collaboration
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
Information & Support
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
( 369 KB)
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.
ACT Sheets and Confirmatory Algorithms (ACMG)
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 (GeneReviews)
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 Acute Illness Protocol
( 33 KB)
A guideline for healthcare professionals treating the sick infant/child who has previously been diagnosed with MSUD; developed
under the direction of Dr. Harvey Levy, Senior Associate in Medicine/Genetics at Children’s Hospital Boston, and Professor
of Pediatrics at Harvard Medical School, for the New England Consortium of Metabolic Programs.
Resources for maple syrup urine disease (NLM)
Comprehensive compilation of links to information, articles, research, case studies, genetics, and more; from the National
Library of Medicine and the Genetic Alliance.
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 and Patients
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.
National Newborn Screening & Genetics Resource Center
Provides information for families and professionals about genetic screening; links to support and advocacy groups; links to
state genetic contacts; newsletters; fact sheets; data reports; publications; and more.
Patient Education
What is Maple Syrup Urine Disease (MSUD)? Genetic Science Learning Center - University of Utah
A brief educational overview of the genetics of maple syrup urine disease (MSUD) from the Genetic Science Learning Center
at the University of Utah.
Services
Newborn Screening Programs
Utah Newborn Screening Program,
more info...
44 Mario Capecchi Drive
Salt Lake City, UT 84114
Phone: 801-584-8256
Fax: 801-536-0966
http://health.utah.gov/newbornscreening
Pediatric Medical Genetics
See all Pediatric Medical Genetics services providers (3) in our database.
For other services related to this condition, browse our Services categories or search our database.
Authors
| Author: | Nicola Longo MD, PhD, 3/2007 |
| Compiled and edited by: | Alan Rope MD, 3/2007 |
| Content Last Updated: | 7/2011 |
Page Bibliography
Carleton SM, Peck DS, Grasela J, Dietiker KL, Phillips CL.
DNA carrier testing and newborn screening for maple syrup urine disease in old order mennonite communities.
Genet Test Mol Biomarkers.
2010;14(2):205-8.
PubMed abstract
Puckett RL, Lorey F, Rinaldo P, Lipson MH, Matern D, Sowa ME, Levine S, Chang R, Wang RY, Abdenur JE.
Maple syrup urine disease: further evidence that newborn screening may fail to identify variant forms.
Mol Genet Metab.
2010;100(2):136-42.
PubMed abstract
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