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maple syrup urine disease type 2 - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

maple syrup urine disease type 2

MONDO:0023693

Also known as:MSUD type 2MSUD2

Overview

A maple syrup urine disease caused by mutations in DBT.

GeneticsAutosomal recessive · DBT (chr 1)

Clinical Presentation

Built from Human Phenotype Ontology (HPO) phenotype annotations and GeneReviews clinical descriptions. Features represent findings documented across known cases — not an exhaustive list of possible symptoms.

Features include always present findings: Lethargy, Severe backward arching of the body (opisthotonus), and Ketoacidosis.

Organ System	Phenotype Count	Example Features
Bones and joints	1	Severe backward arching of the body (opisthotonus)

Genetic Landscape

Assembled from HGNC gene records, ClinGen gene-disease validity evidence, and ClinVar pathogenic variant data. Validity classifications reflect the strength of published evidence linking each gene to this disease.

DBT encodes dihydrolipoamide branched chain transacylase E2 (482 aa). The branched-chain alpha-keto dehydrogenase complex catalyzes the overall conversion of alpha-keto acids to acyl-CoA and CO(2). Highest expression in Bladder (10.2 TPM) and Nerve Tibial (8.9 TPM).

Maple syrup urine disease type 2 is associated with mutations in the DBT gene on chromosome 1.

The DBT protein participates in S399C Lipo-K105-DBT, P276C Lipo-K105-DBT, and K313_Y338del Lipo-K105-DBT pathways.

DBT is classified as a druggable target (Enzyme category) with score 5.2.

Diagnosis

Drawn from GeneReviews diagnostic guidelines, newborn screening panel status (RUSP), and ClinGen gene-disease validity classifications. Reflects current clinical evidence and consensus where available.

GeneReviews

Diagnostic Criteria

Maple syrup urine disease (MSUD) is caused by decreased activity of the branched-chain alpha-ketoacid dehydrogenase complex (BCKD), the second enzymatic step in the degradative pathway of the branched-chain amino acids (BCAAs), which includes leucine, isoleucine, and valine.

Scenario 1. Abnormal newborn screening (NBS) result

NBS for MSUD is primarily based on quantification of the ratios of (leucine + isoleucine) to alanine and phenylalanine concentrations on dry blood spots.

Treatment

Compiled from FDA-approved drug records, orphan drug designations, and FDA Adverse Event Reporting System (FAERS) safety data. GeneReviews management guidance is included where available.

No approved treatments are currently available for maple syrup urine disease type 2. The disease remains an area of unmet medical need.

GeneReviews

Management Guidelines

Evaluations Following Initial Diagnosis

When maple syrup urine disease (MSUD) is suspected during the diagnostic evaluation (i.e., due to elevated concentration of leucine, isoleucine, valine, and/or alloisoleucine), metabolic treatment should be initiated immediately. Development and evaluation of treatment plans, training and education of affected individuals and their families, and avoidance of side effects of dietary treatment (i.e., malnutrition, growth failure) require a multidisciplinary approach to care with oversight and expertise from a specialized metabolic center. Consensus nutritional guidelines have been published (full text) and two peer-reviewed articles provide general guidelines about the comprehensive treatment and monitoring of MSUD: see (full text), (full text). To establish the extent of disease and needs in an individual following initial diagnosis of MSUD, the evaluations summarized (if not performed as part of the evaluation that led to diagnosis) are recommended.

Prognosis

Based on GeneReviews surveillance recommendations, HPO phenotype frequency and severity annotations, and published prevalence estimates from Orphanet and OMIM.

GeneReviews

Surveillance Guidelines

Table 10.

Recommended Surveillance for Individuals with Maple Syrup Urine Disease

Manifestation | Evaluation | Frequency/Comment

Control of amino acid other nutrient levels1

| Full amino acid profile (either from plasma or filter paper) | • For rapidly growing infants, monitoring 1x or 2x/wk

Research Landscape

Sourced from ClinicalTrials.gov and PubMed. Publication types are classified using NLM-curated article metadata; research type breakdowns reflect the nature of published work for this disease.

No clinical trials have been registered for maple syrup urine disease type 2.

14 publications have been identified in PubMed for maple syrup urine disease type 2. Research spans Case Report / Case Series (29%), Basic Science / Preclinical (21%), and Epidemiology / Natural History (21%).

Research Type	Count	% of Total
Patient case studies	4	29%

Data assembled from 6 of 12 sources · Last updated Sep 19, 2026, 2:53 PM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

OMIM

Online Mendelian Inheritance in Man

OMIM:620699

GARD

Genetic and Rare Diseases Info Center

GARD:8596

Questions for Your Care Team

→Should my partner and I meet with a genetic counselor to discuss carrier status and family planning?
→Are there specialists or centers of excellence for this condition in my area?
→Is there a patient registry I should consider joining?

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Clinical Guidance

Traditionally, the metabolic phenotype of maple syrup urine disease (MSUD) is termed classic or intermediate on the basis of residual branched-chain alpha-ketoacid dehydrogenase (BCKD) enzyme activity. Rarely, affected individuals have partial BCKD enzyme deficiency that manifests only intermittently or responds to dietary thiamine therapy . Phenotypic distinctions are not absolute: individuals with intermediate or intermittent forms of MSUD can experience severe metabolic intoxication and encephalopathy if physiologic stress is sufficient to overwhelm residual BCKD activity or this activity is reduced by transient changes in the phosphorylation state of the enzyme complex. Even in persons with relatively high baseline residual BCKD enzyme activity, episodes of metabolic intoxication can be fatal. Table 2. Clinical Phenotypes of Maple Syrup Urine Disease

Type	Age of Onset1	Clinical Features	Biochemical Signs2	% with Normal BCKD Activity3
Classic	Neonatal	Maple syrup odor of cerumen; Poor feeding; Irritability, lethargy; Opisthotonus; Focal dystonia; "Fencing," "bicycling"; Obtundation, coma; Central respiratory failure	BCAAs in plasma; plasma alloisoleucine; BCKAs in urine; Ketonuria	0%-2%
Intermediate	Variable	Maple syrup odor of cerumen; Poor growth; Poor feeding; Irritability; Developmental delays	—	—
Encephalopathy during illness	Similar to classic phenotype, though quantitatively less severe	3%-30%	—	—
Intermittent	Variable	Normal early growth development; Episodic decompensations that can be severe	Normal BCAAs when well; Similar to classic biochemical profile during illness	5%-20%
Thiamine-responsive	Variable	Similar to intermediate phenotype	Improvement of leucine tolerance biochemical profile w/thiamine therapy	2%-40% BCAAs = branched-chain amino acids; BCKAs = branched-chain alpha-ketoacids All infants with classic MSUD present during the neonatal period.

Source: GeneReviews — "Maple Syrup Urine Disease"

Kisho

maple syrup urine disease type 2

Overview

Clinical Presentation

Genetic Landscape

Diagnosis

Diagnostic Criteria

Treatment

Management Guidelines

Evaluations Following Initial Diagnosis

Prognosis

Surveillance Guidelines

Control of amino acid other nutrient levels1

Research Landscape

Medical References

External Resources

OMIM

GARD

Questions for Your Care Team

Questions for Your Care Team

Clinical Guidance

Explore clinical features

Clinical Guidance

Differential Diagnosis

Therapies Under Investigation

Clinical Trials

Delayed acquisition of developmental milestones

Recent Publications

maple syrup urine disease type 2

Overview

Clinical Presentation

Genetic Landscape

Diagnosis

Diagnostic Criteria

Treatment

Management Guidelines

Evaluations Following Initial Diagnosis

Prognosis

Surveillance Guidelines

Control of amino acid other nutrient levels1

Research Landscape

Medical References

External Resources

OMIM

GARD

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

Clinical Guidance

Explore clinical features

Clinical Guidance

Differential Diagnosis

Therapies Under Investigation

Clinical Trials

Delayed acquisition of developmental milestones

Recent Publications