3-hydroxy-3-methylglutaric aciduria
Findings
No curated finding names 3-hydroxy-3-methylglutaric aciduria yet. Everything below is reference data from Mondo, HPO and GenCC, not evidence about what affects it.
Definition
3-hydroxy-3-methylglutaric aciduria (3HMG) is an organic aciduria, due to deficiency of 3-hydroxy-3-methylglutaryl-CoA-lyase (a key enzyme in ketogenesis and leucine metabolism) usually presenting in infancy with episodes of metabolic decompensation triggered by periods of fasting or infections, which when left untreated are life-threatening and may lead to neurological sequelae.
Definition from the Mondo Disease Ontology (MONDO:0009520), read 2026-09-29. CC BY 4.0.
- Inheritance
- Autosomal recessive inheritance
HPO, annotations 2026-09-02
Features
65 features
What the disease is reported to present with, and how often among people who have it — never how often a feature means the disease. HPO, annotations 2026-09-02.
- Metabolic acidosisHPOHP:0001942
- 20 of 20 reported patients
- Very frequent (80% to 99% of cases)
- Reduced HMG-CoA lyase activity in cultured fibroblastsHPOHP:6000216
- 13 of 13 reported patients
- HyperammonemiaHPOHP:0001987
- 19 of 20 reported patients
- Very frequent (80% to 99% of cases)
- Elevated serum anion gapHPOHP:0031962
- 9 of 10 reported patients
- HypoglycemiaHPOHP:0001943
- 25 of 28 reported patients
- 3-Methylglutaric aciduriaHPOHP:0003344
- Very frequent (80% to 99% of cases)
Show the remaining 53
- EEG abnormalityHPOHP:0002353
- Frequent (30% to 79% of cases)
- Elevated circulating hepatic transaminase concentrationHPOHP:0002910
- Frequent (30% to 79% of cases)
- Episodic vomitingHPOHP:0002572
- 17 of 34 reported patients
- Frequent (30% to 79% of cases)
- HepatomegalyHPOHP:0002240
- 13 of 34 reported patients
- Frequent (30% to 79% of cases)
- HyperuricemiaHPOHP:0002149
- Frequent (30% to 79% of cases)
- HypotoniaHPOHP:0001252
Genes
1 gene
Germline variants in the gene encoding each protein, as classified by GenCC submitters, each in their own words. Limited, disputed and refuted submissions are listed too.
- HMGCLHGNC:5005
- Definitive · ClinGen · Autosomal recessive · 2018
- Definitive · Myriad Women's Health · Autosomal recessive · 2018
- Definitive · G2P · Autosomal recessive · 2015
- Definitive · Natera · Autosomal recessive · 2023
- Strong · Labcorp Genetics (formerly Invitae) · Autosomal recessive · 2020
- Strong · PanelApp Australia · Autosomal recessive · 2025
- Supportive · Orphanet · Autosomal recessive · 2021
Where it sits
Other names
6 names
Resolves to: 3-hydroxy-3-methylglutaric aciduria
- Also called
- 3-hydroxy-3-methylglutaryl-CoA lyase deficiency3-OH 3-Methyl glutaric aciduriadeficiency of hydroxymethylglutaryl-CoA lyaseHMG-CoA lyase deficiencyHydroxymethylglutaric aciduriahydroxymethylglutaryl-CoA lyase deficiency