3-hydroxy-3-methylglutaric aciduria

General Information (adopted from Orphanet):

Synonyms, Signs: HMGCLD
HMGCL DEFICIENCY
HL DEFICIENCY
hydroxymethylglutaric aciduria
3-hydroxy-3-methylglutaryl-CoA lyase deficiency
HMG-CoA LYASE DEFICIENCY
Number of Symptoms 23
OrphanetNr: 20
OMIM Id: 246450
ICD-10: E71.1
UMLs: C1533587
MeSH:
MedDRA:
Snomed: 410059004

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal recessive
[Orphanet]
Age of onset: Neonatal
Infancy
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: Classic organic aciduria
 -Rare genetic disease
Disorder of ketone body metabolism
 -Rare genetic disease

Symptom Information: Sort by abundance 

1
 (HPO:0003535) 3-Methylglutaconic aciduria 10 / 7739
2
 (HPO:0003344) 3-Methylglutaric aciduria 6 / 7739
3
 (HPO:0003150) Glutaric aciduria 7 / 7739
4
 (HPO:0001992) Organic aciduria 28 / 7739
5
 (HPO:0001259) Coma 65 / 7739
6
 (HPO:0001262) Somnolence 20 / 7739
7
 (HPO:0002240) Hepatomegaly 467 / 7739
8
 (HPO:0001945) Fever 218 / 7739
9
 (HPO:0001943) Hypoglycemia 131 / 7739
10
 (HPO:0001942) Metabolic acidosis 81 / 7739
11
 (HPO:0001987) Hyperammonemia 50 / 7739
12
 (HPO:0003234) Decreased plasma carnitine 9 / 7739
13
 (OMIM) Sensitivity to dietary leucine 1 / 7739
14
 (OMIM) Early death 13 / 7739
15
 (OMIM) 3-hydroxyisovaleric aciduria 1 / 7739
16
 (OMIM) 3-methylglutarylcarnitinuria 1 / 7739
17
 (OMIM) No ketonuria 2 / 7739
18
 (OMIM) 3-Hydroxy-3-Methylglutaryl CoA lyase deficiency 1 / 7739
19
 (OMIM) 3-hydroxy-3-methylglutaric aciduria 1 / 7739
20
 (HPO:0003819) Death in childhood 42 / 7739
21
 (OMIM) High SGOT 1 / 7739
22
 (HPO:0000007) Autosomal recessive inheritance 2538 / 7739
23
 (MedDRA:10025482) Malaise 4 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) 3-Hydroxy-3-methylglutaryl-CoA lyase deficiency is a rare autosomal recessive disorder with the cardinal manifestations of metabolic acidosis without ketonuria, hypoglycemia, and a characteristic pattern of elevated urinary organic acid metabolites, which include 3-hydroxy-3-methylglutaric, 3-methylglutaric, and 3-hydroxyisovaleric acids. Urinary levels ...
Clinical Description OMIM Faull et al. (1976) reported a 7-month-old male infant from Australia with metabolic acidosis and hypoglycemia, who excreted organic acids suggestive of a defect in 3-hydroxy-3-methylglutaryl CoA lyase, the enzyme that catalyzes the final step of leucine degradation ...
Molecular genetics OMIM Mitchell et al. (1993) characterized mutation in the HMGCL gene causing human HL deficiency; see 613898.0001-613898.0002.

By genomic Southern blot analysis and exonic PCR, Wang et al. (1996) found that 2 of 33 HMGCL-deficient patient probands ...
Population genetics OMIM Muroi et al. (2000) stated that the incidence of HMG-CoA lyase deficiency is low, except in Saudi Arabia where the deficiency comprises 16% of all organic acidemia (Ozand et al., 1992). Otherwise, only 41 cases had been reported ...