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Deficiency of hydroxymethylglutaryl-CoA lyase(HMGCLD)

MedGen UID:
78692
Concept ID:
C0268601
Disease or Syndrome
Synonyms: 3-hydroxy-3-methylglutaric aciduria; 3-hydroxy-3-methylglutaryl-CoA lyase deficiency; 3-Hydroxy-3-Methylglutaryl-Coenzyme A Lyase Deficiency; Defect in leucine metabolism; HL deficiency; HMG CoA lyase deficiency; HMGCL DEFICIENCY; HMGCLD; Hydroxymethylglutaric aciduria
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in homozygotes. In the context of medical genetics, autosomal recessive disorders manifest in homozygotes (with two copies of the mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (HPO, OMIM, Orphanet)
SNOMED CT: Deficiency of hydroxymethylglutaryl-CoA lyase (124611007); 3-Hydroxy-3-methylglutaryl-CoA lyase deficiency (124611007); HMG-CoA lyase deficiency (124611007)
 
Gene (location): HMGCL (1p36.11)
OMIM®: 246450

Definition

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, including 3-hydroxy-3-methylglutaric, 3-methylglutaric, and 3-hydroxyisovaleric acids. Urinary levels of 3-methylcrotonylglycine may be increased. Dicarboxylic aciduria, hepatomegaly, and hyperammonemia may also be observed. Presenting clinical signs include irritability, lethargy, coma, and vomiting (summary by Gibson et al., 1988). [from OMIM]

Additional description

From GHR
3-hydroxy-3-methylglutaryl-CoA lyase deficiency (also known as HMG-CoA lyase deficiency) is an uncommon inherited disorder in which the body cannot process a particular protein building block (amino acid) called leucine. Additionally, the disorder prevents the body from making ketones, which are compounds that are used for energy during periods without food (fasting).The signs and symptoms of HMG-CoA lyase deficiency usually appear within the first year of life. The condition causes episodes of vomiting, diarrhea, dehydration, extreme tiredness (lethargy), and weak muscle tone (hypotonia). During an episode, blood sugar levels can become dangerously low (hypoglycemia), and a buildup of harmful compounds can cause the blood to become too acidic (metabolic acidosis). If untreated, the disorder can lead to breathing problems, convulsions, coma, and death. Episodes are often triggered by an infection, fasting, strenuous exercise, or other types of stress.HMG-CoA lyase deficiency is sometimes mistaken for Reye syndrome, a severe disorder that develops in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections.  https://ghr.nlm.nih.gov/condition/3-hydroxy-3-methylglutaryl-coa-lyase-deficiency

Clinical features

Coma
MedGen UID:
1054
Concept ID:
C0009421
Disease or Syndrome
A profound state of unconsciousness associated with depressed cerebral activity from which the individual cannot be aroused. Coma generally occurs when there is dysfunction or injury involving both cerebral hemispheres or the brain stem RETICULAR FORMATION.
Fever
MedGen UID:
5169
Concept ID:
C0015967
Sign or Symptom
A condition characterized by an abnormally high body temperature. In a hyperthermic state, the hypothalamic set-point is normal but body temperature increases and overrides the ability to lose heat, resulting from exogenous heat exposure or endogenous heat production.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormal enlargement of the liver.
Hypoglycemia
MedGen UID:
6979
Concept ID:
C0020615
Disease or Syndrome
A decreased concentration of glucose in the blood.
Metabolic acidosis
MedGen UID:
65117
Concept ID:
C0220981
Pathologic Function
Acid accumulation or depletion of base in the body due to buildup of metabolic acids.
Hyperammonemia
MedGen UID:
113136
Concept ID:
C0220994
Disease or Syndrome
A laboratory test result demonstrating an increased concentration of ammonia in the blood.
Glutaric aciduria
MedGen UID:
75695
Concept ID:
C0268594
Disease or Syndrome
An increased concentration of glutaric acid in the urine.
Decreased plasma carnitine
MedGen UID:
222973
Concept ID:
C1142132
Finding
A decreased concentration of carnitine in the blood.
Excessive daytime somnolence
MedGen UID:
417941
Concept ID:
C2830004
Mental or Behavioral Dysfunction
A sleep disorder characterized by excessive sleepiness and drowsiness.
3-Methylglutaric aciduria
MedGen UID:
463302
Concept ID:
C3151952
Finding
Ketonuria
MedGen UID:
56402
Concept ID:
C0162275
Finding
High levels of ketone bodies in the urine.
The following clinical feature is unrelated to Deficiency of hydroxymethylglutaryl-CoA lyase

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