HMG-CoA Lyase Deficiency
Other Names
3-hydroxy-3-methylglutaryl-CoA lyase deficiency
HMG lyase deficiency
Hydroxymethylglutaric aciduria
HL deficiency
Overview
The lack of the enzyme 3-hydroxy-3-methylglutaryl-CoA lyase (usually expressed at high levels in the liver) impairs the formation of ketone bodies from fat and the break down of leucine [Puisac: 2010]. This results in increased utilization of glucose with hypoglycemia and accumulation of toxic metabolites. The lack of energy causes seizures and lethargy, accompanied by metabolic acidosis and hypoketotic hypoglycemia. Mutations in the HMGCL gene cause HMG-CoA lyase deficiency.Incidence
Rare [HMG-CoA Lyase Deficiency - Information for Professionals (STAR-G)]Prenatal Testing
DNA testing by amniocentesis or chorionic villus sampling (CVS) if both disease causing mutations of an affected family member have been identified; enzyme testing by maternal urine analysis possible at >23 weeks gestational age.Clinical Characteristics
With treatment, normal development and IQ are possible. However, severe episodes of hypoglycemia may still result in seizures and/or mental retardation. Without treatment, recurring metabolic crises, associated with illness or fasting, will likely result in developmental delay/mental retardation or death. Symptoms generally begin from infancy up to 3 years of age. Affected children may be healthy between metabolic crises.Initial signs/symptoms may include:
- Poor feeding
- Vomiting
- Irritability
- Lethargy
- Lab findings:
- Metabolic acidosis
- Non-ketotic hypoglycemia
- Failure to thrive
- Hepatomegaly
- Seizures
- Apnea
- Developmental delay/mental retardation
- Death
Follow-up Testing after Positive Screen
Quantitative plasma acylcarnitine profile and urine organic acids.Primary Care Management
Upon Notification of the + Screen
- Contact the family and evaluate the infant for poor feeding, vomiting, or lethargy.
- Provide emergency treatment/referral for symptoms hypoglycemia, metabolic acidosis, or seizures.
- To confirm the diagnosis, work with the following service(s): see all Newborn Screening Programs services providers (1) in our database.
- For evaluation and ongoing collaborative management, consult the following service(s): we currently have no Pediatric Genetics service providers listed, please search our Services database for related services.
If the Diagnosis is Confirmed
- Education for the family regarding signs, symptoms, and the need for urgent care when the infant becomes ill (see HMG-CoA Lyase Deficiency - Information for Parents (STAR-G) for additional information)
- Frequent, low protein, low fat, and high carbohydrate meals - avoidance of fasting
- Oral L-carnitine and cornstarch supplementation
- Bicarbonate and glucose during metabolic crisis episodes
- For those identified after irreversible consequences, assist in management, particularly with developmental and educational interventions.
Specialty Care Collaboration
Initial consultation with the following service(s):we currently have no Pediatric Genetics service providers listed, please search our Services database for related services; and ongoing collaboration if the child is affected. A dietician may work with the family to devise an optimal approach to dietary management. Genetic counseling for the family.Resources
Information & Support
For Professionals
Resources for HMG-CoA Lyase Deficiency (Disease InfoSearch)
Compilation of information, articles, research, case studies, and genetics links; from Genetic Alliance.
HMG-CoA Lyase Deficiency (OMIM)
Extensive review of literature that provides technical information on genetic disorders; Online Mendelian Inheritance in Man
site, hosted by Johns Hopkins University.
Genetics in Primary Care Institute (AAP)
The goal of this site is to increase collaboration in the care of children with known or suspected genetic disorders. It includes
health supervision guidelines and other useful resources; represents a collaboration among the Health Resources & Services
Administration, the Maternal and Child Health Bureau, and the American Academy of Pediatrics.
For Parents and Patients
HMG-CoA Lyase Deficiency - Information for Parents (STAR-G)
A fact sheet, written by a genetic counselor and reviewed by metabolic and genetic specialists, for families who have received
an initial diagnosis of this newborn disorder; Screening, Technology and Research in Genetics.
Organic Acidemia Association (OAA)
A nonprofit organization that provides information, support, events, connections with other parents, a discussion board,
and nutrition and recipe ideas.
HMG-CoA Lyase Deficiency (Genetics Home Reference)
Excellent, detailed review of condition for patients and families; sponsored by the U.S. National Library of Medicine.
Tools
ACT Sheet for Elevated C5-OH Acylcarnitine (ACMG) (
400 KB)
Contains short-term recommendations for clinical follow-up of the newborn who has screened positive; American College of Medical
Genetics.
HMG-CoA Lyase Deficiency Acute Illness Protocol (NECMP)
A guideline for health care professionals treating the sick infant/child who has previously been diagnosed with HMG-CoA lyase
deficiency; 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.
Services
Newborn Screening Programs
See all Newborn Screening Programs services providers (1) in our database.
Pediatric Genetics
We currently have no Pediatric Genetics service providers listed; search our Services database for related services.
For other services related to this condition, browse our Services categories or search our database.
Page Bibliography
Puisac B, Arnedo M, Casale CH, Ribate MP, Castiella T, Ramos FJ, Ribes A, Pérez-Cerdá C, Casals N, Hegardt FG, Pié J.
Differential HMG-CoA lyase expression in human tissues provides clues about 3-hydroxy-3-methylglutaric aciduria.
J Inherit Metab Dis.
2010;33(4):405-10.
PubMed abstract / Full Text
The pathophysiology of 3-Hydroxy-3-methylglutaric aciduria, caused by HMG-CoA lyase deficiency, is only partially understood.
Findings from this study help the understanding of the enzyme function and consequences of its deficiency and suggest the
need for pancreatic damage assessment.