Home > Newborn Disorders > HMG-CoA lyase deficiency

HMG-CoA lyase deficiency

Disorder Category

an organic acid disorder

Screening

Finding

elevated C5-OH (acylcarnitine)

Tested By

tandem mass spectrometry (MS/MS); sensitivity: NA; specificity: NA

Names

HMG-CoA lyase deficiency

3-hydroxy-3-methylglutaryl-CoA lyase deficiency

HMG lyase deficiency

Hydroxymethylglutaric aciduria

HL deficiency

ICD-9

270.9, Disorder of amino-acid metabolism

Overview

The lack of this enzyme (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.

Prevalence

rare [HMG-CoA lyase deficiency info for professionals (STAR-G)]

Inheritance

autosomal recessive

Prenatal Testing

DNA testing by amniocentesis or CVS; enzyme testing by urine analysis.

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 treatement, 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, and
    • non-ketotic hypoglycemia.

If not treated promptly and consistently, patients may experience:
  • failure to thrive,
  • hepatomegaly,
  • seizures,
  • apnea,
  • developmental delay/mental retardation, and
  • death.

Treatment consists in limited fasting time, prompt treatment of infections/fever/gastroenteritis, use of corn-starch, and carnitine supplementation.

Follow-up on positive screening test

Quantitative plasma acylcarnitine profile and urine organic acids.

Primary care management

Upon notification of the + screen

If the diagnosis is confirmed

  • Educate the family regarding signs, symptoms, and the need for urgent care when the infant becomes ill (see HMG-CoA lyase deficiency info 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 and ongoing collaboration, particularly for dietary management. Genetic counseling for the family.

Resources

Information & Support

For Professionals

HMG-CoA lyase deficiency info for professionals (STAR-G)
From the Screening, Technology and Research in Genetics (STAR-G) program, one of a series of Disorder Fact Sheets for Professionals; structured list of information about the condition, with links to more information.

ACT Sheet for Elevated C5-OH Acylcarnitine (ACMG) (PDF Document 400 KB)
Developed by the American College of Medical Genetics, includes recommended responses to positive newborn screening test results, diagnostic evaluation, clinical expectations, and sources of additional information.

ACT Sheets and Confirmatory Algorithms (ACMG)
The American College of Medical Genetics (ACMG) has developed ACTion (ACT) Sheets and algorithms for responding to positive newborn screening test results. This page contains a table with links to all of the ACT Sheets and related algorithms.

HMG-CoA lyase deficiency Acute Illness Protocol (NECMP)
A guideline for healthcare 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.

Resources for HMG-CoA lyase deficiency (NLM)
Comprehensive compilation of links to information, articles, research, case studies, genetics, and more; from the National Library of Medicine and the Genetic Alliance.

HMG-CoA lyase deficiency (OMIM)
Extensive review of the literature, including clinical features and genetics, from the Online Mendelian Inheritance in Man site, hosted by Johns Hopkins University, providing technical information for providers on genetic disorders, links to MEDLINE, and links to other scientific information and sites.

Organic Acidemias (GeneReviews)
Excellent and extensive review by Margretta Seashore, MD on the GeneReviews site; includes causes, evaluation strategy, genetic counseling, management, resources, and references.

For Parents and Patients

HMG-CoA lyase deficiency info for parents (STAR-G)
From the Screening, Technology and Research in Genetics (STAR-G) program, providing information for parents about HMG lyase deficiency and links to other sites including parent support groups.

Organic Acidemia Association (OAA)
A non-profit organization that provides information for parents and providers; newsletters; event information; connections with other parents; a listserv; a discussion board; information about nutrition and recipes; translation of their web pages into five other languages; hosting of the Propionic Acidemia Research Network and other research funds; and links to other sites.

HMG-CoA lyase deficiency (Genetics Home Reference)
Excellent, detailed review aimed at patients and families from the National Library of Medicine's Genetics Home Reference site.

Services

Genetics-related clinical services throughout the world can be found through Genetics Clinic Directory (GeneTests).

Newborn Screening Programs

Utah Newborn Screening Program, more info...
44 Mario Capecchi Drive
Salt Lake City, UT 84114
Phone: 801-584-8256
Fax: 801-536-0966
http://health.utah.gov/newbornscreening

Pediatric Medical Genetics

See all Pediatric Medical Genetics services providers (3) in our database.

For other services related to this condition, browse our Services categories or search our database.

Helpful Articles

PubMed search on HMG-CoA lyase deficiency and newborn infant in the last 5 years.

Authors

Reviewing Author: Nicola Longo MD, PhD, 3/2011
Compiled and edited by: Alfred Romeo RN, PhD, 3/2007
Content Last Updated: 4/2011

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.