HMG CoA lyase deficiency - Rare Infectious Disease News

Rare Infectious Disease News

8387

Rare Infectious Disease News

Disease Profile

HMG CoA lyase deficiency

Unknown

US Estimated

Europe Estimated

Age of onset

All ages

ICD-10

E71.1

Inheritance

HMG CoA lyase deficiency is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene (and are referred to as carriers), but they typically do not show signs and symptoms of the condition. When parents who are both carriers of an autosomal recessive condition have a child, there is a 1 in 4 (25%) chance for each child to have the condition, a 1 in 2 (50%) chance for each child to be a carrier like each of the parents, and a 1 in 4 (25%) chance for the child not to have the condition and not be a carrier.^[1]

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

Not applicable

Other names (AKA)

3-hydroxy-3-methylglutaryl-CoA lyase deficiency; Defect in leucine metabolism; HMG-CoA lyase deficiency;

Summary

HMG CoA lyase deficiency is an inherited disorder in which the body cannot process a protein called leucine or make ketones. Ketones are used for energy during periods of fasting. The signs and symptoms of condition usually appear within the first year of life and include 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. Mutations in the HMGCL gene cause HMG-CoA lyase deficiency, and this condition is inherited in an autosomal recessive pattern.^[1]^[2] Treatment usually involves a team of specialists including a metabolics and/or genetics specialist and a dietician and may include avoidance of fasting, a low leucine diet, and supplementation with L-carnitine.^[3]

Symptoms

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 one of these episodes, 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 (seizures), coma, and death. Episodes are often triggered by an infection, fasting (not eating enough), strenuous exercise, or other types of stress.^[1]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Newborn Screening

The Newborn Screening Coding and Terminology Guide has information on the standard codes used for newborn screening tests. Using these standards helps compare data across different laboratories. This resource was created by the National Library of Medicine.
An ACTion (ACT) sheet is available for this condition that describes the short-term actions a health professional should follow when an infant has a positive newborn screening result. ACT sheets were developed by experts in collaboration with the American College of Medical Genetics.
An Algorithm flowchart is available for this condition for determining the final diagnosis in an infant with a positive newborn screening result. Algorithms are developed by experts in collaboration with the American College of Medical Genetics.

Treatment

The resources below provide information about treatment options for this condition. If you have questions about which treatment is right for you, talk to your healthcare professional.

Management Guidelines

Orphanet Emergency Guidelines is an article which is expert-authored and peer-reviewed that is intended to guide health care professionals in emergency situations involving this condition.

Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
3-Methylglutaric aciduria		0003344
Hyperammonemia	High blood ammonia levels	0001987
Metabolic acidosis		0001942
Nonketotic hypoglycemia		0001958
30%-79% of people have these symptoms
Anemia	Low number of red blood cells or hemoglobin	0001903
Anorexia		0002039
Apathy	Lack of feeling, emotion, interest	0000741
Elevated hepatic transaminase	High liver enzymes	0002910
Episodic vomiting		0002572
Hepatomegaly	Enlarged liver	0002240
Hyperuricemia	High blood uric acid level	0002149
Increased serum lactate		0002151
Lethargy		0001254
Lipid accumulation in hepatocytes		0006561
Muscular hypotonia	Low or weak muscle tone	0001252
Prolonged prothrombin time		0008151
Recurrent hypoglycemia	Recurrent low blood sugar levels	0001988
Reye syndrome-like episodes		0006582
Seizure		0001250
Tachypnea	Increased respiratory rate or depth of breathing	0002789
5%-29% of people have these symptoms
Apnea		0002104
Dehydration		0001944
Diarrhea	Watery stool	0002014
Edema	Fluid retention Water retention [ more ]	0000969
Encephalopathy		0001298
Fatigue	Tired Tiredness [ more ]	0012378
Fever		0001945
Hyporeflexia	Decreased reflex response Decreased reflexes [ more ]	0001265
Hypotension	Low blood pressure	0002615
Hypsarrhythmia		0002521
Intellectual disability, mild	Mental retardation, borderline-mild Mild and nonprogressive mental retardation Mild mental retardation [ more ]	0001256
Intellectual disability, moderate	IQ between 34 and 49	0002342
Intellectual disability, severe	Early and severe mental retardation Mental retardation, severe Severe mental retardation [ more ]	0010864
Jaundice	Yellow skin Yellowing of the skin [ more ]	0000952
Ketonuria		0002919
Leukocytosis	Elevated white blood count High white blood count Increased blood leukocyte number [ more ]	0001974
Leukopenia	Decreased blood leukocyte number Low white blood cell count [ more ]	0001882
Myoclonus		0001336
Pallor		0000980
Thrombocytosis	Increased number of platelets in blood	0001894
Weight loss		0001824
1%-4% of people have these symptoms
Acute pancreatitis	Acute pancreatic inflammation	0001735
Ataxia		0001251
Cardiac arrest	Heart stops beating	0001695
Dilated cardiomyopathy	Stretched and thinned heart muscle	0001644
Dysarthria	Difficulty articulating speech	0001260
Global developmental delay		0001263
Hypoglycemic coma	Coma caused by low blood sugar	0001325
Hypothermia	Abnormally low body temperature	0002045
Leukoencephalopathy		0002352
Microcephaly	Abnormally small skull Decreased circumference of cranium Decreased size of skull Reduced head circumference Small head circumference [ more ]	0000252
Psychomotor retardation		0025356
Spastic hemiparesis		0011099
Percent of people who have these symptoms is not available through HPO
Abnormality of the cerebral white matter		0002500
Autosomal recessive inheritance		0000007
Coma		0001259
Death in childhood		0003819
Decreased plasma carnitine		0003234
Decreased prothrombin time		0032198
EEG abnormality		0002353
Excessive daytime somnolence	Excessive daytime sleepiness More than typical sleepiness during day [ more ]	0001262

Conditions with similar signs and symptoms from Orphanet
Differential diagnosis includes sepsis, fatty acid oxidation disorders, organic acidurias and Reye's syndrome. Visit the Orphanet disease page for more information.

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

FOD (Fatty Oxidation Disorder) Family Support Group
P.O. Box 54
Okemos, MI 48805-0054
Telephone: +1-517-381-1940 [8am 8pm EST every day]
Fax: +1-866-290-5206
E-mail: [email protected]
Website: https://fodsupport.org/
Genetic Metabolic Dietitians International
P.O. Box 1462
Hillsborough, NC 27278
E-mail: [email protected]
Website: https://www.gmdi.org/
Organic Acidemia Association
9040 Duluth Street
Golden Valley, MN 55427
Telephone: 763-559-1797
Fax: 866-539-4060
E-mail: [email protected]
Website: https://www.oaanews.org/

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

Genetics Home Reference (GHR) contains information on HMG CoA lyase deficiency. This website is maintained by the National Library of Medicine.
The Screening, Technology And Research in Genetics (STAR-G) Project has a fact sheet on this condition, which was written specifically for families that have received a diagnosis as a result of newborn screening. This fact sheet provides general information about the condition and answers questions that are of particular concern to parents.

In-Depth Information

The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
The New England Consortium of Metabolic Program has written medical guidelines called acute care protocols for HMG CoA lyase deficiency for health care professionals.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss HMG CoA lyase deficiency. Click on the link to view a sample search on this topic.

References

3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency. Genetics Home Reference. October 2008; https://ghr.nlm.nih.gov/condition/3-hydroxy-3-methylglutaryl-coa-lyase-deficiency.
Bandeira A, Vilarinho L. 3-hydroxy-3-methylglutaric aciduria. Orphanet. August 2014; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=20.
Organic Acid Oxidation Disorders: 3-hydroxy-3-methylglutaryl-CoA lyase deficiency. Screening, Technology and Research in Genetics (STAR-G). April 20, 2016; https://www.newbornscreening.info/Parents/organicaciddisorders/HMGCoA.html#4.

Rare Infectious Disease News

Rare Infectious Disease News

Rare Infectious Disease News

All ages

E71.1

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

X-linked dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

Not applicable

Other names (AKA)

Categories

Summary

Symptoms

Diagnosis

Newborn Screening

Treatment

Management Guidelines

Related diseases

Organizations

Organizations Supporting this Disease

Learn more

Where to Start

In-Depth Information

References

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.