Rare Endocrinology News

Disease Profile

3-alpha hydroxyacyl-CoA dehydrogenase deficiency

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

#N/A

ICD-10

#N/A

Inheritance

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

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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

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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.

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

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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.

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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.

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Not applicable

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Other names (AKA)

3-hydroxylacyl-CoA dehydrogenase deficiency; Medium and short chain 3-hydroxyacyl-CoA dehydrogenase deficiency; M/SCHAD;

Categories

Congenital and Genetic Diseases; Endocrine Diseases; Metabolic disorders;

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 71212

Definition
Hyperinsulinism due to short chain 3 hydroxylacyl-CoA dehydrogenase (SCHAD) deficiency is a recently described mitochondrial fatty acid oxidation disorder characterized by hyperinsulinemic hypoglycemia with seizures, and in one case fulminant hepatic failure.

Epidemiology
Less than 10 cases have been reported to date.

Clinical description
The disease can present in infancy or early childhood. It presents with the manifestations of hyperinsulinemic hypoglycemia with vomiting, lethargy and seizures. Complications include coma and sudden death. It has responded well to diazoxide.

Etiology
It is caused by a mutation in the HADH gene (4q22-q26) encoding the SCHAD protein that has a dual function both as an enzyme and an inhibitor of glutamate dehydrogenase.

Genetic counseling
The mode of inheritance is autosomal recessive and genetic counseling is possible.

Visit the Orphanet disease page for more resources.

Symptoms

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.

Medical Terms Other Names
Learn More:
HPO ID
100% of people have these symptoms
Decreased 3-hydroxyacyl-CoA dehydrogenase level
0100950
80%-99% of people have these symptoms
Abnormal circulating acetylcarnitine concentration
0012071
Confusion
Disorientation
Easily confused
Mental disorientation

[ more ]

0001289
Diarrhea
Watery stool
0002014
Dicarboxylic aciduria
0003215
Elevated hepatic transaminase
High liver enzymes
0002910
Fasting hyperinsulinemia
High blood insulin levels while fasting
0008283
Hepatic steatosis
Fatty infiltration of liver
Fatty liver

[ more ]

0001397
Hyperinsulinemic hypoglycemia
0000825
Hypoglycemic encephalopathy
0006929
Hypoglycemic seizures
0002173
Hypoketotic hypoglycemia
0001985
Increased circulating free fatty acid level
0030781
Increased Cpeptide level
0030796
Intrauterine growth retardation
Prenatal growth deficiency
Prenatal growth retardation

[ more ]

0001511
Lethargy
0001254
Neonatal hypoglycemia
Low blood sugar in newborn
0001998
Neonatal hypotonia
Low muscle tone, in neonatal onset
0001319
Proportionate short stature
0003508
Vomiting
Throwing up
0002013
5%-29% of people have these symptoms
Decreased plasma carnitine
0003234
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Feeding difficulties in infancy
0008872
Hyperammonemia
High blood ammonia levels
0001987
Lactic acidosis
Increased lactate in body
0003128
Mildly elevated creatine kinase
0008180
Motor delay
0001270
Peripheral neuropathy
0009830
Pigmentary retinopathy
0000580
Prolonged prothrombin time
0008151
1%-4% of people have these symptoms
Acute hepatic failure
Acute liver failure
0006554
Dilated cardiomyopathy
Stretched and thinned heart muscle
0001644
Hepatic necrosis
0002605
Hypertrophic cardiomyopathy
Enlarged and thickened heart muscle
0001639
Myoglobinuria
0002913
Prolonged QT interval
0001657
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance
0000007
Fulminant hepatic failure
0004448
Generalized hypotonia
Decreased muscle tone
Low muscle tone

[ more ]

0001290
Growth delay
Delayed growth
Growth deficiency
Growth failure
Growth retardation
Poor growth
Retarded growth

[ more ]

0001510

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.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Newborn Screening

    • 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.

      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 Providing General Support

        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 3-alpha hydroxyacyl-CoA dehydrogenase 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.
          • 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 3-alpha hydroxyacyl-CoA dehydrogenase deficiency. Click on the link to view a sample search on this topic.