Overview
3-hydroxy-3-methylglutaryl-CoA synthase deficiency, also called HMG-CoA synthase deficiency or mitochondrial HMG-CoA synthase deficiency (sometimes abbreviated as mHS deficiency), is a very rare inherited metabolic disorder. It affects the body's ability to produce ketones — a type of fuel the body normally makes from fat when food is not available, such as during fasting or illness. The gene responsible is called HMGCS2, and when it does not work properly, the liver cannot make enough ketones to keep the brain and body energized during times of low blood sugar. The condition usually first shows up in infancy or early childhood, often triggered by a period of not eating, a fever, or a stomach illness. During these episodes, a child may become very drowsy, vomit repeatedly, and have dangerously low blood sugar without the expected rise in ketones. This pattern — low blood sugar without ketones — is an important clue for doctors. With the right management, which mainly involves avoiding long periods without food and getting prompt treatment during illness, most children do well and the outlook is generally positive. There is no specific drug approved for this condition, but dietary strategies and careful monitoring can prevent serious episodes. Early diagnosis is key to preventing brain injury from repeated low blood sugar events.
Also known as:
Key symptoms:
Very low blood sugar (hypoglycemia), especially during fasting or illnessUnusual drowsiness or difficulty staying awakeRepeated vomitingEnlarged liver (hepatomegaly)Elevated liver enzymes found on blood testsAbnormally low ketone levels in the blood and urine during fastingIrritability or unusual behavior during metabolic crisesWeakness or limpness during episodesSeizures in severe casesMetabolic acidosis (too much acid in the blood) during crises
Clinical phenotype terms (3)— hover any for plain English
Autosomal recessive
Passed on when both parents carry the same gene change; often skips generations
Infantile
Begins in infancy, roughly 1 month to 2 years old
Treatments
No FDA-approved treatments are currently listed for 3-hydroxy-3-methylglutaryl-CoA synthase deficiency.
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Specialists
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Treatment Centers
8 centersBaylor College of Medicine Rare Disease Center ↗
Baylor College of Medicine
📍 Houston, TX
🏥 NORDStanford Medicine Rare Disease Center ↗
Stanford Medicine
📍 Stanford, CA
🔬 UDNNIH Clinical Center Undiagnosed Diseases Program ↗
National Institutes of Health
📍 Bethesda, MD
🔬 UDNUCLA UDN Clinical Site ↗
UCLA Health
📍 Los Angeles, CA
🔬 UDNBaylor College of Medicine UDN Clinical Site ↗
Baylor College of Medicine
📍 Houston, TX
🔬 UDNHarvard/MGH UDN Clinical Site ↗
Massachusetts General Hospital
📍 Boston, MA
🏥 NORDMayo Clinic Center for Individualized Medicine ↗
Mayo Clinic
📍 Rochester, MN
👤 Mayo Clinic Center for Individualized Medicine
🏥 NORDUCLA Rare Disease Day Program ↗
UCLA Health
📍 Los Angeles, CA
Travel Grants
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Caregiver Resources
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Mental Health Support
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Family & Caregiver Grants
Financial assistance programs specifically for caregivers of rare disease patients.
Social Security Disability
Learn how rare disease patients may qualify for SSDI/SSI benefits.
Questions for your doctor
Bring these to your next appointment
- Q1.How long can my child safely go without eating, and does this change as they get older?,What exactly should we do if my child gets sick and cannot keep food down — when do we go to the emergency room?,Should my child wear a medical alert bracelet, and what should it say?,Are there any dietary restrictions beyond avoiding long fasting periods?,Should other family members be tested for this condition?,What should I tell my child's school and their teachers about this diagnosis?,Are there any new treatments or research studies we should know about?
Common questions about 3-hydroxy-3-methylglutaryl-CoA synthase deficiency
What is 3-hydroxy-3-methylglutaryl-CoA synthase deficiency?
3-hydroxy-3-methylglutaryl-CoA synthase deficiency, also called HMG-CoA synthase deficiency or mitochondrial HMG-CoA synthase deficiency (sometimes abbreviated as mHS deficiency), is a very rare inherited metabolic disorder. It affects the body's ability to produce ketones — a type of fuel the body normally makes from fat when food is not available, such as during fasting or illness. The gene responsible is called HMGCS2, and when it does not work properly, the liver cannot make enough ketones to keep the brain and body energized during times of low blood sugar. The condition usually first sh
How is 3-hydroxy-3-methylglutaryl-CoA synthase deficiency inherited?
3-hydroxy-3-methylglutaryl-CoA synthase deficiency follows a autosomal recessive inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.
At what age does 3-hydroxy-3-methylglutaryl-CoA synthase deficiency typically begin?
Typical onset of 3-hydroxy-3-methylglutaryl-CoA synthase deficiency is infantile. Age of onset can vary across affected individuals.