Summary about Disease
3-Hydroxy-3-methylglutaryl-CoA lyase (HMGCL) deficiency is a rare inherited metabolic disorder that prevents the body from properly breaking down leucine, certain fatty acids, and ketone bodies. This can lead to a buildup of toxic substances in the blood and urine, particularly during periods of fasting or illness. These toxic levels can damage the brain and other organs.
Symptoms
Symptoms can vary in severity and often appear in infancy or early childhood. Common symptoms include:
Vomiting
Lethargy
Hypotonia (floppiness)
Seizures
Metabolic acidosis
Hepatomegaly (enlarged liver)
Hypoglycemia (low blood sugar)
Unusual odor (sweaty feet-like)
Causes
HMGCL deficiency is caused by mutations in the HMGCL gene. This gene provides instructions for making the 3-hydroxy-3-methylglutaryl-CoA lyase enzyme. Mutations in this gene lead to a deficiency or absence of the enzyme, disrupting the metabolic pathway. It is inherited in an autosomal recessive pattern, meaning both parents must carry a copy of the mutated gene for a child to be affected.
Medicine Used
There is no specific cure for HMGCL deficiency. Treatment focuses on managing symptoms and preventing metabolic crises. Medications and supplements may include:
L-Carnitine: Helps remove accumulated toxic substances.
Glucose infusions: Used to treat hypoglycemia during metabolic crises.
Sodium bicarbonate or other alkalinizing agents: Used to correct metabolic acidosis.
Dietary management: A low-protein diet, especially low in leucine, and frequent feeding to avoid fasting is crucial.
Is Communicable
No, HMGCL deficiency is not communicable. It is a genetic disorder inherited from parents and cannot be spread from person to person.
Precautions
Individuals with HMGCL deficiency and their families need to take several precautions:
Strict dietary management: Adhere to the prescribed low-protein/leucine diet and frequent feeding schedule.
Avoid prolonged fasting: Ensure regular meals and snacks to prevent hypoglycemia and metabolic crises.
Prompt treatment of illness: Seek medical attention immediately for any illness, as this can trigger a metabolic crisis.
Emergency protocol: Have a written emergency protocol readily available, outlining specific actions to take during a metabolic crisis.
Monitor blood glucose and ketone levels: Regular monitoring can help detect early signs of a metabolic crisis.
How long does an outbreak last?
HMGCL deficiency isn't characterized by outbreaks in the traditional sense of infectious diseases. Instead, affected individuals experience metabolic crises when their body cannot process certain substances efficiently. The duration of a metabolic crisis can vary from a few hours to several days, depending on the severity of the trigger (e.g., infection, prolonged fasting), how quickly it is recognized, and how effectively it is treated. Early intervention is crucial to minimize the length and severity of a crisis.
How is it diagnosed?
Diagnosis typically involves:
Newborn screening: Many states screen for HMGCL deficiency as part of routine newborn screening programs using a blood sample.
Urine organic acid analysis: Elevated levels of specific organic acids in the urine, such as 3-hydroxy-3-methylglutaric acid (HMG), 3-methylglutaconic acid (MGA), and 3-hydroxyisovaleric acid, are suggestive of the disorder.
Blood acylcarnitine profile: May show elevated levels of specific acylcarnitines.
Enzyme assay: Measuring the activity of HMGCL enzyme in cultured fibroblasts or lymphocytes.
Genetic testing: Confirmation through mutation analysis of the HMGCL gene.
Timeline of Symptoms
Newborn period/Infancy: Often presents with vomiting, poor feeding, lethargy, and hypotonia shortly after birth or within the first few months of life. Hypoglycemia and metabolic acidosis may also occur early.
Childhood: Symptoms may become more apparent with increased physical activity or during periods of illness or fasting. Developmental delays or seizures may occur if the condition is not properly managed.
Adulthood: With proper management, individuals can live relatively normal lives, although they remain at risk for metabolic crises under stressful conditions.
Important Considerations
Early diagnosis and treatment are crucial to prevent severe complications and improve long-term outcomes.
Lifelong dietary management is essential.
Close monitoring by a metabolic specialist is necessary.
Genetic counseling is recommended for families with a history of HMGCL deficiency.
Education of caregivers and school personnel about the condition and emergency protocols is important.
Support groups can provide valuable resources and emotional support for affected individuals and their families.