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MEGDEL syndrome
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Condition

MEGDEL syndrome

MEGDEL syndrome is a rare, multi-system inherited disorder characterized by 3-methylglutaconic aciduria, sensorineural deafness, encephalopathy, and Leigh-like brain changes.

Overview

MEGDEL syndrome is an inherited disorder that affects multiple systems of the body. The name of the condition is an acronym derived from its primary clinical features:

  • MEG: 3-methylglutaconic aciduria
  • D: Deafness
  • E: Encephalopathy
  • L: Leigh-like disease

Due to the severity of these health problems, some affected individuals do not survive past infancy. The overall life expectancy for those with the condition is currently unknown.

Symptoms and Clinical Features

The symptoms of MEGDEL syndrome emerge early in life and progress over time:

Metabolic and Brain Features

  • 3-methylglutaconic aciduria: Abnormally high levels of 3-methylglutaconic acid in the urine. Affected individuals also show high urine levels of 3-methylglutaric acid.
  • Brain dysfunction (encephalopathy), which leads to feeding difficulties, weak muscle tone (hypotonia), and an inability to grow and gain weight at the expected rate (failure to thrive) during infancy.
  • Brain changes visible on medical imaging that resemble Leigh syndrome (referred to as Leigh-like disease).
  • Episodes of abnormally high lactic acid in the blood (lactic acidosis) and low blood glucose (hypoglycemia) in newborns.

Neurological and Sensory Progressions

  • Hearing loss caused by changes in the inner ear (sensorineural deafness) that begins in infancy and gradually worsens.
  • Involuntary muscle tensing (dystonia) and muscle stiffness (spasticity) that develop after infancy and worsen over time.
  • Delayed development of mental and movement abilities (psychomotor delay) or a loss of previously acquired skills. Affected individuals have intellectual disability and do not learn to speak.
  • Infantile liver problems (hepatopathy) that can be severe but typically improve by early childhood.

Frequency

MEGDEL syndrome is a rare disorder with an unknown prevalence. At least 40 affected individuals have been documented in the medical literature.

Causes and Risk Factors

MEGDEL syndrome is caused by mutations in the SERAC1 gene. The protein produced by this gene is believed to be involved in remodeling phospholipids, specifically a phospholipid called phosphatidylglycerol.

Phosphatidylglycerol is used to make cardiolipin, a crucial component of the membrane surrounding mitochondria (the energy-producing centers of cells). Cardiolipin is essential for these structures to function properly.

Mutations in the SERAC1 gene result in little to no functional SERAC1 protein. This impairs phosphatidylglycerol remodeling and alters the composition of cardiolipin. Researchers believe that abnormal cardiolipin compromises mitochondrial function, reducing cellular energy production. This energy deficit leads to the neurological and hearing problems characteristic of MEGDEL syndrome. The mitochondrial dysfunction is also thought to cause the abnormal release of 3-methylglutaconic acid in the urine.

Inheritance

This condition is inherited in an autosomal recessive pattern, meaning both copies of the gene in each cell have mutations. The parents of an affected child each carry one copy of the mutated gene but typically do not show signs or symptoms of the condition.

Other Names for This Condition

  • 3-methylglutaconic aciduria type IV with sensorineural deafness, encephalopathy, and Leigh-like syndrome
  • 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome
  • MEGDHEL syndrome
  • SERAC1 defect

Frequently Asked Questions

Diagnosis requires a combination of clinical assessment, metabolic testing, and genetic confirmation. Urine organic acid analysis will reveal elevated 3‑methylglutaconic acid and 3‑methylglutaric acid. Blood lactate and glucose levels are monitored for acidosis and hypoglycemia. A brain MRI typically shows Leigh‑like lesions in the basal ganglia or brainstem. Finally, a DNA test for pathogenic variants in the AGK gene confirms the diagnosis.
Newborns with MEGDEL syndrome often show poor feeding, persistent vomiting, and low muscle tone (hypotonia). They may also have episodes of low blood sugar (hypoglycemia) or high lactic acid (lactic acidosis) that can be detected in routine newborn screening or metabolic panels. Early detection of these metabolic abnormalities should prompt a specialist evaluation for MEGDEL syndrome.
While there is no cure, supportive care can improve quality of life. Early cochlear implantation or hearing aids can help with sensorineural deafness. Physical and occupational therapy can address hypotonia, spasticity, and developmental delays. Some clinicians trial high‑dose thiamine or carnitine supplementation, but evidence is limited; these should be discussed with a metabolic specialist.
Life expectancy is variable; many infants with severe metabolic crises do not survive beyond the first year, but some individuals live into adolescence or adulthood with intensive support. Long‑term care involves multidisciplinary teams: metabolic specialists, neurologists, audiologists, nutritionists, and physiotherapists. Regular monitoring of metabolic status, early intervention for feeding difficulties, and proactive management of infections are essential for maximizing function and comfort.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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