Ethylmalonic encephalopathy
Ethylmalonic encephalopathy is a rare, inherited metabolic disorder that primarily damages the nervous and vascular systems, often leading to severe developmental delays and life-threatening complications in early childhood.
Overview
Ethylmalonic encephalopathy is an inherited disorder that affects several body systems, particularly the nervous system. The signs and symptoms of this condition are typically apparent at birth or begin within the first few months of life. Problems affecting the nervous system generally worsen over time, and most affected individuals survive only into early childhood.
Symptoms and Clinical Features
The disorder is characterized by a range of neurological, vascular, and gastrointestinal symptoms, including:
- Delayed development and the loss of previously acquired skills (developmental regression)
- Weak muscle tone (hypotonia)
- Seizures and abnormal movements
- Rashes of tiny red spots (petechiae) caused by bleeding under the skin
- Blue discoloration in the hands and feet due to reduced oxygen in the blood (acrocyanosis)
- Chronic diarrhea
Frequency
About 70 individuals with ethylmalonic encephalopathy have been identified worldwide, primarily in Mediterranean and Arab populations. Although the condition appears to be very rare, researchers suggest that some cases may have been misdiagnosed as other neurological disorders.
Causes & Genetic Factors
This condition results from mutations in the ETHE1 gene. This gene provides instructions for producing an enzyme active in the mitochondria, which serve as the energy-producing centers of cells. The ETHE1 enzyme is part of a metabolic pathway that breaks down sulfide (H2S)—a molecule that is critical for normal cell function at very low levels but is highly toxic at elevated levels.
Mutations in the ETHE1 gene lead to a nonfunctional version of the enzyme or prevent the enzyme from being made at all. This shortage of functional enzyme prevents sulfide from being broken down, allowing it to accumulate in cells. The buildup of sulfide interferes with mitochondrial energy production and damages tissues and organs throughout the body. Researchers believe that the toxic effects of excess sulfide in the brain, muscles, blood vessels, and intestinal lining underlie the major features of the disorder.
Inheritance
This condition is inherited in an autosomal recessive pattern. This means both copies of the gene in each cell must have mutations for the individual to be affected. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
Other Names for This Condition
- Encephalopathy, petechiae, and ethylmalonic aciduria
- EPEMA syndrome