SNP Shot: Genomic Insights

MEGDEL syndrome is a genetic condition affecting multiple systems in the body. Its name is an acronym representing key characteristics: elevated levels of 3-methylglutaconic acid in the urine (3-methylglutaconic aciduria, or MEG), deafness (D), brain disease (encephalopathy, or E), and brain abnormalities similar to those seen in Leigh syndrome (L).

A hallmark of MEGDEL syndrome is 3-methylglutaconic aciduria, indicated by unusually high amounts of 3-methylglutaconic acid in urine. This feature is used to diagnose MEGDEL syndrome as part of a broader group of metabolic disorders. Individuals with MEGDEL syndrome also exhibit elevated urine levels of 3-methylglutaric acid.

Infants with MEGDEL syndrome develop sensorineural hearing loss, resulting from changes within the inner ear. This hearing impairment progressively worsens.

Encephalopathy, or brain dysfunction, is another significant aspect of MEGDEL syndrome. In infancy, this presents as difficulties with feeding, failure to thrive (inadequate growth and weight gain), and reduced muscle tone (hypotonia). Over time, affected infants develop involuntary muscle contractions (dystonia) and muscle stiffness (spasticity), which become more pronounced. These neurological and muscular issues lead to delays in mental and motor skill development (psychomotor delay), and may result in the loss of previously acquired abilities. Those with MEGDEL syndrome have intellectual disability and are unable to develop speech.

Brain scans of individuals with MEGDEL syndrome reveal changes resembling those observed in Leigh syndrome, a related neurological disorder. These brain changes are referred to as Leigh-like disease.

Other common features of MEGDEL syndrome include low blood sugar (hypoglycemia) in newborns, liver problems (hepatopathy) during infancy that can be severe but tend to improve by early childhood, and episodes of abnormally high levels of lactic acid in the blood (lactic acidosis).

The lifespan of individuals with MEGDEL syndrome is currently unknown. Due to the serious health complications associated with the syndrome, some affected infants do not survive beyond infancy.

Inheritance:

MEGDEL syndrome follows an autosomal recessive inheritance pattern. This means that a person must inherit two mutated copies of the responsible gene, one from each parent, to develop the condition. Parents who each carry one copy of the mutated gene are typically unaffected and do not display symptoms of the syndrome.