Homocystinuria caused by MTHFR deficiency, or severe MTHFR deficiency, is a condition that reduces the amount of a vital enzyme called methylenetetrahydrofolate reductase (MTHFR) in the body.
This enzyme helps convert a specific amino acid called homocysteine into another amino acid called methionine. When there’s not enough MTHFR enzyme, homocysteine levels rise, leading to health issues. Symptoms of severe MTHFR deficiency can vary widely from person to person, even within the same family. Some individuals might not show any symptoms until adulthood. In infants with severe MTHFR deficiency, symptoms can include seizures, small head size, delayed development, vision problems, breathing pauses, weak muscles, and difficulty sucking. Brain scans may reveal changes over time. For those who develop symptoms later in life, the condition can lead to muscle weakness, stiffness, seizures, mental health issues, walking difficulties, and cognitive problems as they get older. Treatment involves taking specific vitamins and supplements like B6, B12, folate, and betaine to lower homocysteine levels. Seizures can be managed with medication.
This form of homocystinuria is caused by pathogenic (disease-causing) variants in the MTHFR gene and exhibits autosomal recessive inheritance. This means that both parents must be carriers to have a 25% chance to have a child with the condition. The risk of being a carrier is based on a person’s ancestry or ethnic background. For example, individuals of Sephardic Jewish descent have a 1 in 39 chance to be a carrier.
Other names for this condition are cystathionine beta synthase deficiency and homocysteinemia.
Resources:
Revised October 2023
