Homocystinuria due to defect in methylation- MTHFR deficiency
Overview
A inborn error of metabolism where an inherited deficiency of methylene tetrahydrofolate reductase causes symptoms of ranging severity - from asymptomatic to severe neurological degeneration and premature death.
Symptoms
* Developmental delay * Motor abnormality * Gait abnormality * Mental retardation * Seizures * Psychiatric manifestations * Moderate homocystinuria * Homocystinemia * Premature death * Asymptomatic * Developmental delay * Motor abnormality * Gait abnormality * Mental retardation * Seizures * Psychiatric manifestations * Moderate homocystinuria * Homocystinemia * Premature death * Asymptomatic
Diagnosis
Diagnosis may be suspected after analysis of amino acids by chromatography and measurements of total plasma homocysteine levels revealing highly elevated values of >100 micromol/L. Other biological findings include low levels of methyltetrahydrofolate in both the plasma and cerebrospinal fluid. Diagnosis is confirmed by measuring enzyme activity in lymphocytes or fibroblasts. The differential diagnosis should include other homocysteine remethylation disorders. Prenatal diagnosis is feasible through molecular or enzymatic analysis.
Prognosis
The prognosis is variable.
Treatment
Treatment of severe deficiency revolves around the administration of high-dose betaine, in combination with methionine, pyridoxine, vitamin B12 and folic or folinic acid supplements.