Maternal hyperhomocysteinemia: a risk factor for neural-tube defects?

Area of Science:

• Biochemistry
• Nutritional Science
• Developmental Biology

Background:

• Maternal vitamin status, particularly folate, plays a role in neural-tube defect (NTD) pathogenesis.
• Maternal folate supplementation is known to prevent NTDs, but the exact metabolic mechanism remains unclear.
• Homocysteine accumulation, potentially due to folate, vitamin B12, or vitamin B6 metabolism abnormalities, is a suspected factor.

Purpose of the Study:

• To investigate the role of homocysteine accumulation in women with a history of NTD-affected offspring.
• To examine the relationship between plasma homocysteine levels, vitamin status, and methionine metabolism in nonpregnant women.
• To explore the potential metabolic derangements underlying NTD pathogenesis.

Main Methods:

• Studied 41 nonpregnant women with a history of NTDs and 50 controls with normal offspring.
• Measured fasting plasma total homocysteine and homocysteine levels 6 hours after a methionine load.
• Assessed fasting blood levels of folate, vitamin B12, and vitamin B6.

Main Results:

• Women with a history of NTDs exhibited significantly higher basal and post-methionine load homocysteine levels compared to controls.
• Nine women with NTD history and two controls showed post-methionine homocysteine levels exceeding the control mean by over 2 standard deviations.
• Skin fibroblast cystathionine synthase levels were normal in methionine-intolerant women, suggesting a remethylation disorder.

Conclusions:

• Findings suggest a disorder in homocysteine remethylation to methionine, possibly due to acquired or inherited folate or vitamin B12 metabolism issues.
• Elevated homocysteine levels can be corrected with vitamin B6 or folate administration.
• Periconceptional folate administration may prevent NTDs by addressing mild to moderate hyperhomocysteinemia.