Dietary Supplement May Help Some with Rare Metabolic Disorder
Homocystinuria is an inherited disorder that affects the metabolism of the amino acid methionine. There is no cure for the condition, however researchers at the University of California, Berkeley are a step closer to correcting some unhealthy gene mutations with a simple dietary supplement.
Amino acids are the building blocks for protein. A number of different enzymes are needed to process these amino acids for use by the body. Those born with homocystinuria have a genetic defect which causes a deficiency of the enzyme cystathionine beta synthase (CBS) which breaks down methionine, causing a buildup in the blood. This leads to delays in growth and learning and behavior and emotional problems. Symptoms vary from person to person, but it can also affect the eyes, bones, heart and blood vessels.
Researchers have long known that just under half of those with homocystinuria will respond positively to vitamin B6 (also known as pyridoxine). The team at the Department of Molecular and Cell Biology at the California Institute of Quantitative Biosciences are closer to understanding which genetic variations will be those that are treatable with B6.
Jasper Rine PhD and colleagues “swapped” the cystathionine beta synthase gene of baker’s yeast with the gene from humans to test which variants were healthy, treatable, or untreatable with addition vitamin B6. They were able to clarify the function of 84 DNA sequence variants in this gene which will help physicians more effectively treat patients based on their particular genotypes rather than through trial and error.
Those patients who do not respond to vitamin B6 supplements need to follow a low-methionine diet which avoids cow’s milk, meat, fish, cheese, or eggs. Regular flour, dried beans, nuts, and peanut butter must also be strictly limited. In addition to dietary restrictions, patients are given a special medical formula as a substitute for milk which helps keep methionine and homocystine levels in a safe range.
Betaine may also be given in pill form. This is a vitamin-like substance found in grains and other foods which can help lower homocystine in the blood and may reduce the risk of blood clots.
Although the current study focuses on one particular metabolic disorder, the knowledge may also help learn more about other inherited disorders such as neural tube defect, cleft palate, and blindness.
J. A. Mayfield, M. W. Davies, D. Dimster-Denk, N. Pleskac, S. McCarthy, E. A. Boydston, L. Fink, X. X. Lin, A. S. Narain, M. Meighan, J. Rine. Surrogate Genetics and Metabolic Profiling for Characterization of Human Disease Alleles. Genetics, 2012; 190 (4): 1309 DOI:10.1534/genetics.111.137471