The Technion researchers discovered and characterized a genetic defect in a baby suffering from the fatal disease HFM

The baby was admitted to the "Schneider" hospital after suffering from a lack of absorption of the vitamin folic acid, which is essential for development; The discovery of the genetic defect by Technion researchers paves the way for early detection of the disease as well as genetic counseling for families in order to bring healthy offspring into the world

Researchers led by Professor Yehuda Asraf, head of the Fred Vishkovski Cancer Research Laboratory from the Faculty of Biology at the Technion, discovered and characterized a congenital genetic defect in a baby suffering from the fatal disease Hereditary Folate Malabsorption (HFM). This inherited defect results in damage to the PCFT protein responsible for the absorption of folic acid from the small intestine. Folic acid is an essential vitamin for the proper development of central body systems, including the blood system, which includes the red blood cells that are important for transporting oxygen to the tissues; The white blood cells are essential for the functioning of the immune system as well as the central nervous system.

Prof. Yaakov Amir and his staff in the Children's Department C of the "Schneider" hospital diagnosed the disease in the baby and saved his life; Prof. Rachel Strausberg and Dr. Yael Sofer also from "Schneider" Hospital continued the treatment of the baby and contacted Prof. Yehuda Asraf from the Technion. Doctoral student Inbal Lesri and microbiologist Bluma Berman, led by Professor Yehuda Asraf of the Technion, discovered and characterized the congenital genetic defect as well as the cause of the acute deterioration in the baby's health. Following the scientific discovery achieved at the Technion and published in the leading scientific journal "BLOOD", the way was paved for the early identification of the hereditary defect as well as for the provision of genetic counseling to families with the aim of bringing healthy children into the world and even for innovative therapeutic approaches.

The sick baby arrived at the "Schneider" hospital suffering from severe anemia, convulsions and stunted development. Thorough tests revealed that he suffers from an extremely low level of folic acid in his blood and spinal fluid. Therefore, it was suspected that this is probably a congenital disease called HFM in which the sick baby suffers from a lack of absorption of folic acid from the small intestine into the blood as well as from the blood into the spinal fluid. The baby was injected intravenously with a cell-available folic acid derivative called folinic acid, and this resulted in a relative normalization of the folic acid values ​​in the blood as well as a certain normalization of the folic acid level in the spinal fluid. "Schneider" hospital doctors turned to Professor Asraf, a world-renowned expert in cancer research and folic acid metabolism, and asked him to trace the genetic defect from which the baby suffers. Indeed, Professor Asraf and his research team from the Technion discovered that the two copies of the PCFT gene (donated from the father and the mother) of the baby contain the same mutation (homozygous mutation).

It should be noted that the baby's parents are first cousins ​​who carry the mutation but do not have the disease. This fact significantly increases the likelihood of having a sick offspring who inherited the mutation from both parents. The new mutation identified by the Technion researchers was inserted into the PCFT gene from a healthy person using genetic engineering methods. The insertion of the PCFT gene from a healthy person into the cells induced a very efficient absorption of folic acid, while the cells into which the defective gene from the sick baby was inserted, were devoid of any absorption capacity of the folic acid. "These findings confirmed our hypothesis that the newly discovered mutation in the PCFT gene leads to a complete paralysis of the activity of the protein that is normally responsible for the absorption of folic acid from the small intestine into the blood, hence the severe lack of folic acid in the blood and spinal fluid of the sick baby," explains Professor Asraf.

The bioinformatic approach that included building a three-dimensional model of the defective protein that the researchers took together with Dr. Fabian Glazer from the Faculty of Biology at the Technion revealed essential sites in the PCFT protein that are important for the absorption activity of folic acid. Using innovative approaches of pharmacogenetics, this study lays the foundations for predicting the possible disruption in folic acid absorption that mutations and other changes (such as polymorphisms) will cause in healthy or diseased individuals. "This paves the way for early detection, genetic counseling as well as innovative therapeutic approaches in the HFM disease which will significantly reduce the morbidity and mortality from this disease," emphasizes Professor Asraf.

Green leaves are high in folic acid

The name of folic acid (Folic acid) is derived from the Latin name Folia meaning leaves. Indeed, green leaves are rich in this vitamin, which belongs to the B-vitamin family. Mammals, including humans, are unable to produce folic acid and must therefore absorb it from food. As mentioned, green leafy vegetables such as spinach, lettuce, broccoli as well as other foods such as liver are rich in folic acid. The recommended daily dose of folic acid that we must get is 400 micrograms. Folic acid is extremely essential for the formation of nucleotides which are the building blocks of the hereditary material, DNA. In the absence or severe lack of folic acid, not enough of these building blocks will be formed, the hereditary material will not be formed, and as a result, the bone marrow will not be able to create enough new red blood cells and white blood cells, which will end in the failure of the blood system and the transport of oxygen, as well as a failure of the immune system based on The activity of white blood cells.

Furthermore, folic acid is an essential vitamin for the development of the central nervous system of the developing fetus and child. Indeed, in recent years it has been proven beyond any doubt that women who took folic acid before pregnancy as well as during pregnancy were distinctly protected against the birth of babies suffering from birth defects of the central nervous system. These findings led to the addition of folic acid to bread and breakfast cereals. In the adult, folic acid is also essential in the prevention of diseases of coronary blood vessels as well as arteriosclerosis, since in the case of a lack of folic acid in the blood, high concentrations of homocysteine ​​are formed, which is known as a substance that is harmful to the endothelial cells that make up blood vessels.