Some fats called lysophosphatidylcholines including omega-3 fatty acids that are essential for human life have been shown to be essential for proper brain growth and development for the first time. Some diseases that inhibit brain development were found to originate in a genetic defect in the protein that transports lysophosphatidylcholines from the blood to the brain. Associate Professor David Silver from Duke-NUS Graduate Medical School in Singapore and Professor Joseph Gleeson from Rockefeller University presented these discoveries in the edition of the journal Nature Genetics.
Major facilitator superfamily domain-containing protein 2 (Mfsd2a) had previously been determined to be the protein that transports lysophosphatidylcholines from the blood to the brain by the same group of researchers. The researchers found that two different defects in the Mfsd2a are responsible for the development of small brain size. The defects in the transport protein inevitably produce microcephaly. One mutation is inevitably lethal and the other is not.
The researchers examined two families that had a history of Mfsd2a mutations in Libya and in Pakistan. The family in Libya had a mutation that prevented the transport of lysophosphatidylcholines to the brain. The children in the Libyan that inherited the mutation all died by the age of six and all exhibited small brain size.
A second family in Pakistan exhibited a different mutation that reduced the ability of Mfsd2a to deliver lysophosphatidylcholines but did not eliminate the transport completely. The children from this family that inherited the mutation all developed microcephaly but did not die. The children did develop dysfunctions associated with underdeveloped brains including loss of speech, lack of control of limbs, and intellectual difficulties.
This research is the first to directly associate a transport protein mutation with a brain disease that is common in many parts of the world. The researchers suggest that there may be a possibility to reverse the mutation or the effects of the mutation. The treatment may be accomplished by a simple improvement in diet that may be complicated due to the countries and governments where the ailment is most common. The condition is rare in the United States with only 440 known cases of the disease having been reported.