Beta-lipoproteins are involved in the transport of fats, cholesterol and fat soluble vitamins in the bloodstream. As fats and vitamins are essential to the development of cells and tissues, beta-lipoproteins play an essential physiological role in the body. MTTP is involved in the production of beta-lipoproteins by catalyzing the transport of cholesteryl ester, phospholipid and triglyceride from phospholipid surfaces.
Mutations in the MTTP gene have been associated with abetalipoproteinemia, a rare disorder characterized by the malabsorption of fats and lipid soluble vitamins resulting in hypocholesterolemia and vitamin deficiency. Mutations can result in the absence of the MTP protein or in a short non-functional version of it.
MTTP is located on the long arm of chromosome 4. The approximately 60 kb long gene is made up of 19 exons. MTTP encodes a 97 kDa large subunit that is 894 amino acids long. This subunit forms a heterodimer along with the protein disulfide isomerase.
More than 30 mutations in the MTTP gene have been linked to abetalipoproteinemia. Of these, the c.2593G-T transversion, which results in the replacement of glycine with a stop signal (G865X). The latter has been found to be more prevalent in Ashkenazi Jewish populations.
Rafique and Zia (2011) described a 5 month old Saudi male presenting with chronic diarrhoea and failure to thrive. The child was born to healthy unrelated parents. He was severely malnourished and had steatorrhic stools, a mildly distended abdomen and brittle, sparse and hypopigmented hair. Biochemical investigations uncovered very low levels of cholesterol, triglycerides and LDL while VLDL and chylomicrons were not detected. Blood films revealed acanthocytosis and stool analysis uncovered several fat globules, occult blood traces and absence of reducing substances. Multiple fat globules were revealed in a biopsy of the jejunal mucosa. The epithelial cells were found to be deficient in MTP protein. Genetic testing detected a homozygous 481 kb contiguous deletion between markers RH 8338 and RH 59351 involving MTP and six other genes. The patient was diagnosed with abetalipoproteinemia and treated with medium chain triglycerides (MCT) formula and fat soluble vitamins at high doses.