D-bifunctional Protein Deficiency - Classification

Classification

DBP deficiency can be divided into three types:

• type I, characterized by a deficiency in both the hydratase and dehydrogenase units of D-BP
• type II, in which only the hydratase unit is non-functional
• type III, with only a deficiency in the dehydrogenase unit

Type I deficient patients showed a large structural modification to the D-BP as a whole. Most of these individuals showed either a deletion or an insertion resulting in a frameshift mutation. Type II and III patients showed small scale changes in the overall structure of D-BP. Amino acid changes in the catalytic domains or those in contact with substrate or cofactors were the main cause of these variations of D-BP deficiency. Other amino acid changes were seen to alter the dimerization of the protein, leading to improper folding. Many mutations have been found in the gene coding for D-BP(HSD17B4)on the q arm two of chromosome five (5q2) in Homo sapiens, most notably individuals homozygous for a missense mutation (616S).