What are the genetic changes related to congenital neuronal ceroid lipofuscinosis ?
Mutations in the CTSD gene cause congenital NCL. The CTSD gene provides instructions for making an enzyme called cathepsin D. Cathepsin D is one of a family of cathepsin proteins that act as proteases, which modify proteins by cutting them apart. Cathepsin D is found in many types of cells and is active in lysosomes, which are compartments within cells that digest and recycle different types of molecules. By cutting proteins apart, cathepsin D can break proteins down, turn on (activate) proteins, and regulate self-destruction of the cell (apoptosis).  CTSD gene mutations that cause congenital NCL lead to a complete lack of cathepsin D enzyme activity. As a result, proteins and other materials are not broken down properly. In the lysosomes, these materials accumulate into fatty substances called lipopigments. These accumulations occur in cells throughout the body, but neurons are likely particularly vulnerable to damage caused by the abnormal cell materials and the loss of cathepsin D function. Early and widespread cell death in congenital NCL leads to severe signs and symptoms and death in infancy.