HLCS

The HLCS gene provides instructions for making an enzyme called holocarboxylase synthetase. This enzyme is important for the effective use of biotin, a B vitamin found in foods such as liver, egg yolks, and milk. In many of the body's tissues, holocarboxylase synthetase activates enzymes called biotin-dependent carboxylases by attaching biotin to them. These carboxylases are involved in many critical cellular functions, including the production and breakdown of proteins, fats, and carbohydrates.

Holocarboxylase synthetase may also play a role in regulating the activity of genes. In the nucleus, the enzyme likely attaches biotin molecules to histones, which are structural proteins that bind to DNA and give chromosomes their shape. Changing the shape of histones may help determine whether certain genes are turned on or off; however, it is not known how adding biotin affects gene regulation.

holocarboxylase synthetase deficiency - caused by mutations in the HLCS gene

About 30 mutations in the HLCS gene have been identified in people with holocarboxylase synthetase deficiency. Most of these mutations change a single protein building block (amino acid) in the holocarboxylase synthetase enzyme. Many of the known mutations occur in a region of the enzyme that binds to biotin. These genetic changes reduce the enzyme's ability to attach biotin to carboxylases and histones. Without biotin, carboxylases remain inactive and are unable to process proteins, fats, and carbohydrates effectively. A lack of holocarboxylase synthetase activity may also alter the regulation of certain genes that are important for normal development. Researchers believe that these defects in enzyme function underlie the breathing problems, skin rashes, and other characteristic signs and symptoms of holocarboxylase synthetase deficiency.