SPTLC1

The SPTLC1 gene provides instructions for making one part (subunit) of an enzyme called serine palmitoyltransferase (SPT). The SPT enzyme is involved in making certain fats called sphingolipids. Sphingolipids are important components of cell membranes and play a role in many cell functions. The SPT enzyme, which is made up of three subunits, initiates the first step of sphingolipid production. Specifically, the enzyme combines the molecules serine and palmitoyl CoA to form a molecule called ketodihydrosphingosine. A series of additional chemical reactions produce sphingolipids. Within the cell, the SPT enzyme is mainly found on the endoplasmic reticulum, which is a structure involved in protein processing and transport.

hereditary sensory neuropathy type 1 - caused by mutations in the SPTLC1 gene

At least three mutations in the SPTLC1 gene have been found to cause hereditary sensory neuropathy type 1. These mutations change single protein building blocks (amino acids) in the SPTLC1 subunit. One mutation that has been seen in multiple affected families replaces the amino acid cysteine with the amino acid tryptophan at position 133 in the SPTLC1 subunit (written as Cys133Trp or C133W).

Altered SPTLC1 subunits can still be used to build SPT, but the resulting enzyme is nonfunctional. A lack of functional SPT enzyme leads to a decrease in sphingolipid production and a harmful buildup of certain byproducts. Sphingolipids are found in myelin, which is the covering that protects nerves and promotes the efficient transmission of nerve impulses. A decrease in sphingolipids disrupts the formation of myelin, causing nerve cells to become less efficient and eventually die. When sphingolipids are not made, an accumulation of toxic byproducts can also lead to nerve cell death. This gradual destruction of nerve cells results in loss of sensation and muscle weakness in people with hereditary sensory neuropathy type 1.