Spastic Paraplegia Type 5A

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Spastic paraplegia type 5A belongs to a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by muscle stiffness (spasticity) and severe weakness in the lower limbs (paraplegia). Hereditary spastic paraplegias are often divided into two types: pure and complex. The pure types involve spasticity and weakness only in the lower limbs, while the complex types involve additional problems with other areas of the body. Additional features can include changes in vision, changes in intellectual functioning, brain abnormalities, and disturbances in nerve function (neuropathy). Spastic paraplegia type 5A is usually classified as a pure hereditary spastic paraplegia, although complex-type features have been reported in some individuals.

Genetic changes that cause disease are called pathogenic variants. Spastic paraplegia type 5A is caused pathogenic variants in the CYP7B1 gene. This gene provides instructions for making an enzyme called oxysterol 7-alpha-hydroxylase. In the brain, oxysterol 7-alpha-hydroxylase is involved in a pathway that converts certain forms of cholesterol into hormones called neurosteroids. Neurosteroids increase the ability of nerve cells (neurons) to send signals (excitability). Oxysterol 7-alpha-hydroxylase helps maintain normal cholesterol levels and regulates the effects of neurosteroids.

There are more than 80 different types of hereditary spastic paraplegia, and the combined prevalence of all these types is estimated to be 1 to 18 in 100,000 people worldwide. Spastic paraplegia type 5A likely accounts for only a small percentage of all hereditary spastic paraplegia cases. More than 50 cases of spastic paraplegia type 5A have been described in the scientific literature.

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell must have a variant to cause the disorder. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition.

Published Date: March 19, 2026
Published By: National Institutes of Health