Spastic paraplegia type 3A

Spastic paraplegia type 3A is part of a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by progressive muscle stiffness (spasticity) and the development of paralysis of the lower limbs (paraplegia). Hereditary spastic paraplegias are divided into two types: pure and complex. The pure types involve only the lower limbs, whereas the complex types also involve the upper limbs (to a lesser degree) and the nervous system. Spastic paraplegia type 3A is a pure hereditary spastic paraplegia.

In addition to the usual muscle stiffness and weakness characteristic of the hereditary spastic paraplegias, people with spastic paraplegia type 3A can also experience progressive muscle wasting (amyotrophy) in the lower limbs, reduced bladder control, and an abnormal curvature of the spine (scoliosis). The signs and symptoms of spastic paraplegia type 3A usually appear in the first decade of life. The condition progresses very slowly, and some people may need walking support late in life.

Symptoms of spastic paraplegia type 3A commonly appear before the age of 10. The specific incidence of this disorder is unknown.

Mutations in the ATL1 gene cause spastic paraplegia type 3A. The ATL1 gene provides instructions for producing a protein called atlastin-1. Atlastin-1 is found throughout the body, particularly in the brain. In cells, this protein is found in structures known as the endoplasmic reticulum and the Golgi apparatus, which are involved in the movement of proteins and cell components within the cell.

Atlastin-1 likely plays a role in the transportation of cell components and in the formation of the endoplasmic reticulum and Golgi apparatus, each of which is involved in the growth of axons (specialized extensions of nerve cells that transmit nerve impulses). Atlastin-1 is necessary for the formation and growth of axons; however, its precise function remains unclear. Researchers suggest that mutations in atlastin-1 cause the signs and symptoms of spastic paraplegia type 3A by interfering with the protein's role in axonal growth.

Read more about the ATL1 gene.

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

In some cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.