Spinal muscular atrophy with progressive myoclonus epilepsy (Spinal muscular atrophy progressive myoclonic epilepsy With) - Gen ASAH1.

Spinal muscular atrophy progressive myoclonic epilepsy (SMA-PME) is a neurological disorder characterized by atrophy and myoclonic epilepsy. In individuals with SMA-PME, muscle atrophy of the spine it causes loss of motor neurons in the spinal cord and brainstem. After years of normal development, affected children begin to show muscle weakness and atrophy in the lower extremities, causing difficulty walking and frequent falls. Soon, muscle weakness and atrophy begin to spread throughout the body. Once the weakness reaches the muscles used in breathing and swallowing, leading to potentially fatal respiratory problems and increased susceptibility to pneumonia. A few years after muscle weakness begins, affected individuals begin to have recurrent seizures.

Most people with SMA-PME have different types of crisis. Besides myoclonic epilepsy, affected individuals may also have absence seizures, which causes loss of consciousness for a short period may, or may not be accompanied by muscle spasms. Often seizures in individuals affected by the disease increase in frequency over time and generally are not fully controlled with medication. In addition, these individuals may have tremors that usually affect hands. Some people with SMA-PME develop sensorineural hearing loss. Individuals with SMA-PME have a lower life expectancy and live, usually until late childhood or early adulthood. Often the cause of death in these individuals is respiratory failure or pneumonia.

Spinal muscular atrophy progressive myoclonic epilepsy is due to mutations in the gene ASAH1, located on the short arm of chromosome 8 (8p22). This gene encodes an enzyme called acid ceramidase found in lysosomes. Within the lysosomes, the enzyme decomposes ceramides. In general, ceramides are inside the membranes surrounding the cells and play a role in differentiation, proliferation and apoptosis. Moreover, ceramides are a component of myelin that insulates and protects nerve cells. When ceramides need replacement, traveling to lysosomes where acid ceramidase enzyme decomposes in a fat called sphingosine and a fatty acid. These two degradation products are recycled to create new ceramides for use by the body.

They have identified at least four mutations in the gene ASAH1 leading to spinal muscular atrophy progressive myoclonic epilepsy (SMA-PME). These mutations cause a reduction of the activity of acid ceramidase at a lower level than a third of normal. The decreased activity this enzyme leads to inefficient breakdown of ceramides and altered production of degradation products of fatty acids and sphingosine. Although the exact mechanism is unknown, the increase in ceramide and reduced fatty acids sphingosine probably play a role in the development of disease characteristics.

This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated with spinal muscular atrophy progressive myoclonic epilepsy (SMA-PME) by PCR amplification of complete exons ASAH1 gene, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).