|http://ghr.nlm.nih.gov/ A service of the U.S. National Library of Medicine®|
Spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) is a neurological condition that causes muscle weakness and wasting (atrophy) and a combination of seizures and uncontrollable muscle jerks (myoclonic epilepsy).
In individuals with SMA-PME, spinal muscular atrophy results from a loss of specialized nerve cells, called motor neurons, in the spinal cord and the part of the brain that is connected to the spinal cord (the brainstem). After a few years of normal development, affected children begin experiencing muscle weakness and atrophy in the lower limbs, causing difficulty walking and frequent falls. The muscles in the upper limbs are later affected, and soon the muscle weakness and atrophy spreads throughout the body. Once weakness reaches the muscles used for breathing and swallowing, it leads to life-threatening breathing problems and increased susceptibility to pneumonia.
A few years after the muscle weakness begins, affected individuals start to experience recurrent seizures (epilepsy). Most people with SMA-PME have a variety of seizure types. In addition to myoclonic epilepsy, they may have generalized tonic-clonic seizures (also known as grand mal seizures), which cause muscle rigidity, convulsions, and loss of consciousness. Affected individuals can also have absence seizures, which cause loss of consciousness for a short period that may or may not be accompanied by muscle jerks. In SMA-PME, seizures often increase in frequency over time and are usually not well-controlled with medication. Individuals with SMA-PME may also have episodes of rhythmic shaking (tremors), usually in the hands; these tremors are not thought to be related to epilepsy.
Some people with SMA-PME develop hearing loss caused by nerve damage in the inner ear (sensorineural hearing loss).
Individuals with SMA-PME have a shortened lifespan; they generally live into late childhood or early adulthood. The cause of death is often respiratory failure or pneumonia.
SMA-PME is a rare disorder; approximately a dozen affected families have been described in the scientific literature.
SMA-PME is caused by mutations in the ASAH1 gene. This gene provides instructions for making an enzyme called acid ceramidase. This enzyme is found in lysosomes, which are cell compartments that digest and recycle materials. Within lysosomes, acid ceramidase breaks down fats called ceramides into a fat called sphingosine and a fatty acid. These two breakdown products are recycled to create new ceramides for the body to use. Ceramides have several roles within cells. For example, they are a component of a fatty substance called myelin that insulates and protects nerve cells.
ASAH1 gene mutations that cause SMA-PME result in a reduction of acid ceramidase activity to a level less than one-third of normal. Inefficient breakdown of ceramides and impaired production of its breakdown products likely play a role in the nerve cell damage that leads to the features of SMA-PME, but the exact mechanism is unknown.
Changes in this gene are associated with spinal muscular atrophy with progressive myoclonic epilepsy.
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
These resources address the diagnosis or management of spinal muscular atrophy with progressive myoclonic epilepsy and may include treatment providers.
You might also find information on the diagnosis or management of spinal muscular atrophy with progressive myoclonic epilepsy in Educational resources (http://www.ghr.nlm.nih.gov/condition/spinal-muscular-atrophy-with-progressive-myoclonic-epilepsy/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/spinal-muscular-atrophy-with-progressive-myoclonic-epilepsy/show/Patient+support).
General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).
To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.
You may find the following resources about spinal muscular atrophy with progressive myoclonic epilepsy helpful. These materials are written for the general public.
You may also be interested in these resources, which are designed for healthcare professionals and researchers.
For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).
atrophy ; autosomal ; autosomal recessive ; brainstem ; breakdown ; cell ; ceramides ; distal ; enzyme ; epilepsy ; gene ; hereditary ; inherited ; motor ; myoclonus ; nerve cell ; neurological ; pneumonia ; recessive ; respiratory ; seizure ; sensorineural ; sensorineural hearing loss ; susceptibility ; syndrome ; wasting
You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).
The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.