Spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME), sometimes called Jankovic–Rivera syndrome, is a very rare
neurodegenerative disease whose symptoms include slowly progressive muscle (
atrophy
Atrophy is the partial or complete wasting away of a part of the body. Causes of atrophy include mutations (which can destroy the gene to build up the organ), poor nourishment, poor circulation, loss of hormonal support, loss of nerve supply t ...
), predominantly affecting
proximal muscles, combined with
denervation and
myoclonic seizures. Only 12 known human families are described in scientific literature to have SMA-PME.
SMA-PME is associated with a
missense mutation (c.125C→T) or
deletion
Deletion or delete may refer to:
Computing
* File deletion, a way of removing a file from a computer's file system
* Code cleanup, a way of removing unnecessary variables, data structures, cookies, and temporary files in a programming language
* ...
in
exon
An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequen ...
2 of the ''
ASAH1''
gene and is inherited in an
autosomal recessive
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...
manner. SMA-PME is closely related to a lysosomal disorder disease called
Farber lipogranulomatosis
Farber disease (also known as Farber's lipogranulomatosis, acid ceramidase deficiency, "Lipogranulomatosis", and ''ASAH1''-related disorders) is an extremely rare, progressive, autosomal recessive lysosomal storage disease caused by a deficiency ...
. As with many
genetic disorders, there is no known cure for SMA-PME.
The condition was first described in 1979 by American researchers
Joseph Jankovic
Joseph Jankovic is an American neurologist who is a professor in neurology at Baylor College of Medicine in Houston, Texas. He is the Distinguished Chair in Movement Disorders and founder and director of the Parkinson's Disease Center and Moveme ...
and Victor M. Rivera.
ASAH1 gene
The ASAH1 gene codes for
acid ceramidase
The ASAH1 gene encodes in humans the ''acid ceramidase'' enzyme.
Function
This gene encodes a Heterodimeric#Biochemistry, heterodimeric protein consisting of a nonglycosylated alpha subunit and a Glycosylation, glycosylated beta subunit that i ...
, an enzyme found in
lysosomes. The lysosome breaks down acid ceramidase; the fatty acid component is then used to produce
myelin. Myelin is an insulating coating around the neurons in the body which helps to contain bioelectrical signals along a nerve cell's
axon and increase transmission rate.
In patients with SMA-PME, the ceramidase function decreases to 33.33% effective.
The lack of myelin resulting from the lack of acid ceramidase breakdown leads to nerve cell dysfunction.
See also
*
Spinal muscular atrophies
*
Progressive myoclonus epilepsy
References
Further reading
*
External links
{{CNS diseases of the nervous system
Systemic atrophies primarily affecting the central nervous system
Neurogenetic disorders
Autosomal recessive disorders