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 loss (
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), malnutrition, poor nourishment, poor circulatory system, circulation, loss of hormone, ...
), 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 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 sequence ...
2 of the ''
ASAH1''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
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 Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...
manner. SMA-PME is closely related to a lysosomal disorder disease called
Farber lipogranulomatosis. As with many
genetic disorder
A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosome abnormality. Although polygenic disorders ...
s, there is no known cure for SMA-PME.
The condition was first described in 1979 by American researchers
Joseph Jankovic and Victor M. Rivera.
ASAH1 gene
The ASAH1 gene codes for
acid ceramidase, 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
An axon (from Greek ἄξων ''áxōn'', axis) or nerve fiber (or nerve fibre: see American and British English spelling differences#-re, -er, spelling differences) is a long, slender cellular extensions, projection of a nerve cell, or neuron, ...
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
Spinal muscular atrophy
Autosomal recessive disorders