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 ...
), predominantly affecting
proximal
Standard anatomical terms of location are used to unambiguously describe the anatomy of animals, including humans. The terms, typically derived from Latin or Greek roots, describe something in its standard anatomical position. This position ...
muscles, combined with
denervation and
myoclonic seizure
An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with lo ...
s. Only 12 known human families are described in scientific literature to have SMA-PME.
SMA-PME is associated with a
missense mutation
In genetics, a missense mutation is a point mutation in which a single nucleotide change results in a codon that codes for a different amino acid. It is a type of nonsynonymous substitution.
Substitution of protein from DNA mutations
Missense m ...
(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 sequen ...
2 of the ''
ASAH1''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
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 an ...
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 chromosomal 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
A lysosome () is a membrane-bound organelle found in many animal cells. They are spherical vesicles that contain hydrolytic enzymes that can break down many kinds of biomolecules. A lysosome has a specific composition, of both its membrane prote ...
. The lysosome breaks down acid ceramidase; the fatty acid component is then used to produce
myelin
Myelin is a lipid-rich material that surrounds nerve cell axons (the nervous system's "wires") to insulate them and increase the rate at which electrical impulses (called action potentials) are passed along the axon. The myelinated axon can ...
. 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 spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action p ...
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
Spinal muscular atrophies (SMAs) are a genetically and clinically heterogeneous group of rare debilitating disorders characterised by the degeneration of lower motor neurons (neuronal cells situated in the anterior horn of the spinal cord) and ...
*
Progressive myoclonus epilepsy
Progressive Myoclonic Epilepsies (PME) are a rare group of inherited neurodegenerative diseases characterized by myoclonus, resistance to treatment, and neurological deterioration. The cause of PME depends largely on the type of PME. Most PMEs are ...
References
Further reading
*
External links
{{CNS diseases of the nervous system
Systemic atrophies primarily affecting the central nervous system
Neurogenetic disorders
Autosomal recessive disorders