UBA5 GENE & UBA5 GENE DEFICINECY
In the United States, the FDA classifies rare disease as something that affects fewer than 200,000 American citizens. In contrast, the Europeans register a disease as rare when it affects less than 1 in 2,000. Estimations are that 350 million people suffer from rare diseases in the world. Below, are a few statistics from the National Institutes of Health on rare diseases. The Rare Disease Network is another wonderful resource for information.
1 in 2 patients diagnosed with a rare disease are children.
Rare diseases impact more people than AIDs and cancer combined.
1 in 10 people are affected by rare disease.
1 in 2 rare diseases don’t have a foundation or research support group.
Do these numbers seem small? Well, consider that there are over 6,000 known rare diseases which affect around 25 million people. This represents around 10% of the U.S. population. Rare diseases bring forth many challenges in different areas. Some diseases are not well characterized or defined and very few specialized centers are exist for diagnosis, management, and research.
Now more about the UBA5 gene mutation that our son, Austin was diagnosed with. UBA5 is a gene in our body. The UBA5 gene mutation, like many other specific rare diseases, effects very few people but the fight for the entire rare disease community is enormous. Austin's rare genetic condition is called UBA5-Related Early Infantile Epileptic Encephalopathy. Genes tell the body to make many different proteins and UBA5 tells the body to make an enzyme that is involved in attaching ubiquitin to proteins.
Ubiquitin's are small proteins found in almost all cells. They are added to proteins to direct the protein for breakdown, to move to different part of the cell, to change their activity and also alter protein interactions. There are several different types of enzymes involved in getting the ubiquitin attached to the protein.
There can be changes in a gene (mutations) that cause the gene to malfunction and to not produce what the gene is supposed to make. We have 2 copies of most of our genes. If both copies have mutations that alter the function, then the body is deficient, often very deficient, in what that gene was supposed to make.
Deficiency of the UBA5 gene is rare but does occur. Since both copies of the UBA5 gene must be affected to cause problems, this is considered an autosomal recessive condition. One copy of each of the genes is inherited from the mother and one copy from the father. Each of the parents would still have 1 normal copy of the gene; the parents are carriers of the defective gene.
A child may inherit the defective copy of the gene from each parent, that child would have no normal UBA5 gene. There are distinctive clinical findings if a person has no normal UBA5 gene. These children present in early infancy with irritability, poor tone in trunk (they are floppy), and with time, increased tone in the arms and legs (spasticity). Dystonia is present and is something that affects the patients quite severely. Dystonia is an involuntary movement disorder, Involuntary movement disorders are movements that are not under the patient's control and can cause significant
disability. In addition, these patients have seizures, poor head growth, and intellectual disabilities.
All of these features taken together are a form of infantile-onset encephalopathy, or brain disease beginning in infancy, There is no known cure and current treatments simply try to treat the symptoms of the disease.
It took many years of testing to finally receive Austin's diagnosis.
Here is a breakdown of some of the genetic/blood tests he's had since 2014.
-Biotinidase & plasma amino acid - Plasma carnitine showed middle increased esterified carnitine and interestingly, has some persistent mild elevation of long-chain acylcarnitines.
-Mitochondrial DNA- Next-Generation Sequencing Panel
-Comprehensive Intellectual Disability Panel
-NexGen for long-chain fatty acid disorders
-Skin biopsy to grow for fibroblast for further investigation of the ACAD10
-Whole Exome Sequencing Test
February 2014 we started one of the most in-depth genetic test called Whole Exome Sequencing. At this time Austin. Anthony and myself all submitted our blood work for analyzing. It was found at the time there were no reported causative mutations in diseases associated with reported phenotype.
‘It is possible that this patient has a pathogenic mutation outside of the coding regions analyzed, or in a regulatory or deep intronic region that would not be detected by Whole Exome Sequencing.’ - GeneDx