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RARE DISEASE

UBA5 GENE MUTATION

In the United States, the FDA classifies rare diseases as something that affect fewer than 200,000 American citizens. In contrast, 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 diseases.

  • 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 that affect around 25-30 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 exist for diagnosis, management, and research.

  • Check out the organization leading the charge for rare disease advocacy in the United States. National Organization for Rare Disorders. NORD's motto “Alone we are rare, together we are strong” exemplifies the mindset of the organization and some of the goals of its programs.

  • Global Genes - You’re not alone. When you’re here, you’re part of a globally connected community committed to eliminating the challenges of rare disease. Global Genes is committed to providing information, resources, and connections to all communities affected by rare diseases.

 

Now more about the UBA5 gene mutation our son, Austin was diagnosed with. February 2014 we started one of the most in-depth genetic tests called Whole Exome Sequencing. At this time Austin, Anthony, and Lindsey all submitted our blood work for analysis. It was found at the time there were no reported causative mutations in diseases associated with the 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

 

UBA5 is a gene in our body. The UBA5 gene mutation, like many other specific rare diseases, affects 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.

Ubiquitins are small proteins found in almost all cells. They are added to proteins to direct the protein for breakdown, to move to different parts 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 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 the 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. 

 

Our friends at the Raiden Science Foundation have done amazing work for the UBA5 Gene Mutation. To check out their impact on this ultra-rare disease, visit www.raidenscience.org/uba5

 

It took many years of testing to finally receive Austin's diagnosis in 2017.

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