A recent study by the National Institutes of Health (NIH) found that mitochondrial diseases such as thymidine kinase 2 deficiency account for 3% of all confirmed diagnoses in its Undiagnosed Diseases Program (UDP).
The research, published in Genetics in Medicine Open, highlights that these conditions can often remain hidden until later in life, sometimes as late as a patient’s 70s.
The Undiagnosed Diseases Program is an NIH initiative that evaluates patients with complex, unresolved medical conditions to provide diagnoses and potential treatment recommendations.
By using advanced genomic sequencing and multidisciplinary expert teams, the program identifies rare or entirely new disorders. These clinical evaluations help researchers gain new insights into genetics and the underlying mechanisms of human disease.
Mitochondrial diseases are caused by genetic changes that affect how cells produce energy. While they are typically diagnosed in children with severe, progressive symptoms, the UDP study revealed a significant number of “late-onset” cases. In many instances, these patients had been visiting multiple specialists for years to manage isolated symptoms, without anyone realizing the issues were all connected to a single mitochondrial cause.
Read more about signs and symptoms of TK2d
Since 2009, the UDP has conducted prospective clinical evaluations on nearly 1,400 participants to address complex diagnostic challenges through a systematic approach. For patients suspected of having mitochondrial issues, this process involves extensive record reviews and multidisciplinary evaluations, alongside specialized tests such as muscle biopsies to examine respiratory chain enzymology and mitochondrial DNA copy numbers.
The diagnoses identified through these methods ranged from well-known conditions like Kearns-Sayre syndrome to various mitochondrial DNA depletion syndromes (a group of disorders that includes TK2d).
Ultimately, the researchers emphasized that a comprehensive, “all-in-one” evaluation is often what is needed to solve these medical mysteries. “The UDP research provides the opportunity to complete comprehensive records reviews coupled with multidisciplinary evaluations and post admission efforts that can lead to making mitochondrial disease diagnosis for participants with atypical presentations,” the authors concluded.
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