TK2d, short for Thymidine Kinase 2 Deficiency, is a mitochondrial disease caused by inherited mutations in the TK2 gene. Thymidine kinase 2 is produced by this gene and plays a crucial role. The role of this enzyme is crucial as it helps maintain the quantity and quality of mitochondrial DNA (mtDNA) within cells. However, when mutations occur in the TK2 gene, it leads to reduced levels of thymidine kinase 2. Consequently, this deficiency results in mitochondrial DNA depletion and the occurrence of deletions within cells. These molecular changes contribute to the development and progression of TK2d.
Symptoms of TK2d:
The symptoms of TK2d primarily manifest in muscle-related impairments. The initial signs often include weakness in the limbs, as well as weakness in the muscles involved in swallowing and respiration. The specific symptoms may vary depending on the subtype of the disease.
Additional symptoms that may be present in the early-onset variant of TK2d include epilepsy, heart issues, kidney complications, and multiple bone fractures. In the childhood and late-onset variants, individuals may experience difficulty or inability to move their eyes, drooping eyelids, respiratory challenges, and hearing impairment.
Treatments for TK2d:
While there is no cure for TK2d, various treatments can help manage the manifestations and improve the quality of life for affected individuals. The treatment options for TK2d include:
Gastrostomy Tube: A gastrostomy tube may be recommended for individuals experiencing feeding difficulties, ensuring adequate nutrition.
Chest Physiotherapy: Chest physiotherapy techniques can help manage respiratory problems commonly associated with TK2d.
Ventilators: Non-invasive or invasive ventilators may be used to support respiratory function in individuals with TK2d.
Physical and Occupational Therapy: Maintaining mobility and improving muscle strength can be achieved through the utilization of physical and occupational therapy programs.
Assistive Devices: The use of assistive devices such as canes, walkers, or wheelchairs may be beneficial, depending on the degree of muscle weakness.
Cochlear Implants: For individuals experiencing hearing loss, cochlear implants can be considered to improve hearing abilities.
Anti-epileptic Medications: Anti-epileptic medications may be prescribed to manage seizures in individuals with TK2d.
Families affected by TK2d are advised to seek genetic counseling, as the disorder can be passed down through generations. Genetic counselors can offer valuable information and assistance to families concerning the chances of transmitting the condition. Furthermore, there have been encouraging outcomes in terms of survival and motor skills improvement among individuals with TK2d through experimental treatments involving deoxythymidine (dThd) and deoxycytidine (dCyt). Currently, these treatments are accessible on a restricted scale through open-label compassionate use and clinical trials in the United States and European Union.
UMDF’s Efforts in Addressing TK2d:
The United Mitochondrial Disease Foundation (UMDF) plays a vital role in advancing research, providing support, and advocating for individuals affected by TK2d and other mitochondrial diseases. UMDF has undertaken several significant initiatives, including:
Research & Funding: In the quest to discover treatments for mitochondrial diseases such as TK2d, UMDF has allocated more than $15 million toward research funding. Furthermore, through their advocacy endeavors, UMDF has successfully obtained an extra $55 million in federal funding from the Department of Defense and the National Institutes of Health.
Data: UMDF played a leading role in introducing patient registries to the mitochondrial disease community, enabling the gathering of valuable data. The next-generation patient registry, mitoSHARE, continues to contribute to the understanding of mitochondrial diseases and the development of potential treatments.
Patient Support: UMDF provides crucial support and education to thousands of families affected by mitochondrial diseases, including TK2d. Support meetings and disease-specific support groups are organized annually, fostering a sense of community and sharing of experiences.Clinician Support: UMDF conducts various initiatives to educate clinicians about mitochondrial diseases. Clinicians are provided with resources and educational opportunities such as Monthly Bench to Bedside clinician seminars, the annual Mitochondrial Medicine Symposium, the Mitochondrial Care Network, and the Mito U platform.