The path to a diagnosis of thymidine kinase 2 deficiency (TK2d) can be long and winding. One of the many reasons for this is that the symptoms of TK2d are very similar to those of other diseases that affect nerve and muscle function.
Because of this symptom overlap, TK2d can go undiagnosed for many years. Making sure your care team is aware of this ultra-rare condition and its differential diagnoses is key to ensuring you or your children receive the proper care.
Diseases mimicking early-onset TK2d
Infantile-onset TK2d is the most severe form of the disease. Symptoms usually arise before one year of age and can progress quickly.
Spinal muscular atrophy
Spinal muscular atrophy (SMA) is a rare disease that causes progressive muscle weakness over time due to the breakdown of motor neurons in the spinal cord. Symptoms of SMA type 1 and SMA type 2 are most similar to those of early-onset TK2d.
The hallmark symptoms of SMA include:
- Weakness on both sides of the body, especially in the hips, shoulders and back.
- Tremors and trembling, which are especially prominent in SMA type 2.
- Scoliosis or other bone abnormalities.
- Difficulty breathing, chewing and swallowing.
Read more about TK2d signs and symptoms
Congenital myopathy
Congenital myopathy is an umbrella term for a group of rare, genetic muscle diseases that often arise during infancy. Patients with congenital myopathy may exhibit hypotonia, sometimes described as “floppy baby syndrome,” delayed developmental milestones and muscle weakness throughout the body.
Other mitochondrial DNA depleting disorders
There are many mitochondrial DNA depleting disorders other than TK2d that have similar symptoms. Diseases driven by mutations in the RRM2B, SUCLA2 or SUCLG1 genes can cause brain dysfunction and muscle weakness in infants, which is known as encephalomyopathy.
Pompe disease
Pompe disease is a rare disease caused by deficiencies in lysosomal acid alpha-glucosidase. Patients with the disease experience poor muscle tone and weakness, and they can develop difficulty breathing with time.
Like TK2d, Pompe disease has infantile and late-onset forms and can be a differential diagnosis of all types of TK2d. As a result, symptoms can vary significantly depending on the age of onset and how quickly the disease progresses.
Diseases mimicking childhood-onset TK2d
Symptoms of childhood-onset TK2d usually begin between 1 to 12 years of age and are often less severe than those of early-onset TK2d.
SMA type 3
SMA type 3 is a milder form of SMA that causes muscle weakness, particularly in the legs. As a result, individuals with the disease may face difficulty standing and walking. Usually, patients with this form don’t have trouble breathing and have a normal or near-normal life expectancy.
Limb-girdle muscular dystrophy
Limb-girdle muscular dystrophy (LGMD) is a group of diseases that causes progressive muscle weakness and atrophy, primarily in the hip and shoulder muscles, though other parts of the body can also be affected.
Diseases mimicking late-onset TK2d
Late-onset TK2d typically develops after 12 years of age and is the mildest form of the disease.
Chronic progressive external ophthalmoplegia
Chronic progressive external ophthalmoplegia (CPEO) causes weakness in the eye muscles and can be caused by several mitochondrial DNA depletion syndromes. Symptoms usually arise during early adulthood.
SMA type 3 and SMA type 4
SMA types 3 and 4 can cause symptoms similar to those of late-onset TK2d. SMA type 4 causes weakness in the legs and hips, but most patients are able to maintain the ability to walk throughout life.
Limb-girdle muscular dystrophy
Symptoms of LGMD can also arise later in life, mimicking late-onset TK2d.
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