A recent case series published in the Annals of Indian Academy of Neurology describes four cases of adults who were diagnosed with mitochondrial DNA maintenance defects (MDMD), a group of disorders that includes thymidine kinase 2 deficiency (TK2d).
The study highlights the fact that some patients may experience nonspecific symptoms of MDMDs during childhood, leading to delayed diagnosis until later in life.
“Genetic testing is essential for diagnosis, as phenotypic variability often obscures underlying MDMD,” the authors explained.
The first patient was a 19-year-old man with childhood-onset hearing and speech impairment, along with weakness in the hands and feet. He was severely underweight at presentation, with drooping eyelids, reduced reflexes and polyneuropathy (peripheral nerve damage).
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Magnetic resonance imaging (MRI) suggested leukodystrophy, or damage to the protective sheath around nerves. Genetic testing confirmed a mutation in the TYMP gene, and the patient was diagnosed with mitochondrial neurogastrointestinal encephalomyopathy.
The next patient was a 25-year-old man experiencing significant weight loss and gastrointestinal symptoms including vomiting and pain for six months. He also had drooping eyelids, muscle wasting and absent reflexes.
Computed tomography (CT) and MRI findings were consistent with leukodystrophy, and genetic sequencing revealed a TYMP gene mutation, leading to a diagnosis of mitochondrial neurogastrointestinal encephalomyopathy.
Patient three, a 19-year-old-man with progressive muscle weakness, presented with a sudden altered mental status. He had a family history of these symptoms: His older brother had died at 13 years of age after experiencing similar symptoms.
Testing confirmed leukodystrophy and neuropathy, and the patient was found to have a mutation in the MPV17 gene. He died three weeks after admission to the hospital.
The final patient was a 22-year-old woman who had developed progressive weakness and pancreatitis one year prior. She displayed muscle wasting, reduced reflexes and neuropathy. MRI testing demonstrated concentric ring lesions, which had not been previously reported in patients with pathogenic MPV17 mutations. However, she had the same mutation as patient three.
“Our findings underscore the need for increased awareness of this delayed‑diagnosis presentation to enable timely intervention,” the researchers concluded.
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