TK2D Case 2: Late-Onset Presentation, Lactate, EMG, and Muscle Biopsy

This episode, "TK2D Case 2: Late-Onset Presentation, Lactate, EMG, and Muscle Biopsy," opens with the second patient, an adult with a long, subtle history.

Dr. Hirano presents Case 2, a 34-year-old woman with a six-year history of progressive ptosis, mild dysphagia, and proximal limb weakness, diagnosed with late-onset TK2D after onset around age 28. She recalls being a slower runner than her peers by age 5. She was treated empirically for myasthenia gravis without improvement, and pulmonary function tests showed early restrictive changes. Examination showed marked facial weakness, bilateral ptosis, and proximal weakness of 4 out of 5, with normal distal strength and reflexes. CK was 300 units per liter, lactate was normal at 1.1 millimolar, and EMG showed myopathy. Biopsy revealed multiple mitochondrial DNA deletions without depletion, and testing found biallelic pathogenic TK2 variants. Management was supportive monitoring.

Dr. Zolkipli-Cunningham calls this a classic late-onset presentation. She urges clinicians to ask proactively about earlier history, such as whether the patient was a slow runner or avoided gym. The muscle involvement was always there, and short stature or a thin build may also emerge. A normal lactate should not steer clinicians away from mitochondrial disease, since it may be normal at baseline and high during illness, stress, or exercise. Multiple deletions are typical, and are helpful when justifying genetic testing or interpreting unclear results.

She asks clinicians not to stop at nonspecific histopathology. Frozen muscle is often stored in the pathology laboratory for years, and she has seen patients told they have no muscle disorder because histopathology was normal. Sequencing mitochondrial DNA in that tissue provided strong evidence. Dr. Hirano adds that community hospitals may lack special mitochondrial stains, a further reason to retrieve old muscle.

In "Adults With TK2D: Monitoring, Late-Onset Phenotype, and the Impact of Diagnosis," Dr. Zolkipli-Cunningham outlines supportive monitoring for this patient, explains how late-onset disease presents, and discusses what a diagnosis means.