Patient 1: The patient was an 18-year-old woman. At 15 years old, she complained of bilateral numbness below the knee developing from distal to proximal, aggravated by exertion and alleviated by rest. Meanwhile she felt heaviness of the legs and difficulty in walking, tremor of both hands when tying shoes or buttoning up. It is increasingly challenging for her to walk around unaided. After 3 years of onset, recurrent epileptic seizure was observed including focal seizures of right upper limb and generalized seizures. The patient’s past medical history was unremarkable except that she was inactive and easy to fall. Neurological examination revealed normal mental status and normal strength with global areflexia, minor horizontal nystagmus, pan-modality sensations diminished below the knee joint, subtle dysmetria over Heel–knee–shin testing and finger-nose test with closed eyes, lowered hands alternating movement, wide-based gait, positive Romberg test, flexor plantar responses.
Patient 2: A 46-year-old female patient suffered from numbness and weakness in bilateral lower limbs, unsteady gait, combined with bilateral ptosis and easy fatigability. These symptoms progressively aggravated and couldn’t relieved after rest. Ten years after onset, she developed slurred speech, dysphagia, frequent choking on drinking water, mile bilateral upper extremity weakness, difficulty walking and difficulty squatting. Neurological examination revealed bilateral complete ophthalmoplegia, significant ptosis, mild generalized weakness (grade 5-/5 on Medical Research Council scales) affecting facial, neck flexor, and proximal limb muscles, dysarthria, global areflexia, diminished sensations beneath the hip joint, wide-based gait, mild dysmetria with closed eyes and positive Romberg test.
Patients 3: A 45-year-old male patient was admitted to our hospital complaining of progressive bilateral ophthalmoplegia, ptosis and unsteady gait for 10 years. He also developed inarticulate speech, dysphagia, hearing loss, transient diplopia, numbness of distal limbs, and exercise intolerance. All these symptoms emerged successively with insidious onset and progressive course. On neurological examination, the upper eyelid covered the two-thirds of the pupil while the eyeball was almost fixed. His muscle strength was normal with decreased reflex and diminished sensations in glove sock distribution. Coordination and gait tests found bilateral dysmetria of the limbs with closed eyes, and wide-based gait.
Methods
Three patients with POLG-A were reported in detail. Their core feature was ataxia accompanied by peripheral neuropathy with or without ocular muscle weakness or epilepsy. Informed consents were obtained from the patients. Medical records were reviewed including demographic data, age at time of event, clinical history and manifestations, therapies, and follow-up. All the patients underwent a comprehensive laboratory examination for blood biochemistry, metabolic surveys including serum lactic acid and creatine kinase, routine investigations of cerebral spinal fluid (CSF), cranial and spinal MRI, electromyography (EMG), nerve conduction velocity (NCV), electroencephalogram (EEG). Next generation sequencing-based molecular study of the whole exome was performed using DNA isolated from the white blood cells. The interpretation of sequence variants was based on the American College of Medical Genetics and Genomics (ACMG) guidelines. Only Patient 2 had done muscle biopsy for light microscopic examination with histochemical and immunohistochemical stains.
All the patients took oral medications after the diagnosis, including but not limited to coenzyme Q10, vitamin C, vitamin B1, vitamin B2, and L-carnitine. Follow-up data was collected for at least 10 years.