LAUSR

Cobalamin C (CblC) deficiency (alias methylmalonic aciduria and homocystinuria, CblC type, OMIM # 277,400) is the most common inborn error of intracellular cobalamin metabolism. The onset is usually in the first year of life [1], but occasionally it can present in adolescence or adulthood with a large spectrum of neurological and extra-neurological features, including neuropsychiatric symptoms, myelopathy/ peripheral neuropathy, thromboembolism, and kidney disease [2, 3]. CblC deficiency can be a progressive and even life-threatening disease when not promptly recognized and treated [1]. With therapy, the prognosis can be good, especially in lateonset cases [4], while if treatment is delayed, neurological sequelae are usually permanent [1, 4]. In this article, we report a case of adult-onset CblC deficiency manifesting for years as an epileptic syndrome with myoclonus. A 36 year-old man, born to non-consanguineous parents and with normal psychomotor development, was referred to our Epilepsy Centre because of a complicated, drug-resistant epileptic syndrome with myoclonus. His medical history started at the age of 18 when he had one morpheic tonic–clonic seizure (TCS), followed by recurrent jerks involving both arms suggestive of myoclonic seizures (Fig 1a). Brain MRI was unremarkable, and interictal electroencephalography (EEG) showed normal background and few spikes. Juvenile myoclonic epilepsy (JME) was suspected, and valproate was started with benefit. At age 20, valproate was stopped with no further TCSs and only occasional jerks. At age 32, he had another TCS, and levetiracetam was initiated. At age 34, he developed renal failure with estimated glomerular filtration rate reduction until 32.7 ml/min/1.73 mq (normal value> 60); renal biopsy was non-specific.[5] At age 35, he developed cognitive decline with superimposed episodes of severe confusion, progressive memory deterioration, poor speech, and insomnia. He also presented behavioural changes with social withdrawal, anxiety, kinaesthetic hallucinations, and compulsive disorder. There was a concomitant marked worsening of the frequency and severity of jerks and seizure recurrence (Fig. 1a). Given the lack of response to anti-seizure medication, he was referred to our Institute. Our neurological examination revealed bradykinesia and motor awkwardness, subtle tremor-like finger twitches, and exaggerated deep tendon reflexes, whereas neuropsychological assessment revealed moderate multi-domain dysfunction (i.e., attention, naming, verbal fluency, figure recognition, learning, long-term visual memory, praxis, and theory of mind difficulties). Brain MRI showed diffuse atrophy without leukoencephalopathy, and brain FDG-PET revealed marked hypometabolism in multiple regions (Fig. 1b, c). Neuro-ophthalmologic evaluation showed optic nerve atrophy with retinopathy. Spinal cord MRI was normal, while motor-evoked potentials of lower limbs showed central conduction time increase. EEG and magnetoencephalography showed diffuse delta waves, and simultaneous electromyography recording during the maintenance of hand extension showed repeated myoclonic Roberta Di Giacomo and Ettore Salsano have contributed equally to the present work.