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Background Congenital myasthenic syndromes (CMS) are a group of inherited neuromuscular disorders caused by defects at the neuromuscular junction. The defect in choline acetyltransferase (CHAT) causes a type of presynaptic CMS characterised by hypotonia, paralysis of cranial and limb muscles, and apnea at birth. Diagnosis is based on genetic testing and electromyography. Purpose To describe the efficacy and safety of combined treatment with amifampridine and pyridostigmine in childhood presynaptic CMS. Material and methods A 4 day old newborn male with generalised hypotonia and respiratory failure needing mechanical ventilation. Physicians performed intravenous neostigmine diagnostic test showing improvement of muscle strength and ability to move. Two CHAT gene heterozygous mutations (c. 1249 G>A and c. 1505 T>C) were detected through genetic testing 4 months’ later. The first one is already linked to presynaptic CMS. Results After performing a neostigmine diagnostic test, his physicians sought treatment with oral pyridostigmine 1 mg/kg/6 hour. The hospital Pharmacy Department elaborated 4 mg hard capsules starting from pyridostigmine 60 mg tablets and maltodextrin as excipient. Dose must by reduced due to anticholinergic toxicity (oliguria and heavy sweating) several months’ later: consequently physicians added amifampridine (2 mg/6 hour) to previous treatment. Our department made compounded amifampridine capsules using raw material because of the greater cost of amifampridine 10 mg tablets. Combination therapy seemed to facilitate eye opening and limb movement. Amifampridine was better tolerated than pyridostigmine by the patient. He recived medical discarge after 3 weeks’ treatment. Conclusion The recommended treatment for presynaptic CMS is acetylcholinesterase inhibitor (pyridostigmine or neostigmine). Amifampridine has presented only as an effective treatment for some postsynaptic types of CMS. In this case, however, amifampridine was useful for symptom management and allowed acetylcholinesterase inhibitor dosage reduction. Pharmaceutical compounding is often indispensable in obtaining the exact paediatric dosages. References and/or Acknowledgements 1. Schara U, et al. Long-term follow-up in patients with congenital myasthenic syndrome due to CHAT mutations. Eur J Paediatr Neurol2010Jul;14(4):326–33. No conflict of interest |
