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Beneficial effect of albuterol in congenital myasthenic syndrome with epsilon‐subunit mutations
Author(s) -
Sadeh Menachem,
Shen XinMing,
Engel Andrew G.
Publication year - 2011
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.22153
Subject(s) - congenital myasthenic syndrome , acetylcholine receptor , frameshift mutation , pyridostigmine , medicine , myasthenia gravis , mutation , acetylcholinesterase , protein subunit , compound heterozygosity , nicotinic acetylcholine receptor , endocrinology , pharmacology , chemistry , genetics , receptor , biology , enzyme , biochemistry , gene
Mutations in the epsilon subunit of the acetylcholine receptor (AChR) are a common cause of congenital myasthenic syndrome (CMS). Patients are usually treated with acetylcholinesterase inhibitors and 3,4‐diaminopyridine with modest clinical benefit. We report 2 patients with CMS due to mutations in the AChR epsilon subunit. The first patient carries two heterozygous frameshift mutations, ε127ins5 and ε1293insG. The second patient is homozygous for the εC142Y mutation that curtails AChR expression to 22% of wild‐type in HEK cells. Treatment with pyridostigmine and 3,4‐diaminopyridine had a limited beneficial effect in the first patient, and the second patient became wheelchair‐bound during therapy. The additional use of albuterol produced dramatic improvement in strength and in activities of daily living in both patients. The efficacy and safety of albuterol in patients who harbor identified low‐expressor or null mutations in the epsilon or other subunits of AChR merits a well‐designed clinical trial. Muscle Nerve, 2011