Beneficial effects of albuterol in congenital endplate acetylcholinesterase deficiency and Dok‐7 myasthenia

Abstract

Background Congenital myasthenic syndromes (CMS) are disabling but treatable disorders. Anticholinesterase therapy is effective in most, but is contraindicated in endplate (EP) acetylcholinesterase (AChE) deficiency, the slow-channel syndrome, Dok-7 myasthenia, β2-laminin deficiency, and is not useful in CMS due to defects in MuSK, agrin, and plectin. EP AChE, Dok-7 and β2-laminin deficiencies respond favorably to ephedrine but ephedrine can no longer be prescribed in the US. Methods We used albuterol, another sympathomimetic agent, to treat three patients with EP AChE deficiency and 15 with Dok-7 myasthenia. Response to therapy was evaluated by a 9-point questionnaire pertaining to activities of daily life. Results Comparison of the pre- and post-treatment responses indicated a beneficial response to albuterol (p values <0.001) in both patient groups. The adverse effects of therapy were like those of ephedrine. Discussion Our observations should spur controlled prospective clinical trials of albuterol in these as well as other CMS.

Sympathetic innervation controls homeostasis of neuromuscular junctions in health and disease

“…It remains to be studied whether SM primarily improves sarcomeric function, neuromuscular transmission, or a mixture of both. Although SM is effective in some forms of myasthenic syndromes (NMJ pathology) (3,(35)(36)(37) and spinal muscular atrophy (motor neuron defect involving the NMJ) (38), it was not effective in a trial for facioscapulohumeral muscular dystrophy (primary muscle pathology) (39). In clinics, sympathectomy is used to treat hyperhidrosis.…”

Current Treatment, Emerging Translational Therapies, and New Therapeutic Targets for Autoimmune Myasthenia Gravis

“…The classic drug used in this way is pyridostigmine, which enhances neuromuscular transmission by inhibition of acetylcholinesterase, thereby prolonging the effects of acetylcholine at the neuromuscular junction. Recently, β2 adrenergic receptor agonists have been reported to provide symptomatic benefit in certain forms of congenital myasthenia [150]. The mechanism of action is not entirely clear but is believed to involve stabilization of AChRs at the postsynaptic membrane through protein kinase A (a downstream effector of β2 adrenergic receptors).…”

Clinical Reasoning: A 14-year-old boy with fatigue and episodic worsening of weakness

“…Genetic testing revealed 2 pathogenic heterozygous mutations: c.1124_1127dupTGCC and c.1378dupC in exon 7 of the Dok-7 gene. 4,10 How to treat this patient? Cholinergic agents are of uncertain benefit and can actually worsen the symptoms in Dok-7 mutation, and therefore should be avoided.…”

“…Albuterol 4 mg 1-3 times a day in adults, 2 mg 2-3 times a day in the age group of 6-12 years, and 0.1 mg/kg/d (maximum up to 2 mg) 3 times daily for children between 2 and 6 years have shown clinical response. 3,10 The patient was started on albuterol 4 mg twice a day with marked improvement in his symptoms.…”