A Salbutamol responsive myopathy

Abstract

Background: Reversibility of weakness is rare in inherited muscle disease and suggests a channelopathy as the underlying pathology. Improvement in muscle strength after treatment with beta-adrenergic agonists has been documented in hyperkalaemic periodic paralysis and only very recently in the congenital myasthenic syndromes. The exact mechanism of action is not understood. Case description: Case A, the second youngest of 10 siblings from a non-consanguineous Irish kindred, presented at the age of 46 years with mild limb-girdle muscle weakness with no other symptoms and no demonstrable fatiguability. Three siblings were similarly affected (2/3 were examined, 1/3 died before examination from unrelated causes). Case B and C reported first symptoms aged 62 and 45 respectively. All 3 remained independently mobile with a waddling gait after follow up of between 11 and 25 years from first symptoms. Case A reported marked improvement in function after a short course of inhaled Salbutamol prescribed by his GP. On oral Salbutamol treatment limb-girdle strength returned to MRC grade 5, but deteriorated to MRC grade 4 when treatment was stopped. The other siblings showed similar response. Results: Initial investigation of cases A and B revealed slightly elevated creatinine kinase (CK: 307; CK:283) and some fibre atrophy and type II predominance on muscle biopsy. Case B showed 16% decrement on repetitive nerve stimulation but the others had no abnormality on neurophysiological examination. Homozygous c.1143dupC mutations in exon of the DOK7 gene were found in all three affected cases confirming a Dok-7 congenital myasthenic syndrome. Discussion: The Dok-7 CMS phenotype is that of a predominantly limb-girdle muscle weakness and a characteristic waddling gait; fatiguability may be very subtle and so these cases may be mistaken for congenital myopathy. The serendipitous prescription of Salbutamol was the clue to a myasthenic pathology in this kindred. Dok-7 CMS has been reported with adult onset but 62 years is the latest reported age at onset to date.