Congenital Myasthenic Syndrome with ALG2 Mutation Presenting as Progressive Ascending Paralysis: A Case Report

Aims and background: Congenital myasthenic syndromes (CMSs) are a heterogeneous group of disorders characterized by impaired neuromuscular transmission due to genetic defects in endplate proteins, particularly involving glycosylation pathways.Congenital myasthenic syndrome severity varies from mild symptoms to progressive weakness and respiratory crises, often misdiagnosed as acquired conditions.We report a rare case of ALG2-related CMS mimicking Guillain-Barr syndrome (GBS).Case description: A 10-year-old girl presented with a 5-day history of fever, followed by ascending limb weakness and respiratory distress.She had areflexia, slurred speech, and ptosis.A similar episode occurred 3 years prior, and her elder sibling had died following a similar illness.She was initially treated as GBS with intravenous immunoglobulin (IVIG) and steroids without improvement.Whole exome sequencing ultimately revealed a homozygous ALG2 mutation, confirming CMS14 (CDG type Ii).Pyridostigmine led to partial ptosis improvement but no significant respiratory recovery.She remained ventilator-dependent and succumbed after 5 months from ventilator-associated pneumonia.Conclusion: Congenital myasthenic syndrome can mimic acute flaccid paralysis and should be considered in atypical, treatment-refractory neuromuscular presentations.Early diagnosis can guide specific therapy and alter outcomes.Clinical significance: Early recognition of CMS, especially ALG2-associated subtypes, allows for initiation of targeted therapies such as pyridostigmine or combination regimens, potentially improving prognosis and preventing fatal complications.