Myasthenia gravis coexisting with HINT1-related motor axonal neuropathy without neuromyotonia: a case report

Abstract

Background HINT1 mutations cause an autosomal recessive axonal neuropathy with neuromyotonia. This is a first case report of coexistence of myasthenia gravis (MG) and HINT1-related motor axonal neuropathy without neuromyotonia. Case presentation A 32-year-old woman presented with recurrent ptosis for 8 years, diplopia for 2 years and limb weakness for 1 year and a half. Neostigmine test, elevated AChR antibody level and positive repetitive nerve stimulation supported the diagnosis of MG. Electroneurography (ENG) and electromyography (EMG) examinations revealed a motor axonal neuropathy without neuromyotonic or myokymic discharges. Next-generation sequencing and Sanger sequencing were performed to identify the gene responsible for suspected hereditary neuropathy. Genetic testing for a HINT1 mutation was performed and revealed a homozygous mutation at c.278G>T (p. G93V). The patient was treated with pyridostigmine, oral prednisolone and azathioprine. Her ptosis and diplopia have significantly improved at 6-month follow-up. Conclusions Concurrence of MG and hereditary motor axonal neuropathy without neuromyotonia is quite rare. Detection of ptosis with or without ophthalmoplegia, distribution of limb weakness, and reflex can help in recognizing the combination of MG and peripheral neuropathy. Early diagnosis is important for initial treatment and prognosis. The novel homozygous variant c.278G>T(p.G93V) contributes to the pathogenic variants spectrum of the HINT1 gene.

HINT1 neuropathy: Expanding the genotype and phenotype spectrum

“…10 To date, 128 patients with ARAN-NM have been described (108 families) worldwide. [11][12][13][14][15] Most of them are from eastern Europe, where the founder variant (c.110G>C, p.Arg37Pro) is mainly represented allele frequency 0.00043 in the European (Non-finish) population (gnomAD V3.1.2), 0.002 in Russia. 15 In addition, another founder variant (c.112T>C, p.Cys38Arg) has been identified in the Chinese population.…”