Liver damage in myotubular myopathy

Hepatobiliary involvement, such as gallstones or peliosis hepatis, has been reported in several cases of myotubular myopathy since the 1990s. It was found in 7% of participants in the Recensus study or the natural  history study NatHis-MTM. 

With the death from severe hepatic insufficiency of three participants in the ASPIRO trial receiving the highest dose of AT-132, a gene therapy product providing the MTM1 gene, and then of a fourth receiving half the dose, the question crucially arises from the hepato-biliary involvement in this disease and its mechanisms. 

An Italian team collected clinical data from 12 children and adolescents with myotubular myopathy, aged 7 months to 19 years. All of them had a semi-annual clinical and laboratory assessment and a liver ultrasound each year. 

  • Eight patients presented with an intermediate form and four with a severe form of myotubular myopathy. 
  • Abnormal liver structure on ultrasound was found in 7 patients, with evidence of peliosis hepatic in two of them.
  • Transaminases were elevated in five cases.
  • Five children presented with gallstones, four of whom were asymptomatic.
  • Four participants (three less than 2 years old and one 19 years old) had no signs of hepato-biliary, ultrasound, or laboratory damage.


Hepatobiliary disease in XLMTM: a common comorbidity with potential impact on treatment strategies. D’Amico A, Longo A, Fattori F, Tosi M, Bosco L, Chiarini Testa MB, Paglietti G, Cherchi C, Carlesi A, Mizzoni I, Bertini E. Orphanet J Rare Dis. 2021 Oct 12;16(1):425.