X-Linked Myotubular Myopathy Clinical Improvement by Use of Pyridostigmine in an Infant

Case Study: Centronuclear myopathies belong to the group of congenital myopathies. The X-linked myotubular myopathy (XLMTM) is the most common form caused by mutations in the MTM1 gene. In affected males, first symptoms of the classical type usually started postnatally with severe weakness, muscle hypotonia, feeding difficulties, and respiratory failure. The boys mostly die in the first year of life. Survivors develop a milder intermediate type and are lifelong respirator depended.

The histopathological cause of XLMTM is a delayed maturation of muscle fibers, which subsequently leads to modifications in the neuromuscular junctions resulting in disturbances in neurotransmission with clinical features similar to severe myasthenic symptoms. Only a few case reports have demonstrated a positive effect of pyridostigmine in children and adults so far.

Decreased fetal movements and polyhydramnion were already noticeable during pregnancy. He was severely hypotonic and showed general weakness. A narrow head, ptosis, ophthalmoplegia, and a high-arched palate were remarkable. Because of the respiratory failure, he was supported by intensive care and mechanical ventilation via tracheostoma. At the age of 3 months, the diagnosis of XLMTM could be confirmed by muscle biopsy; genetic analysis revealed a mutation in the MTM1 gene. Therapy with pyridostigmine was initiated at 3 months of age with a maximum dose of 1.5 mg/kg/d; a higher dose was not tolerated due to hypersalivation. Strength, range of movement, as well as the respiratory situation clearly improved under medication. Now, at the age of 13 months, the boy is able to turn onto his sides and almost in prone position. He currently needs supportive ventilation at night and during infections.

Conclusion: Because of the fact that some promising reports of single patients are available, a medical treatment with pyridostigmine seems also to be justified in young infants with XLMTM. Whether the medication alone or the natural course of the disease is responsible for the positive development of our patient remains to be seen.

Keywords: XLMTM1, pyridostigmin.