X-linked myotubular myopathy (XLMTM) is a rare genetic disorder. This disease is quite devastating, and can uproot the routine of families affected. XLMTM is characterized by mutations in the MTM1 gene. The MTM1 gene codes for the protein myotubularin. Myotubularin is a protein that is critical for normal skeletal muscle function. Myotubularin is a lipid phosphatase, and it acts to remove a phosphate group from position 3 of phosphoinositides. Myotubularin regulates cellular processes, the filament network within the muscle cells, and is critical for proper function. XLMTM is an X-linked disease, meaning it is typically pathogenic in males. Females can be carriers of a mutated MTM1 gene, but are typically not affected. Females who do show symptoms typically present only with slight muscle weakness. This is due to the fact that females contain 2 copies of the gene, as they have two X chromosomes. The other functional MTM1 gene can make up for the deficits of the other gene.
Patients with XLMTM often have a difficult time going to diagnosis. They present at birth with very distinct symptoms, however, diagnosis of XLMTM typically starts with a muscle biopsy and confirmed with a genetic test. At birth, patients typically present with little to no muscle mass. They have weak lungs, and are often in respiratory failure shortly after birth. Before birth, patients in the womb will have excess amniotic fluid and limited fetal movement. About 80% of patients diagnosed with XLMTM experience a severe form of the disease. This is characterized by chronic ventilator dependence starting early on in childhood. Patients are unable to walk independently, and often do not reach motor milestones of children without this disease. There is a high rate of death in infancy, and those who do survive require extensive support. Patients with severe XLMTM spend 30-50% of the first year of life in the hospital. About 25% will not survive past the first year of life. Those who are discharged will require 24-hour ventilator support, feeding tubes, and tracheostomy tubes. About 85% of all XLMTM patients will require nutritional support. This disease affects 1 in every 50,000 male births. Besides the typical respiratory and muscle symptoms, patients will experience other comorbidities. Patients will often have hepatobiliary diseases, and are at higher risk for cholestasis and hepatic hemorrhage. They can also develop hepatic peliosis, which are pockets of blood in the liver. They will also have issues with vision and eyesight.
XLMTM is a very rare and devastating disease. Because of the limited knowledge about the disease, there are no current treatments or cures for the disease. Patients are often solely treated with supportive care measures. This is a huge gap in the availability of treatments for these patients. These patients, as well as their families and loved ones, deserve to have options available. No parent or loved one should have to watch their child die a slow death, and there should be hope for everyone suffering from a rare disease. There are investigational therapies in the works for XLMTM, and hopefully the treatment of this disease will look different in the next few years.
Dowling JJ, Lawlor MW, Das S. X-Linked Myotubular Myopathy. 2002 Feb 25 [Updated 2018 Aug 23]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1432/
Amburgey K, Tsuchiya E, de Chastonay S, et al. A natural history study of X-linked myotubular myopathy. Neurology. 2017;89(13):1355-1364.