MYORG

MYORG is a glycosidase enzyme that was first studied for its role in myogenesis (muscle formation), where it may influence cell growth and signaling pathways such as those involving insulin-like growth factor 2 (IGF2).^[5] However, its relevance to disease is primarily linked to its function in the brain.

In the central nervous system, MYORG is highly expressed in S100B-positive astrocytes, a type of support cell that helps maintain the brain’s environment and supports neurons.^[12][13] This suggests that MYORG plays an important role in supporting the neurovascular unit, which regulates interactions between brain cells and blood vessels.

Biochemical studies indicate that MYORG functions as an α-galactosidase-like enzyme, helping to process specific sugar molecules (glycans) within the cell’s secretory pathway. Its activity appears to be limited to a narrow range of substrates, and its full set of natural targets is still being investigated.^[11]

Evidence from patients, experimental models, and gene expression studies indicates that MYORG is important for maintaining a stable environment in the brain. When MYORG does not function properly, this balance may be disrupted, contributing to abnormal calcium deposition around small blood vessels—a key feature of primary familial brain calcification.^[7][12][13]

Loss-of-function variants in MYORG are a major cause of autosomal recessive primary familial brain calcification (PFBC), sometimes termed MYORG-related PFBC.^{[7][8][9][10]} This disorder is characterized by abnormal deposits of calcium in the brain, most commonly affecting the basal ganglia, thalamus, dentate nuclei, and other regions visible on neuroimaging.^{[7][8][9][10]} Affected individuals often develop neurological symptoms such as movement disorders, dysarthria (difficulty speaking), and cerebellar ataxia (problems with coordination and balance). Some individuals may also experience cognitive decline or psychiatric symptoms.^{[7][8][9][10]} Unlike some other forms of PFBC, MYORG-related PFBC is inherited in an autosomal recessive pattern, meaning that affected individuals typically have two nonfunctional copies of the gene. It differs from autosomal dominant forms linked to genes such as SLC20A2, PDGFRB, PDGFB, and XPR1.^[8][9][10] Routine blood tests in people with MYORG-related PFBC usually show normal levels of calcium, phosphate, and parathyroid hormone. This indicates that the condition is not caused by a general problem with calcium metabolism, but rather by processes within the brain itself.^[8][9][10] The condition can vary in severity and age of onset. While many cases appear in adulthood, earlier onset in childhood has also been reported. Additional findings may include involvement of the brainstem, such as lesions in the pons, and a variable rate of progression over time.^{[8][9][13][10]}