Diffuse neuroaxonal involvement in mucolipidosis IV as assessed by proton magnetic resonance spectroscopic imaging.

Mucolipidosis IV is an autosomal recessive disorder caused by mutations in MCOLN1, which codes for mucolipin, a transient receptor potential protein. In order to investigate brain metabolic abnormalities in mucolipidosis IV, we studied 14 patients (11 children, 3 adults) by proton magnetic resonance spectroscopic imaging. The ratios of N-acetylaspartate/ creatine-phosphocreatine and N-acetylaspartate/choline-containing compounds in patients with mucolipidosis IV were significantly reduced in all regions of interest except the parietal gray matter and thalamus. The ratios of choline-containing compounds/creatine-phosphocreatine was not significantly reduced in patients compared with controls. The ratio of N-acetylaspartate/creatine-phosphocreatine were significantly lower (P = .005) in the more neurologically impaired patients compared with the least impaired. For every region of interest, except for parietal gray matter, the ratio of N-acetylaspartate/creatine-phosphocreatine was lower in the more motorically impaired patient group. There was no difference for the ratio of N-acetylaspartate/creatine-phosphocreatine between younger and older patients. These findings suggest that mucolipidosis IV is largely a static developmental encephalopathy associated with diffuse neuronal and axonal damage or dysfunction. Mucolipin deficiency impairs motor more than sensory central nervous system pathways.