title: Diffuse neuroaxonal involvement in mucolipidosis IV as assessed by proton magnetic resonance spectroscopic imaging.
abstract: 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.
authors.affiliation: Second Division of Neurology, Second University of Naples, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Bonavita
authors.forename: Anette
authors.initials: A
authors.lastname: Virta
authors.forename: Neal
authors.initials: N
authors.lastname: Jeffries
authors.forename: Ehud
authors.initials: E
authors.lastname: Goldin
authors.forename: Gioacchino
authors.initials: G
authors.lastname: Tedeschi
authors.forename: Raphael
authors.initials: R
authors.lastname: Schiffmann
mesh_terms: D000293:Adolescent; D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000032:analysis; D001369:Axons / Q000473:pathology*; D001923:Brain Chemistry; D002648:Child; D002675:Child, Preschool; D003401:Creatine / Q000032:analysis; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009081:Mucolipidoses / Q000175:diagnosis* / Q000473:pathology*; D010725:Phosphocreatine / Q000032:analysis
chemical_list: D010725:Phosphocreatine; D001224:Aspartic Acid; C000179:N-acetylaspartate; D003401:Creatine