Novel phenotypical and biochemical findings in mucolipidosis type II

ABSTRACT: Mucolipidosis type II (ML II) is a rare lysosomal storage disorder caused by deficiency of the UDP-GlcNAc:N-acetylglucosamine-1-phosphotransferase enzyme, which catalyzes the synthesis of the mannose-6-phosphate (M6P) targeting signal for lysosomal acid hydrolases. This deficiency hinders lysosomal enzyme trafficking, impairing cellular degradation processes. Owing to its low prevalence, information on this condition is limited. We characterized the clinical, biochemical, and proteomic profiles of three patients with ML II, each harboring pathogenic GNPTAB variants identified through whole-exome sequencing (WES). Biochemical profiling consisted of urinary glycosaminoglycan (GAG) quantification and enzyme activity analysis in dried blood spots (DBS). revealing significantly elevated levels of acid sphingomyelinase, α-iduronidase, iduronate-2-sulfatase, α-N-acetylglucosaminidase, and β-glucuronidase, and supporting its utility for early diagnosis both in neonates and in older patients. Proteomic data supported these findings, highlighting disrupted biochemical pathways, including dermatan sulfate and heparan sulfate degradation and cholesterol trafficking. In ML II it is now possible to detect the pathology with enzymatic tests for acid sphingomyelinase and α-iduronidase, (or another enzymes iduronate-2-sulfatase, α-N-acetylglucosaminidase, and β-glucuronidase) the values of these enzymes will always be very high.

INSTRUMENT(S): TripleTOF 6600

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood

DISEASE(S): Mucolipidosis Ii Alpha/beta

SUBMITTER: Susana Bravo  

LAB HEAD: Susana B Bravo

PROVIDER: PXD060270 | Pride | 2025-05-07

REPOSITORIES: Pride