Mucopolysaccharidosis Type II: One Hundred Years of Research, Diagnosis, and Treatment

Int J Mol Sci. 2020 Feb 13;21(4):1258. doi: 10.3390/ijms21041258.

PMID: 32070051

Francesca D'Avanzo, Laura Rigon, Alessandra Zanetti, Rosella Tomanin

Highlights: This review summarizes the history of Mucopolysaccharidosis type II (MPS II, Hunter syndrome) through clinical and laboratory evaluations that allowed its correct diagnosis, pathogenesis, and therapeutic protocols. The main issues are also highlighted related to the possible newborn screenings for MPS II, brain pathogenesis, and treatment of the neurological compartment.

Abstract

Background: Mucopolysaccharidosis type II (MPS II, Hunter syndrome) was first described in 1917 by Dr. Charles Hunter. Hunter syndrome was initially disregarded for a few decades and subsequently confused for a long time with the similar disorder Hurler syndrome. Hunter syndrome has been clearly separated as a unique disease since 1978, when the distinct genetic causes of the two disorders were eventually found. MPS II is the only X-linked-inherited mucopolysaccharidosis. It is a rare genetic disease with an incidence rate ranging from 0.38 to 1.09 per 100,000 live male births, according to recent research. The lysosomal hydrolase iduronate 2-sulphatase, which is a key enzyme in the stepwise breakdown of heparan and dermatan sulphate, is deficient in this disorder. In at least two-thirds of patients, this results in a severe clinical phenotype affecting most organ systems, including the brain.

Objective: This review summarizes the history of the disease during this century through clinical and laboratory evaluations that allowed its definition, its correct diagnosis, a partial comprehension of its pathogenesis, and the proposition of therapeutic protocols. The main issues are also highlighted related to the possible inclusion of MPS II in newborn screenings, the comprehension of brain pathogenesis, and treatment of the neurological compartment. K

Keywords: Hunter syndrome, Mucopolysaccharidosis type II, X-linked trait; diagnosis, glycosaminoglycans, lysosomal storage disorders, pathogenesis.