Abstract
BACKGROUND: Limited or absent genetic counseling and testing resources in low- and medium-income countries lead to missed or late diagnoses for treatable metabolic conditions with irreversible complications. In some communities, misunderstanding about the etiology of a genetic condition may lead women whose children are affected to be viewed as a bad omen and become stigmatized or ostracized from their community. Mucopolysaccharidosis type II (MPS II), or Hunter syndrome, is a lysosomal storage disorder in which deficiency or inactivity of the enzyme iduronate-2-sulfatase leads to accumulation of glycosaminoglycans throughout the body. The diagnosis can be made through clinical assessment, enzyme activity analysis, or DNA sequencing. Treatment requires a multidisciplinary approach combining supportive care with disease-modifying therapies, including enzyme replacement therapy where available. RESULTS: To understand the incidence and impact of MPS II in Kenya, we sought to provide counseling and genetic testing to individuals and families with suspected MPS II. After pretest counseling, we collected blood from 25 individuals to determine iduronate-2-sulfatase levels and sequence the IDS gene. We identified a pathogenic or likely pathogenic variant in 17 of 25 individuals and subsequently identified 18 female carriers in these families. We catalog the genotype of males with MPS II and correlate this with the phenotypic profile of these individuals, the female carrier rate, and mortality within the families. CONCLUSIONS: This study provides the first summary of genotype-phenotype correlations for MPS II in individuals from Kenya. These findings will allow the development of guidelines to identify individuals who may benefit from early evaluation, especially in those families where there is a risk of MPS II.