Bone marrow transplant for a boy with alpha-mannosidosis illustrates a family’s decision-making in rare diseases

Abstract : Decision making regarding treatment of rare diseases can pose a unique challenge given the limited availability of evidence. Here we present a case of a Caucasian male who was diagnosed at age 5 years with alpha-mannosidosis, an autosomal recessive lysosomal disorder of glycoprotein metabolism, suspected based on signs of sensorineural hearing loss and apparent skeletal malformation (thickening of the cranial vault and frontal bossing, bone hyperplasia causing facial coarsening, pectus carinatum and hypertelorism). Diagnosis was confirmed based on deficient leucocyte alpha-mannosidase activity (15.5 nmol/hr/mg protein, normal range 245-625), and molecular analysis of the MAN2B1 gene, which revealed c.384G>A (p.W128X) and c.2248C>T (p.R750W) mutations. Parents made use of social media and other Internet resources to educate themselves and connect with experts and other parents of children with alpha-mannosidosis to aid decision-making regarding treatment. In 2009, the patient underwent matched sibling allogeneic bone marrow transplantation from a heterozygous carrier sibling donor, which resulted in normalization of leuococyte alpha-mannosidase activity and significant improvements in hearing, coordination and motor skills, cognitive abilities, and brain pathology. The ability of digital media and use of new technologies linking patients, their families and care-providers in decision-making networks for rare diseases is discussed.