Biochemical and clinical response after umbilical cord blood transplant in a boy with early childhood‐onset beta‐mannosidosis

Abstract

Background Deficiency in the enzyme β‐mannosidase was described over three decades ago. Although rare in occurrence, the presentation of childhood‐onset β‐mannosidase deficiency consists of hypotonia in the newborn period followed by global development delay, behavior problems, and intellectual disability. No effective pharmacologic treatments have been available. Methods We report 2‐year outcomes following the first umbilical cord blood transplant in a 4‐year‐old boy with early childhood‐onset disease. Results We show restoration of leukocyte β‐mannosidase activity which remained normal at 2 years posttransplant, and a simultaneous increase in plasma β‐mannosidase activity and dramatic decrease in urine‐free oligosaccharides were also observed. MRI of the brain remained stable. Neurocognitive evaluation revealed test point gains, although the magnitude of improvement was less than expected for age, causing lower IQ scores that represent a wider developmental gap between the patient and unaffected peers. Conclusion Our findings suggest that hematopoietic cell transplant can correct the biochemical defect in β‐mannosidosis, although preservation of the neurocognitive trajectory may be a challenge.

Association between plasma proteome and childhood neurodevelopmental disorders: A two-sample Mendelian randomization analysis

“…Deficiency in MANBA is associated with hypotonia in the newborn, followed by global development delay, behavioral problems, and intellectual disability. 56 , 57 Beta-mannosidosis is a disorder characterized by the accumulation of disaccharides resulting from insufficient lysosomal MANBA activity. Sedel et al.…”

Beta‐mannosidosis presenting predominantly with recurrent pulmonary infections, hemorrhage, and cystic lesions

“…Pulmonary hemorrhage is secondary to the fungal infection as it may relieve after infection controlled. The only possible radical cure for β‐mannosidosis today is hematopoietic stem cell transplantation, which can correct the biochemical defect, according to the report 3 . However, neurological damage is still a problem.…”

“…The only possible radical cure for β-mannosidosis today is hematopoietic stem cell transplantation, which can correct the biochemical defect, according to the report. 3 However, neurological damage is still a problem. Histological modifications were observed in the tissues of goats, including important neuronal vacuolation, myeline deficiency, eosinophilic spheroids in white fibers, vacuolization of hepatocytes, lung, and pancreatic cells.…”

The Role of Hematopoietic Cell Transplant in the Glycoprotein Diseases

“…Only one known HCT has occurred in a patient with β-mannosidosis [ 46 ]. HCT was performed for a 4-year-old boy who was diagnosed after presenting with macrocephaly and gross motor delays including deficits in balance and gait.…”

“…The patient achieved engraftment, near normal CSF and plasma enzyme levels, and displayed a dramatic drop in urine oligosaccharides following HCT. At 2 years post-HCT, the patient had persistent impairment in motor function and a decline in visual/motor integration, memory, and overall IQ [ 46 ]. The limited experience with HCT in this disease suggests that the peripheral biochemical defect can be corrected with successful donor engraftment, but the extent of overall musculoskeletal and neurocognitive benefits have yet to be fully realized.…”