Failure of Allogeneic Transplant to Correct Sialidosis Despite Early Diagnosis and Full Donor Engraftment of Non‐Carrier Leucocytes

Sialidosis, also known as Mucolipidosis Type I, is a rare condition caused by defects in the NEU1 gene which causes the accumulation of sialylated peptides, oligosaccharides, and glycoproteins leading to neurological decline. Haematopoetic stem cell transplantation has been performed in the symptomatic phase twice in the literature but has failed to prevent deterioration. We report on a case where a 4-year-old child was diagnosed with pre-symptomatic sialidosis due to investigation following the incidental detection of a cherry-red spot prior to the onset of neurological symptoms. We performed haematopoetic stem cell transplantation with a matched unrelated cord blood unit with optimal timing prior to clinical decline, achieving full donor engraftment with a largely uneventful post-transplant recovery followed by a period of relative clinical stability. However, subsequent neurological decline detailed by clinical history and radiological findings has occurred suggesting a lack of disease responsiveness to transplantation despite optimal timing. We go on to provide supporting laboratory investigations detailing sialidosis fibroblast culture as part of a novel cross-correction assay and compare results to other transplant responsive lysosomal storage disorders such as mucopolysaccharidosis type 1-H and detail a lack of cross-correction in concordance with our clinical findings. We conclude that conventional allogeneic haematopoetic stem cell transplantation is not a viable disease-modifying treatment option in sialidosis, even when performed optimally in the pre-symptomatic phase, and suggest that alternative treatment options must be explored to improve outcomes in this condition.