Long-term follow-up of metachronous marrow-kidney transplantation in severe type II sialidosis: what does success mean?

Sialidosis is a rare lysosomal storage disorder, characterizedbydeficient lysosomalneuraminidase (NEU1) activity and aberrant accumulation of sialylated glycoconjugates [1]. Affected sialidosis patients are divided into two groups [1,2]. Type I (normomorphic) sialidosis, an attenuated non-neuropathic form of the disease, is associated with cherry-red spot myoclonus syndrome, occurring in the second decade of life, and progressively impaired vision. Type II (dysmorphic) sialidosis, the severe, neuropathic form, comprises two subtypes based on the age of onset and the clinical severity: early infantile severe type—with a possible congenital or antenatal (hydropic form) onset—and late infantile or juvenile (onset after 1 year of age) type. All patients with type II sialidosis eventually demonstrate a progressive mucopolysaccharidosis (MPS)-like phenotype, including cherry-red spot myoclonus, coarse facies, visceromegaly, dysostosis multiplex, and severe mental retardation due to rapidly progressive encephalopathy [1–3]. Patients with congenital type II sialidosis present with hydrops foetalis, neonatal ascites, or both; these patients are either stillborn or die shortly after birth [1]. Within the first years of life, a few type II sialidosis patients develop a nephropathy related to kidney storage. Such a phenotype was named ‘nephrosialidosis’. To date, treatment options for sialidosis remain limited and are directed primarily at supportive care and symptomatic relief. Bone marrow transplantation (BMT) has been widely used with success in Hurler’s disease [3] before onset of severe neurological impairment, but no sialidosis patient treated by BMT has ever been published. We report the clinical outcome and long-term follow-up of a unique sialidosis type II patient who underwent metachronous marrow-kidney transplantation. We also compare this patient with the other nephrosialidosis patients reported in the literature and propose several hypotheses in order to explain BMT inefficiency in preventing renal involvement.