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.

The mucopolysaccharidoses are a heterogeneous group of lysosomal storage disorders caused by deficiencies of enzymes involved in degradation of glycosaminoglycans. This study aimed to share our experience with biochemical investigations of these disorders under resource-limited conditions. Harmine extract was obtained from Peganum harmala seeds, and chromatography plates were homemade. Biochemical analysis involved urinary tests, including the Berry Spot test, the quantification of the glycosaminoglycans, as well as their characterization, and the analysis of deficient enzymes. The reference range values of glycosaminoglycans and activities of seven lysosomal enzymes, six of which are associated with these disorders were initially determined in samples of healthy subjects. The assay for β-galactosidase was described. These biochemical markers were then, evaluated in 29 patients, including 23 who were suspected of having different types of mucopolysaccharidoses and six who were diagnosed with the type I and undergoing enzymotherapy. The reference values of glycosaminoglycans and enzymes activities align with those reported in the literature. The reference value of β-galactosidase ranges from 83 to 311 nmol/17 h/mg. All the studied patients have shown the same positive pattern of Berry Spot Test in contrast of the healthy subjects. The level of GAGs was elevated by 1.1 to more than six fold but is decreased by more than six fold in patients with mucopolysaccharidosis type 1 undergoing enzymotherapy. The patients were categorized as follows: Hurler syndrome 34 %, Hunter syndrome 7 %, Sanfilippo syndrome 17 %, and Morquio syndrome 41 %. In patients for whom molecular defects were characterized, the mutations were correlated with the biochemical markers.

The aim of this study is to report a case of bilateral foveal cysts in MPS I-H resolving with oral acetazolamide and to highlight the diagnostic value of multimodal retinal imaging and electrophysiological testing. Hurler syndrome (mucopolysaccharidosis Type I-H) is a lysosomal storage disorder that can cause progressive multisystem complications. Retinal involvement often mimics retinitis pigmentosa (RP), and pathology may progress even after early hematopoietic stem cell transplantation (HSCT) due to limited enzyme penetration into ocular tissues. A 17-year-old female with MPS I-H, post-HSCT at 21 months, presented with bilateral visual decline despite a normal clinical fundus exam. Evaluation included spectral-domain OCT (SD-OCT), fundus autofluorescence (FAF), multifocal electroretinography (mfERG), full-field ERG (ffERG), and visual evoked potential. SD-OCT revealed bilateral intraretinal foveal cysts without leakage on fluorescein angiography. FAF showed a bull's eye maculopathy pattern; mfERG showed bilateral macular dysfunction. ffERG revealed rod-cone dystrophy. Two 3-month courses of oral acetazolamide (125 mg three times daily) led to complete cyst resolution and visual improvement. This case supports the role of systemic carbonic anhydrase inhibitors in treating nonleaking macular cysts in MPS I, similar to RP-related cystoid macular pathologies, and highlights the value of integrating electrophysiological and multimodal imaging, especially in occult retinal disease.

Scheie syndrome is a mild variant of mucopolysaccharidosis type I (MPS I), a rare group of lysosomal storage diseases that affect multiple organ systems. It is rarely associated with neoplasia. To the best of our knowledge, only a single case of mucopolysaccharidosis associated with a brain tumor has been reported, and it was nearly three decades ago. We present the case of a 10-year-old female with Scheie syndrome associated with a brain tumor. Physical and laboratory findings were suggestive of Scheie syndrome. A skeletal survey also revealed a spectrum of dysostosis multiplex supporting MPS. Children with MPS can have rapidly enlarging head sizes due to hydrocephalus, but our patient had several red flags that demanded further evaluation. A brain MRI revealed a mass in the fourth ventricle and a biopsy of the mass revealed pilocytic astrocytoma grade 1. Intraventricular pilocytic astrocytoma itself is a rare occurrence, accounting for only 4%-15.6 % of all pilocytic astrocytomas. Altered mucopolysaccharide metabolism can be involved in tumor pathogenesis, but the exact mechanism is unknown. Mucopolysaccharidoses, being a group of complicated disorders, are difficult to manage, and many symptoms can be missed in children due to intellectual disability. This case highlights the importance of suspecting brain tumors in children with mucopolysaccharidoses who present with signs and symptoms of increased intracranial pressure. Prompt diagnosis and management can save the child from dire neurological consequences.

A 12-year-old girl with mucopolysaccharidosis (MPS) type I (Gurler-Scheie syndrome, Q70X/del C683 of the IDUA gene in the compound heterozygous state) regularly received enzyme replacement therapy (laronidase) since the preclinical stage (6 months old) due to positive family history, and started etanercept treatment due to progression of joint pain and decreasing capability to walk. The patient had a significant reduction of pain in the joints and an expansion of daily physical activity without adverse events. A decrease in bone marrow edema without foci progression compared to baseline assessment was observed in the whole-body MRI.During the treatment (baseline/6 months/12 months) the following was observed: childhood health assessment questionnaire (CHAQ) index of 1.88/2.13/1.63 points; patient's pediatric quality of life inventory (PedsQL) of 37/30/31 points; parental PedsQL of 26/27/34 points; and patient's pain visual-analog scale (VAS) of 75/45/40, with no VAS recorded for the mother. Juvenile arthritis functional assessment report (JAFAR) scores of 35/34/8 points were observed. A significant reduction in the taking of NSAIDs was observed. In the second half of the year, the nasal breathing became normal, and remission in chronic rhinitis and adenoiditis was achieved (no infection episodes) without otitis episodes. Etanercept in mucopolysaccharidosis type 1 is safe and well tolerated. The reduction of joint pain and increased walking capacity were observed. A decreased number of respiratory infection episodes and nasal breathing improvement were noted during the treatment. The observation shows the role of inflammation in the different aspects of MPS. Further investigations on immune system dysregulation in patients with MPS I are needed. Additional studies on the efficacy and safety of anti-rheumatic biological drugs in patients with MPSI are required.