Sanfilippo Syndrome: Optimizing Care with a Multidisciplinary Approach

Abstract

Sanfilippo syndrome, or mucopolysaccharidosis type III (MPS III), is a disease grouping five genetic disorders, four of them occurring in humans and one known to date only in a mouse model. In every subtype of MPS III (designed A, B, C, D or E), a lack or drastically decreased activity of an enzyme involved in the degradation of heparan sulfate (HS) (a compound from the group of glycosaminoglycans (GAGs)) arises from a genetic defect. This leads to primary accumulation of HS, and secondary storage of other compounds, combined with changes in expressions of hundreds of genes and many defects in organelles and various biochemical processes in the cell. As a result, dysfunctions of tissues and organs occur, leading to severe symptoms in patients. Although changes in somatic organs are considerable, the central nervous system is especially severely affected, and neurological, cognitive and behavioral disorders are the most significant changes, making the disease enormously burdensome for patients and their families. In the light of the current lack of any registered therapy for Sanfilippo syndrome (despite various attempts of many research groups to develop effective treatment, still no specific drug or procedure is available for MPS III), optimizing care with a multidisciplinary approach is crucial for managing this disease and making quality of patients' life passable. This includes efforts to make/organize (i) accurate diagnosis as early as possible (which is not easy due to various possible misdiagnosis events caused by similarity of MPS III symptoms to those of other diseases and variability of patients), (ii) optimized symptomatic treatment (which is challenging because of complexity of symptoms and often untypical responses of MPS III patients to various drugs), and (iii) psychological care (for both patients and family members and/or caregivers). In this review article, we focus on these approaches, summarizing and discussing them.

Activities of (Poly)phenolic Antioxidants and Other Natural Autophagy Modulators in the Treatment of Sanfilippo Disease: Remarkable Efficacy of Resveratrol in Cellular and Animal Models

“…However, the results of other recent studies performed with a mouse model of MPS IIIA indicated that autistic-like behavior is caused by the increased proliferation of mesencephalic dopamine neurons not lysosomal dysfunction [72]. Notably, these outcomes are characteristic of children suffering from Sanfilippo disease [5,73,74]; hence, the mechanisms underlying to storage disorders are likely to be similar (or the same) in mice and humans. Detailed experiments with a mouse MPS IIIA model suggested that pathological modulation of dopamine activity can be a result of altered HS function, not elevated GAG levels [72].…”

Roles of the Oxytocin Receptor (OXTR) in Human Diseases

“…Such symptoms resemble those described in the preceding section ( Section 4 ) as characteristic of disorders associated with OXTR changes. Indeed, the symptoms of some MPS types, especially all subtypes of MPS III (Sanfilippo disease) are so similar to autism spectrum disorder or attention deficit hyperactivity disorder that MPS III is often misdiagnosed as one of these diseases [ 130 , 131 , 132 , 133 ].…”

Transcriptomic Approaches in Studies on and Applications of Chimeric Antigen Receptor T Cells

“… Schematic representation of the various possibilities of applications of transcriptomic methods in studies on and practical use of CAR-T cells, reported to date in the literature, as depicted in the form of the Cyske rosette chart (a kind of the schematic summary as proposed by Cyske et al [ 85 ]). …”