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.

Sanfilippo disease (mucopolysaccharidosis, MPS IIIA) is one of the types of mucopolysaccharidosis associated with extensive neurological effects and somatic symptoms. The consequences of neurodegeneration and cognitive impairment are manifested in challenges with the daily functioning of patients who experience problems with communication and following instructions. The aim of this study was to assess the cognitive functioning of three patients with MPS IIIA and to find patterns of neurodegeneration and to make their environment more friendly. Three boys (from 5.5 to 7 years) with MPS IIIA participated in the study. Each participant attended two meetings, and his functioning was assessed by three independent person (using two-way mirror). We used Bayley’s Scale III with some modifications. Interviews with parents were also included. The communication of patients was limited to some vocalizations. Patients presented instrumental use of items, but not all of them were able to repeat actions after diagnostician or presented object permanence. The results showed that the cognitive functioning of participants was significantly hindered by problems related to motor dysfunction, hyperactivity, and ataxia. The psychological data was collated with medical results. This study allows indicating new sources giving the possibility of child phenotype variability and to create specific interventions in the field of psychological therapy for patients with MPS IIIA and their families.

Background Sanfilippo syndrome B (or mucopolysaccharidosis type IIIB [MPS IIIB]) is a severe inherited metabolic disorder caused by mutations in the NAGLU gene, encoding α‐N‐acetylglucosaminidase. Dysfunction of this enzyme results in impaired degradation of heparan sulfate, one of glycosaminoglycans, and accumulation of this complex carbohydrate in lysosomes. Severe symptoms occurring in this disease are related to progressive neurodegeneration and include extreme hyperactivity, sleeping problems, aggressive‐like behavior, reduced fear, and progressive mental and cognitive deterioration. No cure is currently available for Sanfilippo disease. Methods Clinical characterization of the patient's symptoms has been performed. Biochemical analyses included glycosaminoglycan level determination and measurement of α‐N‐acetylglucosaminidase activity. Molecular analyses included exome sequencing and detailed analysis of the NAGLU gene. Psychological tests included assessment of attention, communication and behavior. Results We describe a patient with an untypically mild phenotype, who was diagnosed at the age of 13 years. Many cognitive, communication, and motoric functions were preserved in this patient, contrary to vast majority of those suffering from MPS IIIB. The patient is a compound heterozygote (c.638C>T/c.889C>T) in the NAGLU gene, and relatively high residual activity (about 25%) of α‐N‐acetylglucosaminidase was measured in serum (while no activity of this enzyme could be detected in dry blood spot). Conclusions We suggest that the mild phenotype might arise from the partially preserved function of the mutant enzyme (p.Pro213Leu), suggesting the genotype‐phenotype correlation in this case.

Background: The relationship between intelligence quotient (IQ) and somatic development, especially growth, has been demonstrated in various groups of children. Down syndrome (DS) is characterized by short stature, overweight, and cognitive impairment. The objective of our work was to assess whether anthropometric measurements [weight, height, body mass index (BMI)] of children with DS correlate with their IQ. The results of the study may be valuable for this population in the light of increasing access to growth hormone therapy (GHT) in various genetic syndromes with short stature. Based on previous studies on children, we hypothesized that a link exists between IQ and somatic development, particularly growth.Methods: This cross-sectional study included 40 children with DS, who were aged 9-18 years. The studied population was selected from the registry of the Genetic Clinic at the University Clinical Center in Gdańsk (Poland). Anthropometric measurements (weight and height) were taken for all the children, and their BMI was determined using these data. The obtained results were plotted on charts for children with DS. The IQ of the children was assessed using the Stanford Binet Intelligence Scale, Fifth Edition. The correlations between IQ and anthropometric data were analyzed using univariate correlation and multiple regression analyses. Results:The results showed that full-scale, verbal, and nonverbal IQ correlated with height percentile (P=0.03, P=0.02, and P=0.04, respectively), but not with weight (P=0. 26, P=0.19, and P=0.61, respectively) or BMI (P=0.6, P=0.5, and P=0.72, respectively). In multiple linear regression analysis, height percentile remained as an independent determinant of the IQ results after adjusting for birth weight, hypothyroidism with L-thyroxine replacement therapy, and congenital cardiac defect (β=0.48, P=0.018). Conclusions:The results of our study suggest an association between growth and IQ in children with DS. The presented findings may be valuable for improving access to GHT for populations with genetic syndromes characterized by short stature. However, these should be confirmed by further research with a longitudinal sample of children with DS.

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