Epidemiology of Sanfilippo syndrome: results of a systematic literature review

Abstract

BackgroundSanfilippo syndrome (mucopolysaccharidosis [MPS] III subtypes A, B, C, and D) is a rare autosomal recessive inherited metabolic disorder that causes progressive neurocognitive degeneration. This systematic literature review was undertaken to compile and assess published epidemiological data, including various frequency measures and geographical variation on Sanfilippo syndrome.MethodsThe following databases were systematically searched for terms related to Sanfilippo syndrome epidemiology: Medline, Embase, Cochrane Database of Systematic Reviews, Academic Search Complete, Cumulative Index to Nursing and Allied Health Literature, and the Centre for Reviews and Dissemination. Qualitative synthesis of research findings was performed.ResultsOf 2794 publications found in the initial search, 116 were deemed eligible after title and abstract screening. Following full-text review, 46 papers were included in the qualitative synthesis. Results of this systematic literature review indicate that lifetime risk at birth ranges from 0.17–2.35 per 100,000 live births for all 4 subtypes of MPS III together, and from 0.00–1.62 per 100,000 live births for the most frequent subtype, MPS IIIA.ConclusionAll 4 subtypes of MPS III are exceptionally rare, but they each have devastating effects on children. Higher-quality epidemiological data are needed to appropriately target resources for disease research and management.Electronic supplementary materialThe online version of this article (10.1186/s13023-018-0796-4) contains supplementary material, which is available to authorized users.

Assessment of predicted enzymatic activity of α‐ N ‐acetylglucosaminidase variants of unknown significance for CAGI 2016

“…The accumulation of heparan sulfate due to partial or complete loss of NAGLU enzyme activity occurs in various tissues and cells; however, the clinical signs are mostly associated with the central nervous system (Birrane et al, 2019), causing severe cognitive disabilities, behavioral problems and developmental regression, leading to death in adolescence or early adulthood. The age of onset of Sanfilippo Type B is 1-4 years (Andrade, Aldámiz-Echevarría, Llarena, & Couce, 2015) and the estimate for lifetime risk at birth (number of patients per 100,000 live births) varies substantially in European populations from 0.05 in Sweden to 0.78 in Greece (Zelei, Csetneki, Vokó, & Siffel, 2018). To date, no effective treatment for Sanfilippo syndrome exists although several promising approaches are being developed, including enzyme replacement therapy, gene therapy, bone marrow stem cell transplantation and small molecules (Aoyagi-Scharber et al, 2017;Gaffke, Pierzynowska, Piotrowska, & Węgrzyn, 2018).…”

Sanfilippo Syndrome: Molecular Basis, Disease Models and Therapeutic Approaches

“…However, this incidence may underestimate the actual prevalence of different MPS III types because of the difficulties in the correct diagnosis of mild forms. Prevalence of the different subtypes vary between populations; subtype A being more frequent in the Northern Europe and subtype B more frequent in Southern Europe [ 16 ]. On the other hand, subtype C is in general less common while subtype D is very rare in all populations.…”

Psychiatric Symptoms Associated with Inborn Errors of Metabolism

“…The mucopolysaccharidoses are chronic disorders which present after infancy as either severe bone dysplasia or dysmorphic features with learning difficulties, behavior problems, and eventual cognitive decline. They are occasionally associated with other psychiatric symptoms, including sleep and behavior problems, autistic symptoms, and hyperactivity [78,80]. Psychosis occurs with adult onset forms in a variety of mucopolysaccharidoses [].…”

“…This disorder primarily affects the nervous system, and presents early with developmental and speech delay, progressing to severe disruptive behavior, hyperactivity, and profound sleep problems by 3 to 4 years. After age 10, neurologic and psychiatric problems develop, with hyperactivity, chaotic behavior, aggression, restlessness, biting/mouthing, autistic behaviors, and hypersensitivity [80]. Loss of skills continues with slow deterioration into a vegetative state, usually leading to death in the third decade [82].…”