Incidence and natural history of mucopolysaccharidosis type III in France and comparison with United Kingdom and Greece

Abstract

Sanfilippo syndrome, or mucopolysaccharidosis type III (MPSIII) is a lysosomal storage disease with predominant neurological manifestations in affected children. It is considered heterogeneous with respect to prevalence, clinical presentation, biochemistry (four biochemical forms of the disease referred to as MPSIIIA, B, C, and D are known), and causative mutations. The perspective of therapeutic options emphasizes the need for better knowledge of MPSIII incidence and natural history. We performed parallel retrospective epidemiological studies of patients diagnosed with MSPIII in France (n = 128), UK (n = 126), and Greece (n = 20) from 1990 to 2006. Incidences ranged from 0.68 per 100,000 live-births in France to 1.21 per 100,000 live-births in UK. MPSIIIA, which predominates in France and UK, was absent in Greece, where most patients have MPSIIIB. The study confirmed the large allelic heterogeneity of MPSIIIA and MPSIIIB and detected several yet undescribed mutations. Analysis of clinical manifestations at diagnosis and over a 6-7 years follow-up indicated that almost all patients, whatever the disease subtype, expressed neurological manifestations before the age of 5 years, including language acquisition delay, cognitive delay, and/or abnormal behavior. In contrast to relatively homogeneous early onset manifestations, disease progression showed significant variation depending on subtype and age at diagnosis. Different severities of disease progressions and different allele distribution between France and UK suggested that mutations are not equally deleterious, although genotype-phenotype correlation could not be established. Notwithstanding the rapidity of further clinical deterioration, all MPSIII patients suffer early onset devastating neurological manifestations that deserve early treatment when available.

Chronic idiopathic thrombocytopenic purpura in a child with Sanfilippo type A

“…Among all types of mucopolysaccharidoses, Sanfilippo disease (MPS type III) is the most common entity. 1 Speech delay was the most frequent clinical symptom before diagnosis [2][3][4] and coarse facial features were present before diagnosis in 78% of MPS III patients. 5 Unlike Hurler syndrome (MPS I) or Hunter syndrome (MPS II), patients with Sanfilippo disease often have early very mild coarse facial features.…”

Methods of Neurodevelopmental Assessment in Children with Neurodegenerative Disease: Sanfilippo Syndrome

“…Abnormal behaviors have been described as aggressive and hyperactive with sleep disturbance (Cleary and Wraith 1993;Valstar et al 2011;Meyer et al 2007;Fraser et al 2002). Autistic-like symptoms and loss of normal fear have also been described (Heron et al 2011). In a recent study, (Heron et al 2011) found the average lifespan for MPS IIIA to be 15.4 years (Heron et al 2011).…”

Epilepsy in Children With Mucopolysaccharidosis: Epidemiology, Clinical and Electroencephalographic Features

“…В работах зарубежных [14,15,17], а также российских авторов показано [6,16], что самая высокая доля больных с эпилепсией наблюдается при нейроно-патических типах МПС II и III. По данным международных и отечественных исследователей, среди больных МПС II распространенность эпилепсии колеблется в диапазоне от 13 до 34% [17][18][19], с более высоким процентом (от 28 до 63%) у больных с нейронопатическим феноти-пом [20][21][22]; средний возраст появления эпилептиче-ских приступов -~10 лет [16][17][18]. По данным I.…”