Natural History of Sanfilippo Syndrome Type C in Boyacá, Colombia

Abstract

Mucopolysaccharidosis type III, or Sanfilippo syndrome, is an autosomal recessive disorder characterized by impairment in the degradation of Heparan sulfate. Here the authors describe the natural history of 5 related individuals; all associated through a large pedigree which reports a total of 11 affected members, originally from the Boyacá region in Colombia, diagnosed with MPS IIIC who all harbor a novel mutation in HGSNAT. The authors report an unusually high incidence of the disease in this population. The clinical features are similar to previously described patients, although some differences in the degree of severity and end-stage of the disease are seen in this specific group. The authors consider that the high degree of endogamy in this specific population could underlie modifying factors for the severity of presentation in these patients. Future studies might provide more information on the functional effect of this novel mutation, which could define this group as a genetic isolate.

Mucopolysaccharidosis III in Taiwan: Natural history, clinical and molecular characteristics of 28 patients diagnosed during a 21‐year period

“…Accurate knowledge of the natural course of the disease will help assess disease progression and therapeutic effects, as well as evaluate clinical and biomarker endpoints for clinical trials. The natural course and clinical manifestations of this disorder have been reported by several study groups in Caucasian populations (Buhrman et al, ; Delgadillo et al, ; Héron et al, ; Jansen et al, ; Malm & Månsson, ; Meyer et al, ; Ruijter et al, ; Truxal et al, ; Valstar et al, ; Velasco et al, ). Our results indicate that Taiwanese patients with MPS III manifest a broad spectrum of disease phenotypes from mild to severe, indicating the clinical heterogeneity of the disease.…”

“…There are several reports describing the natural course of MPS III in Caucasian populations (Buhrman, Thakkar, Poe, & Escolar, ; Delgadillo, O'Callaghan, Gort, Coll, & Pineda, ; Héron et al, ; Jansen et al, ; Malm & Månsson, ; Meyer et al, ; Ruijter et al, ; Truxal et al, ; Valstar et al, ; Velasco, Sanchez, Martin, & Umaña, ). However, information regarding the natural history of this disorder in Asian patients is limited.…”

Molecular characterization of a large group of Mucopolysaccharidosis type IIIC patients reveals the evolutionary history of the disease

“…The frequency and worldwide distribution of the HGSNAT mutations in 25 new MPSIIIC index patients together with those previously reported (Ali Pervaiz et al, ; Canals et al, ; Coutinho et al, ; Fan et al, , ; Fedele & Hopwood, ; Feldhammer, Durand, Mrazova, et al, ; Hrebicek et al, ; Hu et al, ; Huh et al, ; Matos et al, ; Ouesleti et al, , ; Ruijter et al, ; Velasco et al, ) are summarized in Figure . The data show that Europe, South America, and Western Asia are so far the regions with the highest number of families reported with molecular diagnosis of MPSIIIC.…”

“…Mutations in the HGSNAT gene have been identified in MPSIIIC patients from several countries in Europe (Belarus, Belgium, Czech Republic, Finland, Germany, Greece, Ireland, Italy, Poland, Portugal, Spain, the Netherlands, and the UK), North Africa (Morocco and Tunisia), Asia (Turkey, Pakistan, Singapore, and South Korea), North (Canada and USA; Ali Pervaiz et al, ; Canals et al, ; Coutinho et al, ; Fan et al, ; Fan, Tkachyova, Sinha, Rigat, & Mahuran, ; Fedele & Hopwood, ; Fedele et al, ; Feldhammer, Durand, Mrazova, et al, ; Hrebicek et al, ; Hu et al, ; Huh et al, ; Matos et al, ; Ouesleti et al, , ; Ruijter et al, ) and South America (Argentina and Colombia; Canals et al, ; Velasco et al, ). Approximately 30% of all MPSIIIC variants are shared between different populations suggesting the existence of a common ancestor.…”

“…Approximately 30% of all MPSIIIC variants are shared between different populations suggesting the existence of a common ancestor. Besides, certain mutations are present at a relatively high frequency in some geographic regions of Italy, Portugal, the Netherlands, and Colombia possibly due to founder effects (Coutinho et al, ; Fedele et al, ; Ruijter et al, ; Velasco et al, ).…”