No 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.

Aims The mucopolysaccharidoses (MPS) are a heterogeneous group of rare disorders characterised by accumulation of glycosaminoglycans within multiple organ systems. This study aimed to determine the prevalence and severity of ocular complications in patients with MPS. Methods Clinical ophthalmic features and electrodiagnostic results of 50 patients with a diagnosis of MPS were retrospectively reviewed. Results A total of 79% of MPS IH patients had a visual acuity of less than 6/12 equivalent in their better eye, compared to 44% of MPS IH/S and 25% of MPS VI patients. In total, 16% of MPS IH and 25% of MPS IH/S had severe corneal opacification, compared to 38% of MPS VI patients. 16% of MPS IH patients had optic atrophy; 21% of MPS VI patients had mild disc swelling, 29% had markedly swollen discs, and 14% had optic atrophy. One patient with MPS IH, one with MPS IH/S and six with MPS VI had ocular hypertension. One MPS VI patient had glaucoma that required topical therapy. Nine patients with MPS IH had electrodiagnostic evidence of retinopathy, as did one MPS VI patient. Conclusions Ocular complications causing significant reduction in vision are common in MPS. The majority of MPS I and MPS VI patients have corneal opacification, which can lead to difficulties in diagnosis and monitoring of glaucoma, optic disc changes, and retinopathy.

Hunter syndrome is a rare, X-linked disorder caused by a deficiency of the lysosomal enzyme iduronate-2-sulfatase. In the absence of sufficient enzyme activity, glycosaminoglycans accumulate in the lysosomes of many tissues and organs and contribute to the multisystem, progressive pathologies seen in Hunter syndrome. The nervous, cardiovascular, respiratory, and musculoskeletal systems can be involved in individuals with Hunter syndrome. Although the management of some clinical problems associated with the disease may seem routine, the management is typically complex and requires the physician to be aware of the special issues surrounding the patient with Hunter syndrome, and a multidisciplinary approach should be taken. Subspecialties such as otorhinolaryngology, neurosurgery, orthopedics, cardiology, anesthesiology, pulmonology, and neurodevelopment will all have a role in management, as will specialty areas such as physiotherapy, audiology, and others. The important management topics are discussed in this review, and the use of enzyme-replacement therapy with recombinant human iduronate-2-sulfatase as a specific treatment for Hunter syndrome is presented.

• In HS, patients' early referral for HCT, with the best available HLA-matched donor offers the best event-free survival.• In HS, patients' HCT with a well-matched unrelated cord blood unit is particularly attractive because the unit is readily available.We report transplantation outcomes of 258 children with Hurler syndrome (HS) after a myeloablative conditioning regimen from 1995 to 2007. Median age at transplant was 16.7 months and median follow-up was 57 months. The cumulative incidence of neutrophil recovery at day 60 was 91%, acute graft-versus-host disease (GVHD) (grade II-IV) at day 100 was 25%, and chronic GVHD and 5 years was 16%. Overall survival and event-free survival (EFS) at 5 years were 74% and 63%, respectively. EFS after HLA-matched sibling donor (MSD) and 6/6 matched unrelated cord blood (CB) donor were similar at 81%, 66% after 10/10 HLA-matched unrelated donor (UD), and 68% after 5/6 matched CB donor. EFS was lower after transplantation in 4/6 matched unrelated CB (UCB) (57%; P 5 .031) and HLA-mismatched UD (41%; P 5 .007). Full-donor chimerism (P 5 .039) and normal enzyme levels (P 5 .007) were higher after CB transplantation (92% and 98%, respectively) compared with the other grafts sources (69% and 59%, respectively). In conclusion, results of allogeneic transplantation for HS are encouraging, with similar EFS rates after MSD, 6/6 matched UCB, 5/6 UCB, and 10/10 matched UD. The use of mismatched UD and 4/6 matched UCB was associated with lower EFS. (Blood. 2013;121(19):3981-3987)