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Mucopolysaccharide diseases (MPS) are caused by deficiency of glycosaminoglycan (GAG) degrading enzymes, leading to GAG accumulation. Neurodegenerative MPS diseases exhibit cognitive decline, behavioural problems and shortened lifespan. We have characterised neuropathological changes in mouse models of MPSI, IIIA and IIIB to provide a better understanding(More)
Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is an X-linked, recessive, lysosomal storage disorder caused by deficiency of iduronate-2-sulfatase. It has multisystemic involvement, with manifestations in the brain, upper respiratory tract, heart, abdomen, joints and bones. Bone involvement leads to decreased growth velocity and short stature in(More)
BACKGROUND Niemann-Pick type C disease (NPC) is an inherited neurodegenerative disorder characterised by an intracellular lipid-trafficking defect with secondary accumulation of glycosphingolipids. Miglustat, a small iminosugar, reversibly inhibits glucosylceramide synthase, which catalyses the first committed step of glycosphingolipid synthesis. Miglustat(More)
BACKGROUND Neurodegenerative metabolic disorders such as mucopolysaccharidosis IIIB (MPSIIIB or Sanfilippo disease) accumulate undegraded substrates in the brain and are often unresponsive to enzyme replacement treatments due to the impermeability of the blood brain barrier to enzyme. MPSIIIB is characterised by behavioural difficulties, cognitive and later(More)
Abnormalities of magnetic resonance imaging (MRI) of the brain occur in some patients with phenylketonuria but the clinical importance of this finding is not clear. In order to determine the frequency and functional significance of changes on MRI we investigated 77 adolescent and adult patients with phenylketonuria. Patients aged 14-49 years and taking a(More)
OBJECTIVE The Suspicion Index (SI) screening tool was developed to identify patients suspected of having Niemann-Pick disease type C (NP-C). The SI provides a risk prediction score (RPS) based on NP-C manifestations within and across domains (visceral, neurological, and psychiatric). The aim of these subanalyses was to further examine the discriminatory(More)
Niemann-Pick disease type C is a rare, genetic disease associated with impaired intracellular lipid trafficking and progressive neurological symptoms. Miglustat slowed disease progression in a 12-month randomized trial in juveniles and adults with Niemann-Pick disease type C, and in a parallel, noncontrolled study in affected children. Here, the authors(More)
Mucopolysaccharidosis IIIB (MPSIIIB) is a lysosomal storage disease characterised by progressive central nervous system degeneration in patients, with death usually in the late teens. Serious behavioural problems have been reported in children at the early stages of the disease, such as hyperactivity and severe sleep disturbances, which suggest alterations(More)
Spiral analysis is a computerized method of analyzing upper limb motor physiology through the quantification of spiral drawing. The objective of this study was to determine whether spirals drawn by patients with Niemann-Pick disease type C (NPC) could be distinguished from those of controls, and to physiologically characterize movement abnormalities in NPC.(More)
Early detection of mucopolysaccharidosis (MPS) is an important factor in treatment success; therefore, good disease biomarkers are vital. We evaluate heparin cofactor II-thrombin complex (HCII-T) as a biomarker in serum and dried blood spots (DBS) of MPS patients. Serum HCII-T and urine dermatan sulphate:chondroitin sulphate (DS:CS) ratio are also compared(More)