Scoring Evaluation of the Natural Course of Mucopolysaccharidosis Type IIIA (Sanfilippo Syndrome Type A)

Meyer, Ann; Kossow, Kai; Gal, Andreas; Mühlhausen, Chris; Ullrich, Kurt; Braulke, Thomas; Muschol, Nicole

doi:10.1542/peds.2007-0282

Cited by 108 publications

(152 citation statements)

References 25 publications

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“…Clinically, the new MPS IIID patients described here seem to follow the general pattern of Sanfilippo syndrome types A, B and C as previously described (Meyer et al, 2007;Ruijter et al, 2008;Valstar et al, 2008;van de Kamp et al, 1981). Development during the first year of life is normal, after which behavioral problems and a progressive mental retardation leading to severe dementia become apparent.…”

Section: Discussionsupporting

confidence: 79%

Mucopolysaccharidosis type IIID: 12 new patients and 15 novel mutations

et al. 2010

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Mucopolysaccharidosis III D (Sanfilippo disease type D, MPS IIID) is a rare autosomal recessive lysosomal storage disorder previously described in only 20 patients. MPS IIID is caused by a deficiency of N-acetylglucosamine-6-sulphate sulphatase (GNS), one of the enzymes required for the degradation of heparan sulphate. So far only seven mutations in the GNS gene have been reported. The clinical phenotype of 12 new MPS IIID patients from 10 families was studied. Mutation analysis of GNS was performed in 16 patients (14 index cases). Clinical signs and symptoms of the MPS IIID patients appeared to be similar to previously described patients with MPS III. Early development was normal with onset of behavioral problems around the age of 4 years, followed by developmental stagnation, deterioration of verbal communication and subsequent deterioration of motor functions. Sequence analysis of the coding regions of the gene encoding GNS (GNS) resulted in the identification of 15 novel mutations: 3 missense mutations, 1 nonsense mutation, 4 splice site mutations, 3 frame shift mutations, 3 large deletions and 1 inframe small deletion. They include the first missense mutations and a relatively high proportion of large rearrangements, which warrants the inclusion of quantitative techniques in routine mutation screening of the GNS gene.

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Section: Discussionsupporting

confidence: 79%

Mucopolysaccharidosis type IIID: 12 new patients and 15 novel mutations

et al. 2010

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“…Lifespan usually does not extend past the second decade. The symptoms correspond with degeneration of the cerebral cortex and other brain regions [4–6] as well as neuroinflammation [4,7]. The underlying cause of MPS IIIB, the subtype analyzed in the present work, is a deficiency of NAGLU/α- N -acetylglucosaminidase, an enzyme that participates in the degradation of heparan sulfate.…”

Section: Introductionmentioning

confidence: 96%

Trehalose reduces retinal degeneration, neuroinflammation and storage burden caused by a lysosomal hydrolase deficiency

et al. 2018

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The accumulation of undegraded molecular material leads to progressive neurodegeneration in a number of lysosomal storage disorders (LSDs) that are caused by functional deficiencies of lysosomal hydrolases. To determine whether inducing macroautophagy/autophagy via small-molecule therapy would be effective for neuropathic LSDs due to enzyme deficiency, we treated a mouse model of mucopolysaccharidosis IIIB (MPS IIIB), a storage disorder caused by deficiency of the enzyme NAGLU (alpha-N-acetylglucosaminidase [Sanfilippo disease IIIB]), with the autophagy-inducing compound trehalose. Treated naglu–/ – mice lived longer, displayed less hyperactivity and anxiety, retained their vision (and retinal photoreceptors), and showed reduced inflammation in the brain and retina. Treated mice also showed improved clearance of autophagic vacuoles in neuronal and glial cells, accompanied by activation of the TFEB transcriptional network that controls lysosomal biogenesis and autophagic flux. Therefore, small-molecule-induced autophagy enhancement can improve the neurological symptoms associated with a lysosomal enzyme deficiency and could provide a viable therapeutic approach to neuropathic LSDs.Abbreviations: ANOVA: analysis of variance; Atg7: autophagy related 7; AV: autophagic vacuoles; CD68: cd68 antigen; ERG: electroretinogram; ERT: enzyme replacement therapy; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GFAP: glial fibrillary acidic protein; GNAT2: guanine nucleotide binding protein, alpha transducing 2; HSCT: hematopoietic stem cell transplantation; INL: inner nuclear layer; LC3: microtubule-associated protein 1 light chain 3 alpha; MPS: mucopolysaccharidoses; NAGLU: alpha-N-acetylglucosaminidase (Sanfilippo disease IIIB); ONL: outer nuclear layer; PBS: phosphate-buffered saline; PRKCA/PKCα: protein kinase C, alpha; S1BF: somatosensory cortex; SQSTM1: sequestosome 1; TEM: transmission electron microscopy; TFEB: transcription factor EB; VMP/VPL: ventral posterior nuclei of the thalamus

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“…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.…”

Section: Discussionmentioning

confidence: 98%