Sanfilippo syndrome type C: A clinicopathological autopsy study of a long-term survivor

Kurihara, Mana; Kumagai, Ken; Yagishita, Saburo

doi:10.1016/0887-8994(96)00083-5

Cited by 25 publications

(23 citation statements)

References 7 publications

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“…1,3 While detailed mechanisms of pathology, especially the neuropathology of MPS III, are not yet well understood, numerous studies have reported cascades of complex secondary pathological events in the CNS, including broad metabolic impairments, [4][5][6] neuroinflammation, 5,7-11 oxidative stress, 10,12 autophagy, 13,14 and neurodegeneration. 7,9,11,[15][16][17][18][19][20] It is worth noting that many of these secondary neuropathological features of MPS IIIB, such as b-amyloid (Ab) aggregation, 15,18 tauopathy, 17,18 synucleinopathy, 16,19 oxidative stress, 10,12 and neuroimflammation, 5,[7][8][9][10][11] are also common hallmarks of other neurodegenerative diseases like Alzheimer's (AD) 21,22 and Parkinson's disease (PD). 23,24 In addition, our recent studies demonstrate widespread profound neuropathology in the peripheral nervous system (PNS), 25 indicating that neuropathological manifestation affects the entire nervous system.…”

Section: Mucopolysaccharidosis (Mps) Iiib (Online Mendelian Inheritanmentioning

confidence: 99%

Near-Complete Correction of Profound Metabolomic Impairments Corresponding to Functional Benefit in MPS IIIB Mice after IV rAAV9-hNAGLU Gene Delivery

Meadows

Ware

et al. 2017

Molecular Therapy

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Mucopolysaccharidosis (MPS) IIIB is a lysosomal storage disease with complex CNS and somatic pathology due to a deficiency in a-N-acetylglucosaminidase (NAGLU). Using global metabolic profiling by mass spectrometry targeting 361 metabolites, this study detected significant decreases in 225 and increases in six metabolites in serum samples from 7-monthold MPS IIIB mice, compared to wild-type (WT) mice. The metabolic disturbances involve virtually all major pathways of amino acid, peptide (58/102), carbohydrate (18/28), lipid (111/139), nucleotide (12/24), energy (2/9), vitamin and cofactor (11/16), and xenobiotic (11/28) metabolism. Notably, the reduced metabolites included eight essential amino acids, vitamins (C, E, B2, and B6), and neurotransmitters (serotonin, glutamate, aspartate, tryptophan, and N-acetyltyrosine). The metabolic impairments appear to emerge early during disease progression before the age of 2 months. Importantly, the restoration of NAGLU activity with an intravenous (i.v.) injection of rAAV9-hNAGLU vector led to near-complete correction of all serum metabolite abnormalities, with 201 (87%) metabolites normalized and 30 (13%) over-corrected. While the mechanisms are unclear, our data demonstrate that the lack of NAGLU activity triggers profound functional metabolic disturbances in MPS IIIB. These metabolic impairments respond well to a systemic rAAV9-hNAGLU gene delivery, supporting the surrogate biomarker potential of serum metabolomic profiles for MPS IIIB therapies.

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Section: Mucopolysaccharidosis (Mps) Iiib (Online Mendelian Inheritanmentioning

confidence: 99%

Near-Complete Correction of Profound Metabolomic Impairments Corresponding to Functional Benefit in MPS IIIB Mice after IV rAAV9-hNAGLU Gene Delivery

Meadows

Ware

et al. 2017

Molecular Therapy

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“…Secondary to the lysosomal pathology in neurons and glial cells, the brains of MPS IIIA mice are characterized by the presence of extensive neuroinflammation (8,20), a common feature of MPS III in humans (34,35). To evaluate the effect of AAV9-Sgsh gene transfer on brain inflammation, MPS IIIA mice injected with AAV9-Sgsh or AAV9-null vector were analyzed in parallel to WT mice 4 months after vector delivery.…”

Section: Figurementioning

confidence: 99%

Whole body correction of mucopolysaccharidosis IIIA by intracerebrospinal fluid gene therapy

Haurigot¹,

Matarazzo²,

Ribera³

et al. 2013

J. Clin. Invest.

189

246

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“…A 6-year-old girl with Sanfilippo syndrome, type B was diagnosed with severe mitral regurgitation and consequently underwent mitral valve repair (9). Further, the autopsy of 39 year-old woman with Sanfilippo syndrome, type C, who died of acute cardiac failure, revealed focal myocardial necrosis replaced by vacuolated cells and fibrosis (10). The present patient may be the first patient with Sanfilippo syndrome, type C to have developed an atrioventricular block.…”

Section: Discussionmentioning

confidence: 91%

Atrioventricular Block and Diastolic Dysfunction in a Patient with Sanfilippo C

Misumi¹,

Chikazawa²,

Ishitsu³

et al. 2010

Intern. Med.

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A 39-year-old woman with Sanfilippo C syndrome was referred to our department for the treatment of bradycardia. An electrocardiogram revealed a second degree atrioventricular block, and pacemaker implantation was performed with the patient under general anesthesia. A transthoracic echocardiogram showed normal left ventricular systolic function, moderate mitral regurgitation due to mitral valve prolapse, and a high E/e' ratio, indicating left ventricular diastolic dysfunction. The present patient exhibited a rare case of Sanfilippo syndrome complicated with conduction disturbances, mitral regurgitation, and diastolic dysfunction.

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Sanfilippo syndrome type C: A clinicopathological autopsy study of a long-term survivor

Cited by 25 publications

References 7 publications

Near-Complete Correction of Profound Metabolomic Impairments Corresponding to Functional Benefit in MPS IIIB Mice after IV rAAV9-hNAGLU Gene Delivery

Near-Complete Correction of Profound Metabolomic Impairments Corresponding to Functional Benefit in MPS IIIB Mice after IV rAAV9-hNAGLU Gene Delivery

Whole body correction of mucopolysaccharidosis IIIA by intracerebrospinal fluid gene therapy

Atrioventricular Block and Diastolic Dysfunction in a Patient with Sanfilippo C

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