Mucopolysaccharidosis IV: Genetic disorder of mucopolysaccharide metabolism characterized by skeletal abnormalities, joint instability, development of cervical myelopathy, and excessive urinary keratan sulfate. There are two biochemically distinct forms, each due to a deficiency of a different enzyme.Chondroitinsulfatases: A group of enzymes that catalyze the hydrolysis of various sulfate bonds of chondroitin sulfate. EC 3.1.6.-.Mucopolysaccharidosis I: Systemic lysosomal storage disease caused by a deficiency of alpha-L-iduronidase (IDURONIDASE) and characterized by progressive physical deterioration with urinary excretion of DERMATAN SULFATE and HEPARAN SULFATE. There are three recognized phenotypes representing a spectrum of clinical severity from severe to mild: Hurler syndrome, Hurler-Scheie syndrome and Scheie syndrome (formerly mucopolysaccharidosis V). Symptoms may include DWARFISM; hepatosplenomegaly; thick, coarse facial features with low nasal bridge; corneal clouding; cardiac complications; and noisy breathing.Mucopolysaccharidosis VI: Mucopolysaccharidosis with excessive CHONDROITIN SULFATE B in urine, characterized by dwarfism and deafness. It is caused by a deficiency of N-ACETYLGALACTOSAMINE-4-SULFATASE (arylsulfatase B).Mucopolysaccharidosis VII: Mucopolysaccharidosis characterized by excessive dermatan and heparan sulfates in the urine and Hurler-like features. It is caused by a deficiency of beta-glucuronidase.Mucopolysaccharidosis III: Mucopolysaccharidosis characterized by heparitin sulfate in the urine, progressive mental retardation, mild dwarfism, and other skeletal disorders. There are four clinically indistinguishable but biochemically distinct forms, each due to a deficiency of a different enzyme.Mucopolysaccharidosis II: Systemic lysosomal storage disease marked by progressive physical deterioration and caused by a deficiency of L-sulfoiduronate sulfatase. This disease differs from MUCOPOLYSACCHARIDOSIS I by slower progression, lack of corneal clouding, and X-linked rather than autosomal recessive inheritance. The mild form produces near-normal intelligence and life span. The severe form usually causes death by age 15.Mucopolysaccharidoses: Group of lysosomal storage diseases each caused by an inherited deficiency of an enzyme involved in the degradation of glycosaminoglycans (mucopolysaccharides). The diseases are progressive and often display a wide spectrum of clinical severity within one enzyme deficiency.Iduronidase: An enzyme that hydrolyzes iduronosidic linkages in desulfated dermatan. Deficiency of this enzyme produces Hurler's syndrome. EC 3.2.1.76.N-Acetylgalactosamine-4-Sulfatase: An arylsulfatase that catalyzes the hydrolysis of the 4-sulfate groups of the N-acetyl-D-galactosamine 4-sulfate units of chondroitin sulfate and dermatan sulfate. A deficiency of this enzyme is responsible for the inherited lysosomal disease, Maroteaux-Lamy syndrome (MUCOPOLYSACCHARIDOSIS VI). EC 3.1.6.12.Chondro-4-Sulfatase: An enzyme from the sulfuric ester hydrolase class that breaks down one of the products of the chondroitin lyase II reaction. EC 3.1.6.9.Iduronate Sulfatase: An enzyme that specifically cleaves the ester sulfate of iduronic acid. Its deficiency has been demonstrated in Hunter's syndrome, which is characterized by an excess of dermatan sulfate and heparan sulfate. EC 3.1.6.13.Enzyme Replacement Therapy: Therapeutic replacement or supplementation of defective or missing enzymes to alleviate the effects of enzyme deficiency (e.g., GLUCOSYLCERAMIDASE replacement for GAUCHER DISEASE).GlucuronidaseGlycosaminoglycans: Heteropolysaccharides which contain an N-acetylated hexosamine in a characteristic repeating disaccharide unit. The repeating structure of each disaccharide involves alternate 1,4- and 1,3-linkages consisting of either N-acetylglucosamine or N-acetylgalactosamine.SulfatasesLysosomes: A class of morphologically heterogeneous cytoplasmic particles in animal and plant tissues characterized by their content of hydrolytic enzymes and the structure-linked latency of these enzymes. The intracellular functions of lysosomes depend on their lytic potential. The single unit membrane of the lysosome acts as a barrier between the enzymes enclosed in the lysosome and the external substrate. The activity of the enzymes contained in lysosomes is limited or nil unless the vesicle in which they are enclosed is ruptured. Such rupture is supposed to be under metabolic (hormonal) control. (From Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)Acetylglucosaminidase: A beta-N-Acetylhexosaminidase that catalyzes the hydrolysis of terminal, non-reducing 2-acetamido-2-deoxy-beta-glucose residues in chitobiose and higher analogs as well as in glycoproteins. Has been used widely in structural studies on bacterial cell walls and in the study of diseases such as MUCOLIPIDOSIS and various inflammatory disorders of muscle and connective tissue.Stomatognathic System: The mouth, teeth, jaws, pharynx, and related structures as they relate to mastication, deglutition, and speech.Lysosomal Storage Diseases: Inborn errors of metabolism characterized by defects in specific lysosomal hydrolases and resulting in intracellular accumulation of unmetabolized substrates.Enzyme Therapy: The use of enzymes to correct metabolic and physiological processes.Genetic Therapy: Techniques and strategies which include the use of coding sequences and other conventional or radical means to transform or modify cells for the purpose of treating or reversing disease conditions.

*  A Study to Evaluate the Long-Term Efficacy and Safety of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome...

Mucopolysaccharidosis IV type A. MPS IV Type A. Mucopolysaccharidosis IVA. MPS IVA. Morquio A Syndrome. Lysosomal Storage ... Mucopolysaccharidoses. Mucopolysaccharidosis IV. Disease. Pathologic Processes. Carbohydrate Metabolism, Inborn Errors. ... Genetic and Rare Diseases Information Center resources: Mucopolysaccharidosis Mucopolysaccharidosis Type IV ... MPS IV A Mucopolysaccharidosis IVA Morquio A Syndrome Drug: BMN 110 Phase 1 Phase 2 ...
https://clinicaltrials.gov/ct2/show/NCT01242111

*  5 Things You Need to Know From BioMarin's R&D Day -- The Motley Fool

... also known as mucopolysaccharidosis IV type A, or MPS IVA). Biomarin submitted the drug for regulatory approval in the U.S. and ...
https://fool.com/investing/general/2013/09/18/5-things-you-need-to-know-from-biomarins-rd-day.aspx

*  Morquio syndrome | Radiology Reference Article | Radiopaedia.org

... type IV. Epidemiology Incidence estimated at ~1:40,000. Clinical presentation Many cases present at ~2 years of age and have ... Morquio syndrome is an autosomal recessive mucopolysaccharidosis (MPS), ... Morquio syndrome is an autosomal recessive mucopolysaccharidosis (MPS), type IV.. On this page:. ...
https://radiopaedia.org/articles/morquio-syndrome

*  Discovering New Biomarkers For Monitoring Disease Progression in Patients With Mucopolysaccharidosis IVA - Full Text View -...

Mucopolysaccharidosis Type IVA. Mucopolysaccharidosis Type IV. MPS Type IVA. MPS Type IV. Morquio Syndrome. Morquio Syndrome ... Mucopolysaccharidoses. Mucopolysaccharidosis IV. Disease Progression. Disease Attributes. Pathologic Processes. Carbohydrate ... Genetic and Rare Diseases Information Center resources: Mucopolysaccharidosis Mucopolysaccharidosis Type IV ... Discovering New Biomarkers For Monitoring Disease Progression in Patients With Mucopolysaccharidosis IVA. This study has been ...
https://clinicaltrials.gov/ct2/show/NCT01733615?term=Mucopolysaccharidoses&rank=2

*  Keratan Sulfate Quantitative , Urine - Wyoming Medical Center

Mucopolysaccharidosis IV (Morquio syndrome) is caused by defective degradation of keratan sulfate due to deficiency of either N ... The mucopolysaccharidoses (MPS) are a group of disorders caused by the deficiency of any of the enzymes involved in the ... 2. Tomatsu S, Sawamoto K, Shimada T, et al: Enzyme replacement therapy for treating mucopolysaccharidosis type IVA (Morquio A ... 1. Neufeld EF, Muenzer J: The Mucopolysaccharidoses. In The Online metabolic and Molecular Bases of Inherited Disease. Edited ...
wyomingmedicalcenter.testcatalog.org/show/KSQNU

*  List of Mucopolysaccharidosis Type IV Medications (2 Compared) - Drugs.com

Compare risks and benefits of common medications used for Mucopolysaccharidosis Type IV. Find the most popular drugs, view ... What is Mucopolysaccharidosis Type IV: Mucopolysaccharidosis Type IV is a rare, lysosomal storage disease caused by a ... Medications to treat Mucopolysaccharidosis Type IV. The following list of medications are in some way related to, or used in ... Looking for answers? Ask a question or go join the mucopolysaccharidosis type iva support group to connect with others who have ...
https://drugs.com/condition/mucopolysaccharidosis-type-iv.html

*  Google Health - Weaver - Terveysmittari

Mucopolysaccharidosis II. Mucopolysaccharidosis III. Mucopolysaccharidosis IV. Mucopolysaccharidosis I S. Mucormycosis. Multi- ...
helsinki.fi/~pjojala/Google-Health-Weaver-Terveys.htm

*  Diagnosis of Mucopolysaccharidosis Disorders in Patients Presenting With Bilateral Hip Disease - Full Text View -...

Mucopolysaccharidoses. Mucopolysaccharidosis VI. Mucopolysaccharidosis IV. Osteochondrodysplasias. Carbohydrate Metabolism, ... Mucopolysaccharidosis Type IV Mucopolysaccharidosis Type IVA Mucopolysaccharidosis Type VI ... mucopolysaccharidosis type IV mucopolysaccharidosis type VI multiple epiphyseal dysplasia ... Diagnosis of Mucopolysaccharidosis Disorders in Patients Presenting With Bilateral Hip Disease. Resource links provided by NLM: ...
https://clinicaltrials.gov/ct2/show/NCT01707433?term=Mucopolysaccharidoses&rank=6

*  Vimizim Side Effects in Detail - Drugs.com

Mucopolysaccharidosis Type IV. Disclaimer: Every effort has been made to ensure that the information provided is accurate, up- ...
https://drugs.com/sfx/vimizim-side-effects.html

*  rs180869784 - SNPedia

Mucopolysaccharidosis, MPS-IV-B Reversed 0. HGVS NC_000003.11:g.33060002G,A ...
https://snpedia.com/index.php/Rs180869784

*  rs118204436 - SNPedia

Mucopolysaccharidosis, MPS-IV-A Reversed 1. HGVS NC_000016.9:g.88907409A,G ...
https://snpedia.com/index.php/Rs118204436

*  rs398123438 - SNPedia

not provided Mucopolysaccharidosis, MPS-IV-A Reversed 1. HGVS NC_000016.9:g.88904133C,T ...
https://snpedia.com/index.php/Rs398123438

*  rs118204437 - SNPedia

Mucopolysaccharidosis, MPS-IV-A not provided Reversed 1. HGVS NC_000016.9:g.88891261G,A ...
https://snpedia.com/index.php/Rs118204437

*  Lysosomal Storage Disorders: Valentine's Day FDA Approval | Orphan Druganaut Blog

... for the treatment of LSD Mucopolysaccharidosis Type IV A (Morquio A syndrome). The late FDA approval on… ... for the treatment of LSD Mucopolysaccharidosis Type IV A (Morquio A syndrome). The late FDA approval on Valentine's Day, ends ... BioMarin Pharmaceutical, Elosulfase Alfa, Lysosomal Storage Disorders, Morquio A syndrome, Mucopolysaccharidosis, Orphan Drug, ... From → BioMarin Pharmaceutical, Elosulfase Alfa, Lysosomal Storage Disorders, Morquio A syndrome, Mucopolysaccharidosis, Orphan ...
https://orphandruganaut.wordpress.com/2014/02/15/lysosomal-storage-disorders-valentines-day-fda-approval/

*  IHC (Paraffin section) Antibodies - Support (IHC-P): Novus Biologicals

Mucopolysaccharidoses (1). *. Mucopolysaccharidosis Iv (10). *. Multiple Epiphyseal Dysplasia (2). *. Multiple Fractures (6) ...
https://novusbio.com/applications/Immunohistochemistry-Paraffin?related_diseases=Scoliosis, Unspecified

*  FDA Orphan Drug Designations: 2014 9-Month Approval Rate | Orphan Druganaut Blog

Mucopolysaccharidosis (MPS) Type IV A (Morquio A syndrome). 02.14.14. BioMarin Pharmaceutical. ...
https://orphandruganaut.wordpress.com/2014/10/21/fda-orphan-drug-designations-2014-9-month-approval-rate/

*  type species

type iv mucopolysaccharidosis * type locality * type metal * type section * type site * type species ...
dictionary.com/browse/type-species

*  DPPIV/CD26 Assay kit for biological samples - BML-AK498 - Enzo Life Sciences

Monitoring of dipeptidyl peptidase-IV (DPP-IV) activity in patients with mucopolysaccharidoses types I and II on enzyme ... 49, 458 (2016), Application(s): Measured plasma DPP-IV, Abstract;. Effect of dipeptidyl peptidase-4 inhibition on circadian ...
enzolifesciences.com/BML-AK498/dppiv-cd26-assay-kit-for-biological-samples/

*  The Effect of Treatment With Teriparatide and Zoledronic Acid in Patients With Osteogenesis Imperfecta - Full Text View -...

Genetic and Rare Diseases Information Center resources: Osteogenesis Imperfecta Mucopolysaccharidosis Type IV ...
https://clinicaltrials.gov/ct2/show/NCT01679080?recr=Open&cond="Osteogenesis Imperfecta"&rank=7

*  Hunter Syndrome (Mucopolysaccharidosis Type II): Background, Pathophysiology, Epidemiology

... is a member of a group of inherited metabolic disorders collectively termed mucopolysaccharidoses (MPSs). The MPSs are caused ... Brusius-Facchin AC, Abrahão L, Schwartz IV, Lourenço CM, Santos ES, Zanetti A, et al. Extension of the molecular analysis to ... Hunter Syndrome (Mucopolysaccharidosis Type II). Updated: Jul 28, 2015 * Author: Germaine L Defendi, MD, MS, FAAP; Chief Editor ... Mucopolysaccharidosis type II in females and response to enzyme replacement therapy. Am J Med Genet A. 2012 Feb. 158A(2):450-4 ...
https://emedicine.medscape.com/article/944723-overview

*  Medical Genetics Test Services - Baylor Genetics Laboratories - Baylor College of Medicine, Houston, Texas

Mitochondrial Respiratory Chain Complex IV Deficiency (12 nuclear gene panel by NGS) ... Mucopolysaccharidosis Type IIIA (Sanfilippo A). Mucopolysaccharidosis Type IVA. Multiple Acyl-CoA Dehydrogenase Deficiency - ...
https://bcm.edu/research/medical-genetics-labs/tests.cfm?cfid=340488137&cftoken=46268151

*  Case Management Examples - Xian-Lun Zhu, M.D. - The ISPN Guide to Pediatric Neurosurgery

Exposure of the ventricle floor: Seen is the inferior part of the IV ventricle between the tonsils and the vermis. A telovelar ... Radiological Features of Mucopolysaccharidoses. *Radiological Features of Osteogenesis Imperfecta. *Radiological Features of ... Cranial nerve IV was identified and preserved. Because the lesion was highly vascular, circumferential excision was used. ... Postoperatively the patient had partial palsy of cranial nerves II and IV, which resolved in 6 months. Pathological examination ...
https://ispn.guide/vascular-disorders-of-the-nervous-system-in-children/cavernous-malformations-in-children-homepage/management-of-cavernous-malformations-in-children/tips-and-techniques-for-treatment-of-cavernous-malformations-in-children/case-management-examples-xian-lun-zhu-m-d/

*  Behavioral deficits, early gliosis, dysmyelination and synaptic dysfunction in a mouse model of mucolipidosis IV | Acta...

Neuropathology in mouse models of mucopolysaccharidosis type I, IIIA and IIIB. PLoS One 2012, 7(4):e35787. doi:10.1371/journal. ... Mucolipidosis IV Lysosomal storage disease Neuropathology In vivo Ca2+ imaging Glia Introduction. Mucolipidosis IV (MLIV) is a ... 1998) Mucolipidosis type IV: characteristic MRI findings. Neurology 51:565-569 10.1212/WNL.51.2.565View ArticlePubMedGoogle ... A grid size of 175 μm × 175 μm was used for the thalamus, 225 μm × 225 μm was used for laminae IV and V of the S1BF, and 125 μm ...
https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-014-0133-7

*  Your Local Epilepsy Foundation | Epilepsy Foundation

Session IV: Early Stage Devices * SUDEP Challenge / Shark Tank / Lifetime Accelerator Award ...
epilepsy.com/affiliates

*  Dermatology Articles (Diagnosis, Dermatologic Surgery, Histology, Prognosis, Follow-up) - Medscape Reference

Genetics of Mucopolysaccharidosis Type IV. *Genetics of Mucopolysaccharidosis Type VI. *Genetics of Mucopolysaccharidosis Type ...
https://emedicine.medscape.com/dermatology

(1/75) Molecular basis of GM1 gangliosidosis and Morquio disease, type B. Structure-function studies of lysosomal beta-galactosidase and the non-lysosomal beta-galactosidase-like protein.

GM1 gangliosidosis and Morquio B disease are distinct disorders both clinically and biochemically yet they arise from the same beta-galactosidase enzyme deficiency. On the other hand, galactosialidosis and sialidosis share common clinical and biochemical features, yet they arise from two separate enzyme deficiencies, namely, protective protein/cathepsin A and neuraminidase, respectively. However distinct, in practice these disorders overlap both clinically and biochemically so that easy discrimination between them is sometimes difficult. The principle reason for this may be found in the fact that these three enzymes form a unique complex in lysosomes that is required for their stability and posttranslational processing. In this review, I focus mainly on the primary and secondary beta-galactosidase deficiency states and offer some hypotheses to account for differences between GM1 gangliosidosis and Morquio B disease.  (+info)

(2/75) The mouse N-acetylgalactosamine-6-sulfate sulfatase (Galns) gene: cDNA isolation, genomic characterization, chromosomal assignment and analysis of the 5'-flanking region.

Deficiency of lysosomal enzyme N-acetylgalactosamine-6-sulfate sulfatase (GALNS) leads to mucopolysaccharidosis IV A (MPS IV A), for which there is no definitive treatment so far. Although a number of mutations of the GALNS gene of MPS IV A patients have been described, pathogenesis of the disorder still remains elusive. In order to facilitate in vivo studies using model animals for MPS IV A, we isolated and performed molecular characterization of the mouse homolog of human GALNS. The 2.3-kb cDNA contains a 1560-bp open reading frame encoding 520 amino acid residues. The coding region has 84% similarity to the human GALNS cDNA at amino acid level. The mouse Galns gene was mapped by interspecific backcross analysis to the distal region of chromosome 8 where it co-segregates with Aprt. Northern blot analysis showed a wide expression of a single-copy gene, being higher especially in liver and kidney. The Galns gene was isolated from S129vJ genomic library and its genomic organization was characterized. The mouse Galns gene was about 50-kb long and organized into 14 exons and 13 introns. All intron-exon splice junctions conformed to the GT/AG consensus sequence except exon 8/intron 8 junction. Primer extension shows multiple transcription initiation sites between -44 and -75 although major transcription initiation site was observed at -90 bp from the ATG codon. The 5'-flanking region lacks canonical TATA and CAAT box sequences, but is G+C rich with 10 GC boxes (potential Sp1 binding sites), characteristic of a housekeeping gene promoter.  (+info)

(3/75) Biochemical and structural analysis of missense mutations in N-acetylgalactosamine-6-sulfate sulfatase causing mucopolysaccharidosis IVA phenotypes.

Mucopolysaccharidosis IVA (MPS IVA; OMIM#253000), a lysosomal storage disorder caused by a deficiency of N -acetylgalactosamine-6-sulfate sulfatase (GALNS), has variable clinical phenotypes. To date we have identified 65 missense mutations in the GALNS gene from MPS IVA patients, but the correlation between genotype and phenotype has remained unclear. We studied 17 missense mutations using biochemical approaches and 32 missense mutations, using structural analyses. Fifteen missense mutations and two newly engineered active site mutations (C79S, C79T) were characterized by transient expression analysis. Mutant proteins, except for C79S and C79T, were destabilized and detected as insoluble precursor forms while the C79S and C79T mutants were of a soluble mature size. Mutants found in the severe phenotype had no activity. Mutants found in the mild phenotype had a considerable residual activity (1.3-13.3% of wild-type GALNS activity). Sulfatases, including GALNS, are members of a highly conserved gene family sharing an extensive sequence homology. Thus, a tertiary structural model of human GALNS was constructed from the X-ray crystal structure of N -acetylgalacto-samine-4-sulfatase and arylsulfatase A, using homology modeling, and 32 missense mutations were investigated. Consequently, we propose that there are at least three different reasons for the severe phenotype: (i) destruction of the hydrophobic core or modification of the packing; (ii) removal of a salt bridge to destabilize the entire conformation; (iii) modification of the active site. In contrast, mild mutations were mostly located on the surface of the GALNS protein. These studies shed further light on the genotype-phenotype correlation of MPS IVA and structure-function relationship in the sulfatase family.  (+info)

(4/75) Impaired elastic-fiber assembly by fibroblasts from patients with either Morquio B disease or infantile GM1-gangliosidosis is linked to deficiency in the 67-kD spliced variant of beta-galactosidase.

We have previously shown that intracellular trafficking and extracellular assembly of tropoelastin into elastic fibers is facilitated by the 67-kD elastin-binding protein identical to an enzymatically inactive, alternatively spliced variant of beta-galactosidase (S-Gal). In the present study, we investigated elastic-fiber assembly in cultures of dermal fibroblasts from patients with either Morquio B disease or GM1-gangliosidosis who bore different mutations of the beta-galactosidase gene. We found that fibroblasts taken from patients with an adult form of GM1-gangliosidosis and from patients with an infantile form, carrying a missense mutations in the beta-galactosidase gene-mutations that caused deficiency in lysosomal beta-galactosidase but not in S-Gal-assembled normal elastic fibers. In contrast, fibroblasts from two cases of infantile GM1-gangliosidosis that bear nonsense mutations of the beta-galactosidase gene, as well as fibroblasts from four patients with Morquio B who had mutations causing deficiency in both forms of beta-galactosidase, did not assemble elastic fibers. We also demonstrated that S-Gal-deficient fibroblasts from patients with either GM1-gangliosidosis or Morquio B can acquire the S-Gal protein, produced by coculturing of Chinese hamster ovary cells permanently transected with S-Gal cDNA, resulting in improved deposition of elastic fibers. The present study provides a novel and natural model validating functional roles of S-Gal in elastogenesis and elucidates an association between impaired elastogenesis and the development of connective-tissue disorders in patients with Morquio B disease and in patients with an infantile form of GM1-gangliosidosis.  (+info)

(5/75) Saposins (sap) A and C activate the degradation of galactosylsphingosine.

As previously shown for [(3)H-galactosyl]ceramide, the breakdown of [(3)H-galactosyl]sphingosine was reduced in prosaposin-deficient skin fibroblast homogenates. Galactosylsphingosine hydrolysis was also deficient in cell homogenates from Krabbe's disease (beta-galactocerebrosidase-deficient) patients, but not acid beta-galactosidase-deficient patients. Moreover, hydrolysis of galactosylsphingosine in the prosaposin-deficient cell homogenates could be partially restored by adding pure saposin A or C, thereby identifying these saposins as essential facilitators of galactosylsphingosine hydrolysis. By contrast, saposins B and D had little effect on galactosylsphingosine hydrolysis in the prosaposin-deficient cells. The reduced galactosylsphingosine turnover in prosaposin-deficiency suggests that there could be a pathogenetic cerebral accumulation of galactosylsphingosine in this disorder.  (+info)

(6/75) Novel mutations (Asn 484 Lys, Thr 500 Ala, Gly 438 Glu) in Morquio B disease.

Primary deficiency of beta-galactosidase results in GM1 gangliosidosis and Morquio B disease. Of the more than 40 disease-causing mutations described in the Gal gene to date, about 75% are of the missense type and are scattered along the length of the gene. No single, major common mutation has been associated with GM1 gangliosidosis. However, a Trp 273 Leu mutation has been commonly found in the majority of patients with Morquio B disease defined genotypically to date. We now report three new mutations in three Morquio B patients where the Trp 273 Leu mutation is absent. Two of the mutations, C1502G (Asn 484 Lys) and A1548G (Thr 500 Ala), were found in twins (one male, one female) who display a mild form of Morquio B disease and keratan sulfate in the urine. In their fibroblasts, residual activity was 1.9% and 2.1% of controls. On Western blots, the 84-kDa precursor and the 64-kDa mature protein were barely detectable. The occurrence of a 45-kDa degradation product indicates that the mutated protein reached the lysosome but was abnormally processed. In the third case, we identified only a G1363A (Gly 438 Glu) mutation (a major deletion on the second allele has not been ruled out). This female patient too displays a very mild form of the disease with a residual activity of 5.7% of control values. In fibroblasts from this case, the 84-kDa precursor and the 45-kDa degradation product were present, while the mature 64-kDa form was barely detectable. The occurrence of these three mutations in the same area of the protein may define a domain involved in keratan sulfate degradation.  (+info)

(7/75) Upper airways abnormalities and tracheal problems in Morquio's disease.

Morquio's disease is a metabolic disorder that can cause various respiratory abnormalities. Patients who live into adulthood are likely to develop upper airway problems and respiratory failure. With advances in home ventilation, these patients are increasingly likely to be referred to specialist respiratory units. We describe our experiences with two such patients.  (+info)

(8/75) Mouse model of N-acetylgalactosamine-6-sulfate sulfatase deficiency (Galns-/-) produced by targeted disruption of the gene defective in Morquio A disease.

Mucopolysaccharidosis IVA is an autosomal recessive disorder caused by a deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS), a lysosomal enzyme required for the stepwise degradation of keratan sulfate (KS) and chondroitin-6-sulfate (C6S). To generate a model for studies of the pathophysiology and of potential therapies, we disrupted exon 2 of Galns, the homologous murine gene. Homozygous Galns-/- mice have no detectable GALNS enzyme activity and show increased urinary glycosaminoglycan (GAGs) levels. These mice accumulate GAGs in multiple tissues including liver, kidney, spleen, heart, brain and bone marrow. At 2 months old, lysosomal storage is present primarily within reticuloendothelial cells such as Kupffer cells and cells of the sinusoidal lining of the spleen. Additionally, by 12 months old, vacuolar change is observed in the visceral epithelial cells of glomeruli and cells at the base of heart valves but it is not present in parenchymal cells such as hepatocytes and renal tubular epithelial cells. In the brain, hippocampal and neocortical neurons and meningeal cells had lysosomal storage. KS and C6S were more abundant in the cytoplasm of corneal epithelial cells of Galns-/- mice compared with wild-type mice by immunohistochemistry. Radiographs revealed no change in the skeletal bones of mice up to 12 months old. Thus, targeted disruption of the murine Galns gene has produced a murine model, which shows visceral storage of GAGs but lacks the skeletal features. The complete absence of GALNS in mutant mice makes them useful for studies of pharmacokinetics and tissue targeting of recombinant GALNS designed for enzyme replacement.  (+info)



Hunter Syndrome


  • Mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome, is a member of a group of inherited metabolic disorders collectively termed the mucopolysaccharidoses (MPSs). (medscape.com)
  • The objective of this study is to determine the safety of once weekly dosing of idursulfase 0.5 mg/kg administered by intravenous (IV) infusion for male Hunter syndrome patients ≤ 5 years old. (clinicaltrials.gov)

patients


  • This multicenter, open-label extension study is designed to assess long-term efficacy and safety of 2.0 milligrams (mg)/kilogram(kg)/week of BMN 110 in patients diagnosed with Mucopolysaccharidosis IVA (MPS IVA). (clinicaltrials.gov)

type


  • Morquio syndrome is an autosomal recessive mucopolysaccharidosis (MPS) , type IV. (radiopaedia.org)