Effect of Hunter disease (mucopolysaccharidosis type II) mutations on molecular phenotypes of iduronate-2-sulfatase: enzymatic activity, protein processing and structural analysis.

Abstract:

:Mucopolysaccharidosis II (Hunter disease), a lysosomal storage disorder caused by a deficiency of iduronate-2-sulfatase (IDS), has variable clinical phenotypes. Nearly 300 different mutations have been identified in the IDS gene from patients with Hunter disease, but the correlation between the genotype and phenotype has remained unclear. We studied the characteristics of 11 missense mutations, which were detected in the patients or artificially introduced, using stable expression experiments and structural analysis. The mutants found in the attenuated phenotype showed considerable residual activity (0.2-2.4% of the wild-type IDS activity) and those in the severe phenotype had no activity. In immunoblot analysis, both the 73-75 kDa precursor and processed forms were detected in the expression of 'attenuated' mutants (R48P, A85T and W337R) and the artificial active site mutants (C84S, C84T). The 73-75 kDa initial precursor was detected in the 'severe' mutants (P86L, S333L, S349I, R468Q, R468L). The truncated 68 kDa precursor form was synthesized in the Q531X mutant. The results of immunoblotting indicated rapid degradation and/or insufficiency in processing as a result of structural alteration of the IDS protein. A combination of analyses of genotype and molecular phenotypes, including enzyme activity, protein processing and structural analysis with an engineered reference protein, could provide an avenue to understanding the molecular mechanism of the disease and could give a useful tool for the evaluation of possible therapeutic chemical compounds.

journal_name

J Inherit Metab Dis

authors

Sukegawa-Hayasaka K,Kato Z,Nakamura H,Tomatsu S,Fukao T,Kuwata K,Orii T,Kondo N

doi

10.1007/s10545-006-0440-7

subject

Has Abstract

pub_date

2006-12-01 00:00:00

pages

755-61

issue

6

eissn

0141-8955

issn

1573-2665

journal_volume

29

pub_type

杂志文章
  • Some nutritional aspects of trace metals.

    abstract::A brief outline of the known biochemical roles of manganese and chromium is given before the problems of determining human trace metal status are discussed. The factors predisposing to trace metal deficiency are reviewed but particular emphasis is placed upon those which alter the bioavailability of essential trace me...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章,评审

    doi:10.1007/BF01811319

    authors: Aggett PJ,Davies NT

    更新日期:1983-01-01 00:00:00

  • Ear symptoms in children with Fabry disease: data from the Fabry Outcome Survey.

    abstract:BACKGROUND:Hearing loss and tinnitus are common symptoms in Fabry disease and increase in prevalence with age. This study aimed to provide an epidemiological description of hearing impairment and tinnitus in children with Fabry disease in the Fabry Outcome Survey (FOS), an international database to assess the natural h...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章,多中心研究

    doi:10.1007/s10545-009-1290-x

    authors: Keilmann A,Hajioff D,Ramaswami U,FOS Investigators.

    更新日期:2009-12-01 00:00:00

  • Toward understanding tissue-specific symptoms in dolichol-phosphate-mannose synthesis disorders; insight from DPM3-CDG.

    abstract::The congenital disorders of glycosylation (CDG) are inborn errors of metabolism with a great genetic heterogeneity. Most CDG are caused by defects in the N-glycan biosynthesis, leading to multisystem phenotypes. However, the occurrence of tissue-restricted clinical symptoms in the various defects in dolichol-phosphate...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章

    doi:10.1002/jimd.12095

    authors: van Tol W,Michelakakis H,Georgiadou E,van den Bergh P,Moraitou M,Papadimas GK,Papadopoulos C,Huijben K,Alsady M,Willemsen MA,Lefeber DJ

    更新日期:2019-09-01 00:00:00

  • The X chromosome in development in mouse and man.

    abstract::In mammals, dosage compensation for X-linked genes between males and females is achieved by the inactivation of one of the X chromosomes in females. The inactivation event occurs early in development in all cells of the female mouse embryo and is stable and heritable in somatic cells. However, in the primordial germ c...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章,评审

    doi:10.1007/BF01799608

    authors: Monk M

    更新日期:1992-01-01 00:00:00

  • Aspartylglycosaminuria: an inborn error of glycoprotein catabolism.

    abstract::Aspartylglycosaminuria (AGU, McKusick 20840) is a metabolic disorder affecting the catabolism of glycoproteins. It was first described in 1967, by Jenner and Pollitt, in two mentally retarded English siblings. Subsequently several cases were reported from Finland (Palo and Mattsson, 1970; Autio, 1972; Autio et al., 19...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章,评审

    doi:10.1007/BF02179139

    authors: Maury CP

    更新日期:1982-01-01 00:00:00

  • Nitisinone causes acquired tyrosinosis in alkaptonuria.

    abstract::For over two decades, nitisinone (NTBC) has been successfully used to manipulate the tyrosine degradation pathway and save the lives of many children with hereditary tyrosinaemia type 1. More recently, NTBC has been used to halt homogentisic acid accumulation in alkaptonuria (AKU) with evidence suggesting its efficacy...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章

    doi:10.1002/jimd.12229

    authors: Khedr M,Cooper MS,Hughes AT,Milan AM,Davison AS,Norman BP,Sutherland H,Jarvis JC,Fitzgerald R,Markinson L,Psarelli EE,Ghane P,Deutz NEP,Gallagher JA,Ranganath LR

    更新日期:2020-09-01 00:00:00

  • Profound biotinidase deficiency: a rare disease among native Swedes.

    abstract::Biotinidase deficiency is an autosomal recessive metabolic disorder included in many newborn screening programmes. Prior to the introduction of screening for biotinidase deficiency in Sweden in 2002, the disorder was almost unknown, with only one case diagnosed clinically. Biotinidase activity was measured in dried bl...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章

    doi:10.1007/s10545-010-9065-y

    authors: Ohlsson A,Guthenberg C,Holme E,von Döbeln U

    更新日期:2010-12-01 00:00:00

  • Hearing loss in children with Fabry disease.

    abstract:BACKGROUND:Hearing loss (HL) is a well-known feature of Fabry disease (FD). Its presence and characteristics have mainly been studied in adult patients, while only limited data are available on the presence and degree of HL in children with FD. This prompted us to study hearing sensitivity in pediatric FD patients. ME...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章

    doi:10.1007/s10545-017-0051-5

    authors: Suntjens E,Dreschler WA,Hess-Erga J,Skrunes R,Wijburg FA,Linthorst GE,Tøndel C,Biegstraaten M

    更新日期:2017-09-01 00:00:00

  • Renal failure in adult patients with hereditary tyrosinaemia type I.

    abstract::An adult patient with hereditary tyrosinaemia type I who developed renal failure is reported. She received a renal transplant at the age of 23 years. In childhood her kidney disease was dominated by multiple tubular defects with resulting hypophosphataemic rickets. Metabolic acidosis was the most prominent feature in ...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章

    doi:10.1007/BF01804389

    authors: Kvittingen EA,Talseth T,Halvorsen S,Jakobs C,Hovig T,Flatmark A

    更新日期:1991-01-01 00:00:00

  • Regulatory environment for novel therapeutic development in mitochondrial diseases.

    abstract::At present, there is just one approved therapy for patients with mitochondrial diseases in Europe, another in Japan, and none in the United States. These facts reveal an important and significant unmet need for approved therapies for these debilitating and often fatal disorders. To fill this need, it is critical for c...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章,评审

    doi:10.1002/jimd.12353

    authors: Hirano M,Berardo A,Barca E,Emmanuele V,Quinzii C,Simpson CV,Engelstad K,Rosales XQ,Thompson JLP

    更新日期:2020-12-24 00:00:00

  • Clinical and molecular heterogeneity of cytochrome c oxidase deficiency in the newborn.

    abstract::We report 8 cases of severe cytochrome c oxidase deficiency with onset in the neonatal period. Clinical symptoms were heterogeneous: antenatal cerebral malformations, neurological distress with ketoacidosis, severe myopathy, or isolated respiratory control failure. Lactic acid was elevated in blood and/or CSF in 7 cas...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章

    doi:10.1007/BF01799256

    authors: Lombes A,Romero NB,Touati G,Frachon P,Cheval MA,Giraud M,Simon D,Ogier de Baulny H

    更新日期:1996-01-01 00:00:00

  • Scheie syndrome: enzyme replacement therapy does not prevent progression of cervical myelopathy due to spinal cord compression.

    abstract::Hurler-Scheie syndrome is caused by alpha-l-iduronidase deficiency. Enzyme replacement therapy (ERT) can improve physical capacity and reduces organomegaly. However, the effect on bradytrophic connective tissue is limited. As intravenously administered enzyme cannot cross the blood-brain barrier, the therapy of choice...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章

    doi:10.1007/s10545-009-1265-y

    authors: Illsinger S,Lücke T,Hartmann H,Mengel E,Müller-Forell W,Donnerstag F,Das AM

    更新日期:2009-12-01 00:00:00

  • Simple method for detection of mutations causing hereditary fructose intolerance.

    abstract::Aldolase B is critical for sugar metabolism, and a catalytic deficiency due to mutations in its gene may result in hereditary fructose intolerance (HFI) syndrome, with hypoglycaemia and severe abdominal symptoms. This report describes two cases of HFI, which were identified by intravenous fructose tolerance test and a...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章

    doi:10.1023/a:1022043307569

    authors: Kullberg-Lindh C,Hannoun C,Lindh M

    更新日期:2002-11-01 00:00:00

  • Adenosine, dopamine and serotonin receptors imbalance in lymphocytes of Lesch-Nyhan patients.

    abstract::Lesch-Nyhan disease (LND) is caused by complete deficiency of the hypoxanthine-guanine phosphoribosyltransferase enzyme. It is characterized by overproduction of uric acid, jointly with severe motor disability and self-injurious behaviour which physiopathology is unknown. These neurological manifestations suggest a dy...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章

    doi:10.1007/s10545-012-9470-5

    authors: García MG,Puig JG,Torres RJ

    更新日期:2012-11-01 00:00:00

  • Regression of neuropsychological deficits in early-treated phenylketonurics during adolescence.

    abstract::Even early-treated phenylketonuric patients suffer from phenylalanine-associated (mild) neuropsychological impairment. To date it is still unclear whether patients' deficits show a progression on ageing. This unsolved question seems to be an important aspect in the still ongoing debate about how long and how strictly ...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章

    doi:10.1023/a:1005587915468

    authors: Weglage J,Pietsch M,Denecke J,Sprinz A,Feldmann R,Grenzebach M,Ullrich K

    更新日期:1999-08-01 00:00:00

  • Quantitative analysis of disaccharides in the urine of beta-mannosidosis patients.

    abstract::Until recently, there have not been any confirmed reports of beta-mannosidase deficiency in man. We have now analysed urine from two patients with confirmed beta-mannosidase deficiency and have found Man-beta(1-4)GlcNAc concentrations of 65 and 73 mg/mmol creatinine. These levels are at least 12 times higher than thos...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章

    doi:10.1007/BF01799685

    authors: Tjoa S,Wenger DA,Fennessey PV

    更新日期:1990-01-01 00:00:00

  • Techniques for studying hepatic metabolism in vivo.

    abstract::Techniques for studying metabolic events in vivo in patients with inborn errors are reviewed. Loading or provocation tests that have been used widely are insensitive and frequently non-specific. Compounds labelled with stable isotopes can be used to study enzyme kinetics and substrate turnover, providing more detailed...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章,评审

    doi:10.1007/BF01797925

    authors: Leonard JV,Thompson GN

    更新日期:1991-01-01 00:00:00

  • A new French-Canadian family affected by hyperargininaemia.

    abstract::A new French-Canadian family from the province of Quebec is reported, in which a male child was diagnosed as hyperargininaemic after showing positive tests for cystinuria on neonatal screening. The child has no residual activity of erythrocyte arginase, and a plasma arginine level of 633 mumol/l. Both parents have 32-...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章

    doi:10.1007/BF02310878

    authors: Qureshi IA,Letarte J,Ouellet R,Larochelle J,Lemieux B

    更新日期:1983-01-01 00:00:00

  • A survey of Japanese patients with Menkes disease from 1990 to 2003: incidence and early signs before typical symptomatic onset, pointing the way to earlier diagnosis.

    abstract::Menkes disease (MNK) is a lethal, X-linked recessive disorder of copper metabolism dominated by neurodegenerative symptoms and connective tissue disturbances. The incidence of MNK in Asia is not known. Most patients die by the age of 3 years if adequate treatment is not carried out. Early parenteral administration of ...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章

    doi:10.1007/s10545-005-0473-3

    authors: Gu YH,Kodama H,Shiga K,Nakata S,Yanagawa Y,Ozawa H

    更新日期:2005-01-01 00:00:00

  • Contribution of tandem mass spectrometry to the diagnosis of lysosomal storage disorders.

    abstract::Tandem mass spectrometry (MS/MS) is a highly sensitive and specific technique. Thanks to the development of triple quadrupole analyzers, it is becoming more widely used in laboratories working in the field of inborn errors of metabolism. We review here the state of the art of this technique applied to the diagnosis of...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章,评审

    doi:10.1007/s10545-017-0126-3

    authors: Piraud M,Pettazzoni M,Lavoie P,Ruet S,Pagan C,Cheillan D,Latour P,Vianey-Saban C,Auray-Blais C,Froissart R

    更新日期:2018-05-01 00:00:00

  • Standardized loading test with protein for the differentiation of phenylketonuria from hyperphenylalaninaemia.

    abstract::Eighty-nine protein-loading tests were performed in 80 patients with an increased blood phenylalanine concentration. The amount of protein corresponding to 0.18 g phenylalanine/kg body weight per day was calculated and given for 3 days, during which time eight phenylalanine and eight tyrosine blood concentrations were...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章

    doi:10.1007/BF01799751

    authors: Lutz P,Schmidt H,Frey G,Bickel H

    更新日期:1982-01-01 00:00:00

  • Defect in proline synthesis: pyrroline-5-carboxylate reductase 1 deficiency leads to a complex clinical phenotype with collagen and elastin abnormalities.

    abstract::Pyrroline-5-carboxylate reductase 1 (PYCR1) catalyzes the last step in proline synthesis. Deficiency of PYCR1, caused by a defect in PYCR1, was recently described in patients with cutis laxa, intrauterine growth retardation, developmental dysplasia of the hips and mental retardation. In this paper, we describe additio...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章

    doi:10.1007/s10545-011-9319-3

    authors: Kretz R,Bozorgmehr B,Kariminejad MH,Rohrbach M,Hausser I,Baumer A,Baumgartner M,Giunta C,Kariminejad A,Häberle J

    更新日期:2011-06-01 00:00:00

  • Tyrosine monitoring in children with early and continuously treated phenylketonuria: results of an international practice survey.

    abstract::Investigations into the biochemical markers associated with executive function (EF) impairment in children with early and continuously treated phenylketonuria (ECT-PKU) remain largely phenylalanine-only focused, despite experimental data showing that a high phenylalanine:tyrosine (phe:tyr) ratio is more strongly assoc...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章,多中心研究

    doi:10.1007/s10545-010-9211-6

    authors: Sharman R,Sullivan KA,Young RM,McGill JJ

    更新日期:2010-12-01 00:00:00

  • Outcome of enzyme replacement therapy in patients with Gaucher disease type I. The Romanian experience.

    abstract:AIM:This study reports the first evaluation of therapeutic response in Romanian patients with Gaucher disease type I, after therapy with Cerezyme recently became available in our country. PATIENTS AND METHODS:24 patients (11-50 years) received Cerezyme 20-60 U/kg every two weeks for at least 18 months. Haemoglobin, pl...

    journal_title:Journal of inherited metabolic disease

    pub_type: 临床试验,杂志文章

    doi:10.1007/s10545-007-0621-z

    authors: Grigorescu Sido P,Drugan C,Cret V,Al-Kzouz C,Denes C,Coldea C,Zimmermann A

    更新日期:2007-10-01 00:00:00

  • Long-term metabolic follow-up and clinical outcome of 35 patients with maple syrup urine disease.

    abstract:BACKGROUND:Maple syrup urine disease (MSUD) is a rare disease that requires a protein-restricted diet for successful management. Little is known, however, about the psychosocial outcome of MSUD patients. This study investigates the relationship between metabolic and clinical parameters and psychosocial outcomes in a co...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章

    doi:10.1007/s10545-017-0083-x

    authors: Abi-Wardé MT,Roda C,Arnoux JB,Servais A,Habarou F,Brassier A,Pontoizeau C,Barbier V,Bayart M,Leboeuf V,Chadefaux-Vekemans B,Dubois S,Assoun M,Belloche C,Alili JM,Husson MC,Lesage F,Dupic L,Theuil B,Ottolenghi C,de

    更新日期:2017-11-01 00:00:00

  • Pattern reversal visual evoked potentials in phenylketonuria.

    abstract::The pathogenesis of brain dysfunction in phenylketonuria (PKU) is still under investigation. Hyperphenylalaninaemia results in increased turnover of myelin. In order to demonstrate the derangement of myelinization in PKU we studied the visual evoked potentials (VEP) in 14 PKU patients and in 20 normal subjects. VEP fi...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章

    doi:10.1007/BF01800430

    authors: Giovannini M,Valsasina R,Villani R,Ducati A,Riva E,Landi A,Longhi R

    更新日期:1988-01-01 00:00:00

  • Successful allogeneic bone marrow transplant for Niemann-Pick disease type C2 is likely to be associated with a severe 'graft versus substrate' effect.

    abstract::Niemann-Pick disease type C2 (NPC2) is caused by the inherited deficiency of a lysosomal cholesterol transport protein, NPC2 protein. Many cases of NPC2 present in early infancy with inflammatory lung disease, with subsequent severe neurological disease and death in early childhood. This disease is theoretically corre...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章

    doi:10.1007/s10545-010-9060-3

    authors: Bonney DK,O'Meara A,Shabani A,Imrie J,Bigger BW,Jones S,Wraith JE,Wynn RF

    更新日期:2010-12-01 00:00:00

  • Sucrase-isomaltase and cystic fibrosis.

    abstract::The intestinal microvillar enzyme complex sucrase-isomaltase has been studied in cystic fibrosis and control ileum. A number of biochemical parameters of the enzyme in ileum homogenates have been determined. Both solubilized as well as membrane-bound sucrase-isomaltase were analyzed with respect to their reaction with...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章

    doi:10.1007/BF01805427

    authors: Sips HJ,Claass AH,van Dongen JM,Willemsen R,Hoogeveen AT,Galjaard H,Sinaasappel M,Hauri HP,Sterchi EE

    更新日期:1985-01-01 00:00:00

  • The potential of dietary treatment in patients with glycogen storage disease type IV.

    abstract::There is paucity of literature on dietary treatment in glycogen storage disease (GSD) type IV and formal guidelines are not available. Traditionally, liver transplantation was considered the only treatment option for GSD IV. In light of the success of dietary treatment for the other hepatic forms of GSD, we have initi...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章

    doi:10.1002/jimd.12339

    authors: Derks TGJ,Peeks F,de Boer F,Fokkert-Wilts M,van der Doef HPJ,van den Heuvel MC,Szymańska E,Rokicki D,Ryan PT,Weinstein DA

    更新日期:2020-12-17 00:00:00

  • Coenzyme Q(10) is decreased in fibroblasts of patients with methylmalonic aciduria but not in mevalonic aciduria.

    abstract::The content of coenzyme Q(10) (CoQ(10)) was examined in skin fibroblasts of 10 patients with mevalonic aciduria (MVA) and of 22 patients with methylmalonic aciduria (MMA). Patients with these inborn errors of metabolism are thought to be at risk for CoQ(10) depletion either by direct inhibition of the proximal pathway...

    journal_title:Journal of inherited metabolic disease

    pub_type: 杂志文章

    doi:10.1007/s10545-009-1150-8

    authors: Haas D,Niklowitz P,Hörster F,Baumgartner ER,Prasad C,Rodenburg RJ,Hoffmann GF,Menke T,Okun JG

    更新日期:2009-08-01 00:00:00