2018
Recommendations for clinical monitoring of patients with acid sphingomyelinase deficiency (ASMD)
Wasserstein M, Dionisi-Vici C, Giugliani R, Hwu WL, Lidove O, Lukacs Z, Mengel E, Mistry PK, Schuchman EH, McGovern M. Recommendations for clinical monitoring of patients with acid sphingomyelinase deficiency (ASMD). Molecular Genetics And Metabolism 2018, 126: 98-105. PMID: 30514648, PMCID: PMC7249497, DOI: 10.1016/j.ymgme.2018.11.014.Peer-Reviewed Original ResearchConceptsAcid sphingomyelinase deficiencyLifestyle modificationEvidence-informed consensus processMajor organ system involvementSphingomyelinase deficiencyAcid sphingomyelinaseLife style modificationDisease-specific treatmentOrgan system involvementInterdisciplinary clinical teamRare lysosomal storage diseaseEnzyme replacement therapyClinical assessment strategiesRecombinant human acid sphingomyelinaseLymph nodesDisease complicationsLiver diseasePatients' qualitySignificant morbiditySymptom managementSymptomatic treatmentClinical manifestationsReplacement therapyStyle modificationMultisystem involvement
2017
Consensus recommendation for a diagnostic guideline for acid sphingomyelinase deficiency
McGovern MM, Dionisi-Vici C, Giugliani R, Hwu P, Lidove O, Lukacs Z, Eugen Mengel K, Mistry PK, Schuchman EH, Wasserstein MP. Consensus recommendation for a diagnostic guideline for acid sphingomyelinase deficiency. Genetics In Medicine 2017, 19: 967-974. PMID: 28406489, PMCID: PMC5589980, DOI: 10.1038/gim.2017.7.Peer-Reviewed Original ResearchConceptsAcid sphingomyelinase deficiencyDiagnostic guidelinesSphingomyelinase deficiencyPrimary care providersTreatment/managementSpectrum of severityFatal lysosomal storage diseaseSymptom controlDisease specialistsNeurovisceral diseaseMultisystem involvementConsensus recommendationsLysosomal storage diseaseAmerican CollegeASMD patientsCare providersVisceral formEnzyme acid sphingomyelinaseMetabolic defectsEvidence baseRegular assessmentTarget tissuesStorage diseaseDisease managementLaboratory evaluation
2014
Glucocerebrosidase 2 gene deletion rescues type 1 Gaucher disease
Mistry PK, Liu J, Sun L, Chuang WL, Yuen T, Yang R, Lu P, Zhang K, Li J, Keutzer J, Stachnik A, Mennone A, Boyer JL, Jain D, Brady RO, New MI, Zaidi M. Glucocerebrosidase 2 gene deletion rescues type 1 Gaucher disease. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 4934-4939. PMID: 24639522, PMCID: PMC3977292, DOI: 10.1073/pnas.1400768111.Peer-Reviewed Original ResearchConceptsType 1 Gaucher's diseaseBone formation defectGaucher diseaseSerum ceramide levelsBone formation rateEnzyme replacement therapyViable therapeutic targetGD1 patientsGBA deficiencyEnhanced elevationTherapeutic targetBone volumeMononuclear phagocytesClinical phenotypeGBA geneConditional deletionBioactive lipidsSphingosine levelsDevelopment of inhibitorsCeramide levelsLysosomal glucocerebrosidasePatientsNanomolar concentrationsDiseaseMice
2012
Phenotype diversity in type 1 Gaucher disease: discovering the genetic basis of Gaucher disease/hematologic malignancy phenotype by individual genome analysis
Lo SM, Choi M, Liu J, Jain D, Boot RG, Kallemeijn WW, Aerts JM, Pashankar F, Kupfer GM, Mane S, Lifton RP, Mistry PK. Phenotype diversity in type 1 Gaucher disease: discovering the genetic basis of Gaucher disease/hematologic malignancy phenotype by individual genome analysis. Blood 2012, 119: 4731-4740. PMID: 22493294, PMCID: PMC3367875, DOI: 10.1182/blood-2011-10-386862.Peer-Reviewed Original ResearchConceptsGenome analysisGenetic basisCancer phenotypeWhole exome captureNovel mutationsGenomic analysisPhenotype annotationsPhenotype diversityParallel sequencingHomozygosity mappingT-cell acute lymphoblastic lymphomaGenetic modifiersNovel insightsGene sequencingGaucher diseaseMalignancy phenotypeMutationsLysosomal accumulationPhenotypeHomozygous novel mutationPathogenic mutationsGenesMSH6 proteinsSequencingEnzyme studiesGenome‐wide association study of N370S homozygous Gaucher disease reveals the candidacy of CLN8 gene as a genetic modifier contributing to extreme phenotypic variation
Zhang CK, Stein PB, Liu J, Wang Z, Yang R, Cho JH, Gregersen PK, Aerts JM, Zhao H, Pastores GM, Mistry PK. Genome‐wide association study of N370S homozygous Gaucher disease reveals the candidacy of CLN8 gene as a genetic modifier contributing to extreme phenotypic variation. American Journal Of Hematology 2012, 87: 377-383. PMID: 22388998, PMCID: PMC3684025, DOI: 10.1002/ajh.23118.Peer-Reviewed Original ResearchMeSH KeywordsAllelesCells, CulturedEpistasis, GeneticFemaleFibroblastsGaucher DiseaseGenome-Wide Association StudyGenotypeGermanyGlucosylceramidaseHomozygoteHumansJewsMacrophagesMaleMembrane ProteinsMiddle AgedMutation, MissensePhenotypePolymorphism, Single NucleotidePsychosineSeverity of Illness IndexConceptsGaucher diseaseType 1 Gaucher's diseaseMild Gaucher diseaseSevere disease categoryCandidate modifier genesGlucosylceramide-laden macrophagesAshkenazi Jewish patientsRisk allele ACultured skin fibroblastsEligible patientsMild diseaseOdds ratioSevere diseaseGBA1 mutationsPatientsJewish patientsDisease severityDisease categoriesCLN8 geneRisk allelesDiseaseN370S mutationSeveritySkin fibroblastsGenetic modifiers
2011
Elevated plasma glucosylsphingosine in Gaucher disease: relation to phenotype, storage cell markers, and therapeutic response
Dekker N, van Dussen L, Hollak CE, Overkleeft H, Scheij S, Ghauharali K, van Breemen MJ, Ferraz MJ, Groener JE, Maas M, Wijburg FA, Speijer D, Tylki-Szymanska A, Mistry PK, Boot RG, Aerts JM. Elevated plasma glucosylsphingosine in Gaucher disease: relation to phenotype, storage cell markers, and therapeutic response. Blood 2011, 118: e118-e127. PMID: 21868580, PMCID: PMC3685900, DOI: 10.1182/blood-2011-05-352971.Peer-Reviewed Original ResearchPulmonary vascular disease in Gaucher disease: clinical spectrum, determinants of phenotype and long‐term outcomes of therapy
Lo SM, Liu J, Chen F, Pastores GM, Knowles J, Boxer M, Aleck K, Mistry PK. Pulmonary vascular disease in Gaucher disease: clinical spectrum, determinants of phenotype and long‐term outcomes of therapy. Journal Of Inherited Metabolic Disease 2011, 34: 643-650. PMID: 21445609, PMCID: PMC3782382, DOI: 10.1007/s10545-011-9313-9.Peer-Reviewed Original ResearchConceptsPulmonary arterial hypertensionEnzyme replacement therapySeverity Score IndexHepatopulmonary syndromeLong-term outcomesGBA1 genotypeAdjuvant therapyPreponderance of femalesImiglucerase enzyme replacement therapyType 1 Gaucher diseaseDiagnosis of GD1Pulmonary vascular complicationsPulmonary vascular diseaseMedian age 12Spleen statusArterial hypertensionVascular complicationsPatient characteristicsConsecutive patientsInitial presentationMedian ageReplacement therapyClinical spectrumVascular diseasePatients
2010
Glucocerebrosidase gene-deficient mouse recapitulates Gaucher disease displaying cellular and molecular dysregulation beyond the macrophage
Mistry PK, Liu J, Yang M, Nottoli T, McGrath J, Jain D, Zhang K, Keutzer J, Chuang WL, Mehal WZ, Zhao H, Lin A, Mane S, Liu X, Peng YZ, Li JH, Agrawal M, Zhu LL, Blair HC, Robinson LJ, Iqbal J, Sun L, Zaidi M. Glucocerebrosidase gene-deficient mouse recapitulates Gaucher disease displaying cellular and molecular dysregulation beyond the macrophage. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 19473-19478. PMID: 20962279, PMCID: PMC2984187, DOI: 10.1073/pnas.1003308107.Peer-Reviewed Original ResearchConceptsType 1 Gaucher diseaseThymic T cellsGene-deficient miceOsteoblastic bone formationWorthwhile therapeutic targetDendritic cellsSevere osteoporosisAutoimmune diseasesWidespread dysfunctionCytokine measurementsT cellsCell lineagesParkinson's diseaseTherapeutic targetGBA1 geneMononuclear phagocytesGaucher diseaseGlucocerebrosidase deficiencyMolecular dysregulationDiseaseInhibitory effectBone formationMultiple cell lineagesMesenchymal cell lineagesMacrophagesMisdiagnosis of Niemann‐Pick disease type C as Gaucher disease
Lo SM, McNamara J, Seashore MR, Mistry PK. Misdiagnosis of Niemann‐Pick disease type C as Gaucher disease. Journal Of Inherited Metabolic Disease 2010, 33: 429-433. PMID: 20882348, PMCID: PMC3053412, DOI: 10.1007/s10545-010-9214-3.Peer-Reviewed Original ResearchMeSH Keywords1-DeoxynojirimycinAcid PhosphataseBiomarkersCarrier ProteinsCells, CulturedCholesterol EstersDiagnostic ErrorsDNA Mutational AnalysisEnzyme InhibitorsEnzyme Replacement TherapyEsterificationFemaleGaucher DiseaseGenetic Predisposition to DiseaseGlucosylceramidaseGlucosyltransferasesHepatomegalyHeterozygoteHexosaminidasesHumansInfantIntracellular Signaling Peptides and ProteinsIsoenzymesMembrane GlycoproteinsMutationNiemann-Pick C1 ProteinNiemann-Pick Disease, Type CPhenotypePredictive Value of TestsSplenomegalyTartrate-Resistant Acid PhosphataseUnnecessary ProceduresConceptsNiemann-Pick disease type CAcid β-glucosidase activityDisease type CGaucher diseaseSerum chitotriosidaseCholesterol esterificationDiagnosis of NPCEnzyme replacement therapySkin fibroblastsTartrate-resistant acid phosphataseType CFalse-positive testingCultured skin fibroblastsVisceral diseasePediatric patientsPrompt diagnosisDiagnostic delayInitial presentationInitial diagnosisReplacement therapyEffective therapyNeurological abnormalitiesCorrect diagnosisPositive testingHigh indexExpanding spectrum of the association between Type 1 Gaucher disease and cancers: A series of patients with up to 3 sequential cancers of multiple types—Correlation with genotype and phenotype
Lo SM, Stein P, Mullaly S, Bar M, Jain D, Pastores GM, Mistry PK. Expanding spectrum of the association between Type 1 Gaucher disease and cancers: A series of patients with up to 3 sequential cancers of multiple types—Correlation with genotype and phenotype. American Journal Of Hematology 2010, 85: 340-345. PMID: 20425796, PMCID: PMC2875938, DOI: 10.1002/ajh.21684.Peer-Reviewed Original ResearchConceptsType 1 Gaucher's diseaseGaucher diseaseMultiple myelomaMultiple malignanciesMultiple cancersEnzyme replacement therapy statusDiagnosis of GD1Initiation of ERTRate of splenectomySeries of patientsSystemic macrophage activationTypes of malignanciesLymphoma/leukemiaAccumulation of glucosylceramideAsplenic patientsGBA1 genotypeGD1 patientsSequential cancersFirst cancerSplenectomy statusTherapy statusNonhematologic malignanciesHematologic malignanciesIntact spleenProstate cancerHigh incidence of cholesterol gallstone disease in type 1 Gaucher disease: characterizing the biliary phenotype of type 1 Gaucher disease
Taddei TH, Dziura J, Chen S, Yang R, Hyogo H, Sullards C, Cohen DE, Pastores G, Mistry PK. High incidence of cholesterol gallstone disease in type 1 Gaucher disease: characterizing the biliary phenotype of type 1 Gaucher disease. Journal Of Inherited Metabolic Disease 2010, 33: 291-300. PMID: 20354791, PMCID: PMC3008397, DOI: 10.1007/s10545-010-9070-1.Peer-Reviewed Original ResearchConceptsPrevalence of gallstonesType 1 Gaucher diseaseBody mass indexBile lipid analysisGaucher diseaseLipoprotein cholesterolHigh low-density lipoprotein cholesterolLow high-density lipoprotein cholesterolHigh-density lipoprotein cholesterolLow-density lipoprotein cholesterolMultiple logistic regression analysisType 1 Gaucher's diseaseBile lipid compositionBiliary lipid secretionCholesterol gallstone diseaseLogistic regression analysisMetabolic syndromeGallstone diseaseLDL cholesterolStudy cohortLipoprotein profileMass indexFemale sexBile compositionBiliary lipidsThe risk of Parkinson's disease in type 1 Gaucher disease
Bultron G, Kacena K, Pearson D, Boxer M, Yang R, Sathe S, Pastores G, Mistry PK. The risk of Parkinson's disease in type 1 Gaucher disease. Journal Of Inherited Metabolic Disease 2010, 33: 167-173. PMID: 20177787, PMCID: PMC2887303, DOI: 10.1007/s10545-010-9055-0.Peer-Reviewed Original ResearchConceptsParkinson's diseaseGeneral populationGaucher diseaseRisk of PDType 1 Gaucher diseaseType 1 Gaucher's diseaseIdiopathic Parkinson's diseaseLife-time riskFirst-degree relativesParkinson's disease phenotypeLife-threatening diseaseDisease phenotypeGenetic risk factorsMagnitude of riskAvascular osteonecrosisClinical spectrumParkinsonian syndromesRisk ratioSeverity scoreRisk factorsDegree relativesHigh riskHigh incidencePD phenotypePatients
2009
The underrecognized progressive nature of N370S Gaucher disease and assessment of cancer risk in 403 patients
Taddei TH, Kacena KA, Yang M, Yang R, Malhotra A, Boxer M, Aleck KA, Rennert G, Pastores GM, Mistry PK. The underrecognized progressive nature of N370S Gaucher disease and assessment of cancer risk in 403 patients. American Journal Of Hematology 2009, 84: 208-214. PMID: 19260119, PMCID: PMC3008404, DOI: 10.1002/ajh.21362.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAge of OnsetBone Diseases, MetabolicChildCross-Sectional StudiesDisease ProgressionFemaleGaucher DiseaseGenetic HeterogeneityGenetic Predisposition to DiseaseGenotypeGlucosylceramidaseHumansHypergammaglobulinemiaIncidenceJewsMaleMiddle AgedMultiple MyelomaMutation, MissenseNeoplasmsOrgan SpecificityPhenotypePoint MutationRiskVisceraYoung AdultConceptsMultiple myelomaGaucher diseaseSkeletal diseaseRelative riskCancer riskType 1 Gaucher's diseaseCommon lysosomal storage disorderCross-sectional studyOverall cancer riskProgressive skeletal diseaseAdaptive immune systemLysosomal storage disorderAdult patientsEntire cohortLifetime riskNatural courseHematologic malignanciesRelative sparingHematologic diseasesHigh riskHigh incidencePatientsGBA1 geneHomozygous patientsImmune system
2007
Buts thérapeutiques dans la maladie de Gaucher Therapeutic objectives in Gaucher disease
Mistry P, Germain D. Buts thérapeutiques dans la maladie de Gaucher Therapeutic objectives in Gaucher disease. La Revue De Médecine Interne 2007, 28: 171-175. PMID: 18228683, DOI: 10.1016/s0248-8663(07)78876-8.Peer-Reviewed Original ResearchConceptsGaucher diseaseLife-threatening complicationsStandard of careMaximal clinical benefitRemarkable safety profileTreatment of GDQuality of lifeType 1 GDBone crisesLifelong treatmentClinical benefitSafety profileAsymptomatic phaseTherapeutic goalsDisease evolutionTherapeutic objectivesCareful monitoringLa maladieSkeletal damageNorth American expertsDiseaseDisease phenotypePatientsTreatmentOptimal time
2006
Phenotype variations in Gaucher disease
Mistry P, Germain DP. Phenotype variations in Gaucher disease. La Revue De Médecine Interne 2006, 27: s3-s6. PMID: 16644399, DOI: 10.1016/s0248-8663(06)80002-0.Peer-Reviewed Original ResearchConceptsGaucher diseaseClinical manifestationsMajority of patientsRate of progressionGaucher phenotypeHigh inter-individual variabilityGenotype-phenotype correlationDevastating complicationInter-individual variabilityBlood countDisease compartmentsNatural historyDiseaseGlucocerebrosidase activityN370S mutationGenetic modifiersMolecular diagnosisDiagnosisSeverityManifestationsTherapeutic goals in Gaucher disease
Mistry P, Germain DP. Therapeutic goals in Gaucher disease. La Revue De Médecine Interne 2006, 27: s30-s33. PMID: 16644400, DOI: 10.1016/s0248-8663(06)80009-3.Peer-Reviewed Original ResearchConceptsGaucher diseaseTherapeutic goalsType 1 Gaucher diseaseLong-life treatmentLife-threatening complicationsStandard of careRemarkable safety profileQuality of lifeBone crisesPrevent complicationsSafety profileAsymptomatic phaseDisease evolutionCareful monitoringDiseaseSkeletal damageComplicationsPatientsGaucher phenotypeTreatmentOptimal timeTolerabilityAmerican expertsSeverityCareEnzyme replacement therapy and bony changes in Egyptian paediatric Gaucher disease patients
El‐Beshlawy A, Ragab L, Youssry I, Yakout K, El‐Kiki H, Eid K, Mansour IM, El‐Hamid S, Yang M, Mistry PK. Enzyme replacement therapy and bony changes in Egyptian paediatric Gaucher disease patients. Journal Of Inherited Metabolic Disease 2006, 29: 92-98. PMID: 16601874, DOI: 10.1007/s10545-006-0121-6.Peer-Reviewed Original ResearchConceptsMagnetic resonance imagingBone involvementSkeletal diseaseGaucher diseaseBone painGBA genotypeReplacement therapySkeletal involvementBone diseaseComplete symptomatic remissionEarly skeletal involvementMonths of ERTAbnormal radiographic findingsCorrelation of severityGaucher disease patientsEnzyme replacement therapyPaucity of dataCrippling complicationsGenotype-phenotype correlationComplete remissionVisceral diseaseVisceral involvementRadiological manifestationsRadiographic findingsPatient population
2002
Pulmonary hypertension in type 1 Gaucher’s disease: genetic and epigenetic determinants of phenotype and response to therapy
Mistry PK, Sirrs S, Chan A, Pritzker MR, Duffy TP, Grace ME, Meeker DP, Goldman ME. Pulmonary hypertension in type 1 Gaucher’s disease: genetic and epigenetic determinants of phenotype and response to therapy. Molecular Genetics And Metabolism 2002, 77: 91-98. PMID: 12359135, DOI: 10.1016/s1096-7192(02)00122-1.Peer-Reviewed Original ResearchConceptsType 1 Gaucher's diseaseSevere pulmonary hypertensionLife-threatening pulmonary hypertensionRight ventricular systolic pressurePulmonary hypertensionGaucher diseaseAsymptomatic pulmonary hypertensionCharacteristics of patientsHigh-risk patientsVentricular systolic pressureEnzyme gene polymorphismACE I alleleAdditional genetic factorsLung transplantationUntreated patientsTransplant candidatesConsecutive patientsSystolic pressureTertiary referralDoppler echocardiographyReplacement therapyClinical spectrumPoor complianceGD patientsGBA mutations
2000
The Gaucher Registry: Demographics and Disease Characteristics of 1698 Patients With Gaucher Disease
Charrow J, Andersson HC, Kaplan P, Kolodny EH, Mistry P, Pastores G, Rosenbloom BE, Scott CR, Wappner RS, Weinreb NJ, Zimran A. The Gaucher Registry: Demographics and Disease Characteristics of 1698 Patients With Gaucher Disease. JAMA Internal Medicine 2000, 160: 2835-2843. PMID: 11025794, DOI: 10.1001/archinte.160.18.2835.Peer-Reviewed Original ResearchConceptsGaucher RegistryGaucher diseaseAsplenic patientsStandardized data collection formType 1 Gaucher diseaseRadiological bone diseaseN370S/N370S genotypeEnzyme replacement therapyData collection formBone painClinical characteristicsMost patientsOngoing registryOptimal therapyReplacement therapyClinical spectrumDisease characteristicsSpecific therapyLiver volumeBone diseasePatientsLarger sample sizeType 2Collection formRetrospective data
1993
The glucocerebrosidase locus in Gaucher's disease: molecular analysis of a lysosomal enzyme.
Mistry PK, Cox TM. The glucocerebrosidase locus in Gaucher's disease: molecular analysis of a lysosomal enzyme. Journal Of Medical Genetics 1993, 30: 889. PMID: 8301642, PMCID: PMC1016594, DOI: 10.1136/jmg.30.11.889.Peer-Reviewed Original Research