2021
The clinical spectrum of SARS-CoV-2 infection in Gaucher disease: Effect of both a pandemic and a rare disease that disrupts the immune system
Narayanan P, Nair S, Balwani M, Malinis M, Mistry P. The clinical spectrum of SARS-CoV-2 infection in Gaucher disease: Effect of both a pandemic and a rare disease that disrupts the immune system. Molecular Genetics And Metabolism 2021, 135: 115-121. PMID: 34412940, PMCID: PMC8361210, DOI: 10.1016/j.ymgme.2021.08.004.Peer-Reviewed Case Reports and Technical NotesConceptsSARS-CoV-2 infectionType 1 Gaucher diseaseSARS-CoV-2Gaucher diseaseRare diseaseCOVID-19Immune system dysfunctionRare disease populationMedian agePediatric patientsCase seriesFemale patientsAdverse outcomesClinical spectrumIntensive careGD patientsSystem dysfunctionRetrospective analysisDisease populationHigh riskGeneral populationPatientsImmune systemDiseaseSimilar frequencyClinical outcomes after 4.5 years of eliglustat therapy for Gaucher disease type 1: Phase 3 ENGAGE trial final results
Mistry PK, Lukina E, Turkia H, Shankar SP, Feldman H, Ghosn M, Mehta A, Packman S, Lau H, Petakov M, Assouline S, Balwani M, Danda S, Hadjiev E, Ortega A, Foster MC, Gaemers SJM, Peterschmitt MJ. Clinical outcomes after 4.5 years of eliglustat therapy for Gaucher disease type 1: Phase 3 ENGAGE trial final results. American Journal Of Hematology 2021, 96: 1156-1165. PMID: 34161616, PMCID: PMC8457136, DOI: 10.1002/ajh.26276.Peer-Reviewed Original ResearchConceptsDisease type 1Gaucher disease type 1Type 1Disease manifestationsENGAGE trialOpen-label extension periodOral substrate reduction therapySpine T-scoreYears of treatmentSubstrate reduction therapyMagnitude of improvementEliglustat therapyMean hemoglobinUntreated patientsAdverse eventsTrial cohortClinical outcomesEligible adultsPlatelet countUntreated adultsSpleen volumeLiver volumeHematologic parametersReduction therapyPatientsGaucher disease type 1 patients from the ICGG Gaucher Registry sustain initial clinical improvements during twenty years of imiglucerase treatment
Weinreb NJ, Camelo JS, Charrow J, McClain MR, Mistry P, Belmatoug N, investigators F. Gaucher disease type 1 patients from the ICGG Gaucher Registry sustain initial clinical improvements during twenty years of imiglucerase treatment. Molecular Genetics And Metabolism 2021, 132: 100-111. PMID: 33485799, DOI: 10.1016/j.ymgme.2020.12.295.Peer-Reviewed Original ResearchConceptsBone painNon-splenectomized patientsType 1 patientsBone crisesPlatelet countLiver volumeSubset analysisBody mass index (BMI) outcomesGaucher diseaseEarly treatment yearsInitial clinical improvementDifferent patient subsetsPre-treatment baselineLong-term treatmentEnzyme replacement therapyICGG Gaucher RegistryGD type 1 patientsImiglucerase treatmentAdult patientsClinical improvementSplenectomy statusGaucher RegistryPatient subsetsTreatment initiationNormal weight
2020
Gaucher disease and SARS-CoV-2 infection: Experience from 181 patients in New York
Fierro L, Nesheiwat N, Naik H, Narayanan P, Mistry PK, Balwani M. Gaucher disease and SARS-CoV-2 infection: Experience from 181 patients in New York. Molecular Genetics And Metabolism 2020, 132: 44-48. PMID: 33353808, PMCID: PMC7834197, DOI: 10.1016/j.ymgme.2020.12.288.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionSARS-CoV-2Gaucher diseaseAcid β-glucosidase activitySARS-CoV-2 nucleic acidCOVID-19-specific treatmentsMajority of patientsChronic inflammatory stateCross-sectional studyHigher antibody responseCOVID-19 symptomsCOVID-19 exposureRare disease populationSubset of adultsGBA genotypeQuantitative titersPrior splenectomyAntibody testingHigh morbidityImmune activationInflammatory statePrimary exposureAntibody responseChronic disordersMale genderReal‐world effectiveness of eliglustat in treatment‐naïve and switch patients enrolled in the International Collaborative Gaucher Group Gaucher Registry
Mistry PK, Balwani M, Charrow J, Kishnani P, Niederau C, Underhill LH, McClain MR. Real‐world effectiveness of eliglustat in treatment‐naïve and switch patients enrolled in the International Collaborative Gaucher Group Gaucher Registry. American Journal Of Hematology 2020, 95: 1038-1046. PMID: 32438452, PMCID: PMC7497238, DOI: 10.1002/ajh.25875.Peer-Reviewed Original ResearchConceptsSpine Z-scoreInternational Collaborative Gaucher Group Gaucher RegistryGaucher disease type 1Treatment-naïve patientsSwitch patientsMean hemoglobinPlatelet countLiver volumeZ-scoreGaucher RegistrySpleen volumeLumbar spine Z-scoreFirst-line oral therapyCYP2D6 metabolizer phenotypeMean platelet countReal-world effectivenessClinical trial resultsDisease type 1Real-world outcomesEliglustat therapyGD1 patientsOral therapyTreatment-naïveMost patientsERT patientsGlucosylsphingosine but not Saposin C, is the target antigen in Gaucher disease-associated gammopathy
Nair S, Bar N, Xu ML, Dhodapkar M, Mistry PK. Glucosylsphingosine but not Saposin C, is the target antigen in Gaucher disease-associated gammopathy. Molecular Genetics And Metabolism 2020, 129: 286-291. PMID: 32044242, PMCID: PMC8223251, DOI: 10.1016/j.ymgme.2020.01.009.Peer-Reviewed Original ResearchConceptsGaucher disease type 1Monoclonal gammopathyAntigenic targetsClonal immunoglobulinDisease type 1B cell activationAccumulation of glucosylceramideGD1 patientsImmunogenic lipidsMetabolic inflammationMultiple myelomaGD patientsHigh riskTarget antigenCell activationImmunoglobulin typeGammopathyType 1PatientsGenetic deficiencyAge-related phenotypesSaposin CClonal IgLysosomal glucocerebrosidaseGlcSph
2019
Etiology of cirrhosis in the young
Olave MC, Gurung A, Mistry PK, Kakar S, Yeh M, Xu M, Wu TT, Torbenson M, Jain D. Etiology of cirrhosis in the young. Human Pathology 2019, 96: 96-103. PMID: 31698008, DOI: 10.1016/j.humpath.2019.09.015.Peer-Reviewed Original ResearchConceptsEtiology of cirrhosisCommon causeCryptogenic cirrhosisViral hepatitidesAge groupsMulti-institutional retrospective studyYears age group childrenIncidence of cirrhosisCause of cirrhosisFatty liver diseaseDiagnosis of cirrhosisAge group childrenCongenital cholestatic diseasesClinical chartsYounger patientsLiver diseasePathology databaseRetrospective studyCholestatic diseasePathology reportsCirrhosisMetabolic disordersPatientsScant dataYoung adultsClinical utility of genomic analysis in adults with idiopathic liver disease
Hakim A, Zhang X, DeLisle A, Oral EA, Dykas D, Drzewiecki K, Assis DN, Silveira M, Batisti J, Jain D, Bale A, Mistry PK, Vilarinho S. Clinical utility of genomic analysis in adults with idiopathic liver disease. Journal Of Hepatology 2019, 70: 1214-1221. PMID: 31000363, PMCID: PMC6526061, DOI: 10.1016/j.jhep.2019.01.036.Peer-Reviewed Original ResearchConceptsIdiopathic liver diseaseUnexplained liver diseaseManagement of adultsWhole-exome sequencingLiver diseaseAdult patientsUnknown etiologyHeterozygous variantsUse of WESAmelioration of dyslipidemiaDaily insulin requirementLeptin replacement therapyUtility of WESChronic liver diseaseNon-alcoholic steatohepatitisAcademic health care centerHealth care centersHomozygous pathogenic variantUnrelated adult patientsNon-oncological diseasesDisease preventive measuresInsulin requirementsLean patientsDevastating complicationLiver aminotransferases
2018
Antigen-mediated regulation in monoclonal gammopathies and myeloma
Nair S, Sng J, Boddupalli CS, Seckinger A, Chesi M, Fulciniti M, Zhang L, Rauniyar N, Lopez M, Neparidze N, Parker T, Munshi NC, Sexton R, Barlogie B, Orlowski R, Bergsagel L, Hose D, Flavell RA, Mistry PK, Meffre E, Dhodapkar MV. Antigen-mediated regulation in monoclonal gammopathies and myeloma. JCI Insight 2018, 3: e98259. PMID: 29669929, PMCID: PMC5931125, DOI: 10.1172/jci.insight.98259.Peer-Reviewed Original ResearchConceptsMultiple myelomaPlasma cellsGaucher diseaseAntigenic stimulationMonoclonal gammopathyAntigen-driven stimulationMonoclonal IgClonal IgB cell receptorSingle tumor cellsPatient cohortUndetermined significanceVivo responsivenessMalignant cloneGammopathyTumor growthMonoclonal tumorsCell receptorTumor cellsAntigenGene expression profilingStimulationClonal natureMyelomaTumorsHepatocellular carcinoma in Gaucher disease: an international case series
Regenboog M, van Dussen L, Verheij J, Weinreb NJ, Santosa D, vom Dahl S, Häussinger D, Müller MN, Canbay A, Rigoldi M, Piperno A, Dinur T, Zimran A, Mistry PK, Salah KY, Belmatoug N, Kuter DJ, Hollak CEM. Hepatocellular carcinoma in Gaucher disease: an international case series. Journal Of Inherited Metabolic Disease 2018, 41: 819-827. PMID: 29423829, PMCID: PMC6133179, DOI: 10.1007/s10545-018-0142-y.Peer-Reviewed Original ResearchConceptsHepatocellular carcinomaCase seriesGD patientsIron overloadChronic hepatitis C infectionGaucher diseaseDevelopment of HCCLiver-specific complicationsHepatitis C infectionInternational case seriesDifferent referral centersMain risk factorsType 1 patientsGD type 1 patientsGD pathogenesisC infectionPrior splenectomyReferral centerLiver cirrhosisHistopathological examinationTransferrin saturationHCC riskLiver fibrosisRisk factorsHCC development
2017
Glucosylsphingosine Promotes α-Synuclein Pathology in Mutant GBA-Associated Parkinson's Disease
Taguchi YV, Liu J, Ruan J, Pacheco J, Zhang X, Abbasi J, Keutzer J, Mistry PK, Chandra SS. Glucosylsphingosine Promotes α-Synuclein Pathology in Mutant GBA-Associated Parkinson's Disease. Journal Of Neuroscience 2017, 37: 9617-9631. PMID: 28847804, PMCID: PMC5628407, DOI: 10.1523/jneurosci.1525-17.2017.Peer-Reviewed Original ResearchConceptsΑ-synuclein pathologyParkinson's diseaseCommon genetic risk factorGenetic risk factorsGaucher diseaseRisk factorsPD pathologyOligomeric α-synuclein speciesPD mouse brainPathological aggregationΑ-synuclein speciesHuman cellsAttractive therapeutic targetΑ-synuclein aggregationPrevalent neurodegenerative disorderGD patientsFunction mechanismPD riskMouse linesMutantsTherapeutic targetMutationsMouse brainNeurodegenerative disordersDiseaseTransformation in pretreatment manifestations of Gaucher disease type 1 during two decades of alglucerase/imiglucerase enzyme replacement therapy in the International Collaborative Gaucher Group (ICGG) Gaucher Registry
Mistry PK, Batista JL, Andersson HC, Balwani M, Burrow TA, Charrow J, Kaplan P, Khan A, Kishnani PS, Kolodny EH, Rosenbloom B, Scott CR, Weinreb N. Transformation in pretreatment manifestations of Gaucher disease type 1 during two decades of alglucerase/imiglucerase enzyme replacement therapy in the International Collaborative Gaucher Group (ICGG) Gaucher Registry. American Journal Of Hematology 2017, 92: 929-939. PMID: 28569047, PMCID: PMC5600096, DOI: 10.1002/ajh.24801.Peer-Reviewed Original ResearchConceptsImiglucerase enzyme replacement therapyEnzyme replacement therapyNon-splenectomized patientsAge groupsBone crisesERT initiationBone eventsBone manifestationsReplacement therapyLow prevalenceInitiation of ERTIntroduction of ERTInternational Collaborative Gaucher Group Gaucher RegistryGaucher disease type 1Severe clinical manifestationsType 1 patientsDisease type 1Gaucher disease type 1 patientsGD1 patientsSkeletal complicationsCertain age groupsAdult patientsPediatric patientsTreatment initiationGaucher Registry
2016
Validating glycoprotein non-metastatic melanoma B (gpNMB, osteoactivin), a new biomarker of Gaucher disease
Murugesan V, Liu J, Yang R, Lin H, Lischuk A, Pastores G, Zhang X, Chuang WL, Mistry PK. Validating glycoprotein non-metastatic melanoma B (gpNMB, osteoactivin), a new biomarker of Gaucher disease. Blood Cells Molecules And Diseases 2016, 68: 47-53. PMID: 28003098, PMCID: PMC5468511, DOI: 10.1016/j.bcmd.2016.12.002.Peer-Reviewed Original ResearchConceptsGaucher diseaseSerum levelsMelanoma BImiglucerase enzyme replacement therapyCohort of patientsEnzyme replacement therapyOverall disease severityGPNMB levelsDisease activityUntreated patientsReplacement therapyDisease miceDisease progressionIndividual patientsLarge cohortHematological diseasesStriking elevationPatientsNew biomarkersDisease pathophysiologyDisease severityDiseaseOrgan compartmentsBiomarkersDisease mechanismsLong-term hematological, visceral, and growth outcomes in children with Gaucher disease type 3 treated with imiglucerase in the International Collaborative Gaucher Group Gaucher Registry
El-Beshlawy A, Tylki-Szymanska A, Vellodi A, Belmatoug N, Grabowski GA, Kolodny EH, Batista JL, Cox GF, Mistry PK. Long-term hematological, visceral, and growth outcomes in children with Gaucher disease type 3 treated with imiglucerase in the International Collaborative Gaucher Group Gaucher Registry. Molecular Genetics And Metabolism 2016, 120: 47-56. PMID: 28040394, DOI: 10.1016/j.ymgme.2016.12.001.Peer-Reviewed Original ResearchConceptsEnzyme replacement therapyInternational Collaborative Gaucher Group Gaucher RegistryGD3 patientsGaucher RegistryPrimary central nervous system involvementImiglucerase enzyme replacement therapyCentral nervous system involvementGaucher diseaseSingle-center seriesGrowth outcomesNervous system involvementGaucher disease type 3Height z-scoreNumber of patientsLife-prolonging benefitsBroad phenotypic spectrumImiglucerase treatmentVisceral diseaseHemoglobin levelsPlatelet countReplacement therapySevere anemiaVisceral manifestationsSpleen volumeSystem involvementGlucosylsphingosine is a key biomarker of Gaucher disease
Murugesan V, Chuang W, Liu J, Lischuk A, Kacena K, Lin H, Pastores GM, Yang R, Keutzer J, Zhang K, Mistry PK. Glucosylsphingosine is a key biomarker of Gaucher disease. American Journal Of Hematology 2016, 91: 1082-1089. PMID: 27441734, PMCID: PMC5234703, DOI: 10.1002/ajh.24491.Peer-Reviewed Original ResearchConceptsEnzyme replacement therapyLyso-GL1GD type 1Gaucher diseasePropensity scoreUntreated GD patientsWilcoxon Mann-Whitney testAccumulation of glucosylceramideMann-Whitney testTreatment modeImmune dysregulationCCL18 levelsReplacement therapyGD patientsHealthy controlsPropensity scoringPatientsSkeletal diseaseType 1Comparable groupsMarked reductionMultiple linear regressionSignificant predictorsKey biomarkersLinear regression
2015
Effect of Oral Eliglustat on Splenomegaly in Patients With Gaucher Disease Type 1: The ENGAGE Randomized Clinical Trial
Mistry PK, Lukina E, Turkia H, Amato D, Baris H, Dasouki M, Ghosn M, Mehta A, Packman S, Pastores G, Petakov M, Assouline S, Balwani M, Danda S, Hadjiev E, Ortega A, Shankar S, Solano MH, Ross L, Angell J, Peterschmitt MJ. Effect of Oral Eliglustat on Splenomegaly in Patients With Gaucher Disease Type 1: The ENGAGE Randomized Clinical Trial. JAMA 2015, 313: 695-706. PMID: 25688781, PMCID: PMC4962880, DOI: 10.1001/jama.2015.459.Peer-Reviewed Original ResearchConceptsGaucher disease type 1Disease type 1Efficacy end pointSpleen volumeHemoglobin levelsPlatelet countLiver volumeType 1End pointUntreated adultsOral substrate reduction therapyPrimary efficacy end pointSecondary efficacy end pointsOpen-label extension studyPercentage changeAbsolute treatment differenceEffective oral therapyMean spleen volumePlacebo-controlled trialSecondary end pointsSerious adverse eventsEnzyme replacement therapySubstrate reduction therapyBaseline splenomegalyEligible patients
2014
Individual exome analysis in diagnosis and management of paediatric liver failure of indeterminate aetiology
Vilarinho S, Choi M, Jain D, Malhotra A, Kulkarni S, Pashankar D, Phatak U, Patel M, Bale A, Mane S, Lifton RP, Mistry PK. Individual exome analysis in diagnosis and management of paediatric liver failure of indeterminate aetiology. Journal Of Hepatology 2014, 61: 1056-1063. PMID: 25016221, PMCID: PMC4203706, DOI: 10.1016/j.jhep.2014.06.038.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceBase SequenceCarboxylic Ester HydrolasesChildCholestasisDNA Mutational AnalysisEnd Stage Liver DiseaseExomeFatal OutcomeFemaleGenes, RecessiveHepatolenticular DegenerationHeterozygoteHomozygoteHumansInfant, NewbornLiver FailureLiver Failure, AcuteMaleMembrane ProteinsMitochondrial ProteinsMolecular Sequence DataPedigreeReceptor, Notch2RNA Splice SitesSequence Homology, Amino AcidConceptsFatal acute liver failureWhole-exome sequencingAdvanced liver diseaseAcute liver failureIndeterminate etiologyYear old femaleLiver failureLiver diseaseMetabolic liver diseasePatient 3Treatment optionsPhenotypic spectrumPediatric liver failureDecompensated liver cirrhosisManagement of childrenOptimal treatment optionsAge 3 monthsNovel inborn errorLiver transplantAtypical presentationLiver cirrhosisHepatocerebral mitochondrial DNA depletion syndromePatient 1Patient 2Unknown etiology
2013
Calcium Ameliorates Diarrhea in Immunocompromised Children
Cheng SX, Bai HX, Gonzalez‐Peralta R, Mistry PK, Gorelick FS. Calcium Ameliorates Diarrhea in Immunocompromised Children. Journal Of Pediatric Gastroenterology And Nutrition 2013, 56: 641-644. PMID: 23343935, PMCID: PMC4448079, DOI: 10.1097/mpg.0b013e3182868946.Peer-Reviewed Original ResearchMutations in GBA2 Cause Autosomal-Recessive Cerebellar Ataxia with Spasticity
Hammer MB, Eleuch-Fayache G, Schottlaender LV, Nehdi H, Gibbs JR, Arepalli SK, Chong SB, Hernandez DG, Sailer A, Liu G, Mistry PK, Cai H, Shrader G, Sassi C, Bouhlal Y, Houlden H, Hentati F, Amouri R, Singleton AB. Mutations in GBA2 Cause Autosomal-Recessive Cerebellar Ataxia with Spasticity. American Journal Of Human Genetics 2013, 92: 245-251. PMID: 23332917, PMCID: PMC3567281, DOI: 10.1016/j.ajhg.2012.12.012.Peer-Reviewed Original ResearchRare disease clinical research network's urea cycle consortium delivers a successful clinical trial to improve alternate pathway therapy
Mistry PK. Rare disease clinical research network's urea cycle consortium delivers a successful clinical trial to improve alternate pathway therapy. Hepatology 2013, 57: 2100-2102. PMID: 23080135, DOI: 10.1002/hep.26106.Peer-Reviewed Original Research