I RISULTATI A LUNGO TERMINE DELLA ERT NELLE FORME GIOVANILI

E ADULTE DELLA GLICOGENOSI 2

Bruno Bembi

Centro di Coordinamento Regionaleper le Malattie Rare

AOUD S Maria della Misericordia di Udine

25 novembre 2014

Glicogenosis II malattia di Pompe o deficit di maltasi acida

bull Malattia da accumulo lisosomiale

bull ereditarietagrave autosomico recessiva

bull Deficit dellrsquoa-glucosidasi lisosomiale

bull accumulo di glicogeno nei lisosomi deimuscoli scheletrici lisci e del miocardio

Glicogenosi IIcontinuum fenotipico

bullDebolezza muscolare progressiva

bullCardiomegalia and cardiomiopatia

bullEpatomegalia moderata

bullMacroglossia

bullDifficoltagrave drsquoalimentazione

bullInfezioni respiratorie frequenti

bullDistress respiratorio

bullRitardo tappe motorie

bullCK elevate (marcatamente)

bullDecorso progressivo rapido fatale

bullno attivitagrave residua della GAA

bullDebolezza muscolare progressiva

bullNo cariomiopatia

bullEpatomegalia moderata

bullDifficltagrave deglutizione

bullInfezioni respiratorie frequenti

bullDistress respiratorio

bullFaticabilitagrave muscolare

bullCK elevate

bullattivitagrave residua della GAA

Esordio infantile Forme tardive

Basta sulla dimostrazione del deficit di GAA (linfociti fibroblasti amniociti)

Possibile misurare lrsquoattivitagrave enzimatica sugoccia di sangue su carta da filtro (screening)

Altri parametri di laboratorio CK LDH AST ALT oligosacharides su urine e plasma

Conferma diagnostica analisi molecolare

Diagnosi di Laboratorio

Allele frequency in the Italian infantile GSDII population

c525delT(118)

c1064TgtC(79)

c1655TgtC(105)

c-32-13TgtG(423)

c2237GgtA(103)

Allele frequency in the Italian late onset GSDII population

Approcci Terapeutici

bull Terapie di Supporto

bull Dieta + fisioterapia

bull Terapia Enzimatica Sostitutiva

Terapia Enzimatica Sostitutiva

Myozyme 20 mgkgevery two weeks

Durata 36 months

Long-term observational non-randomized study of enzyme

replacement therapy in late-onset glycogenosis type IIBembi B1 Pisa FE Confalonieri M Ciana G Fiumara A Parini R Rigoldi M

Moglia A Costa A Carlucci A Danesino C Pittis MG Dardis A Ravaglia S

J Inherit Metab Dis 2010 Dec33(6)727-3

Studio multicentrico (5 centers) con il supporto dellrsquoAgenziaItaliana del Farmaco (AIFA)

Patienti

Giovanili 7 (5 maschi 2 femmine etagrave 8-18 yrs)

bullAdulti 22 (11 maschi 11 femmine etagrave 29-83)

6 pazienti adultsi esclusi dallo studio per 2 HCV 1 HIV 1 leyucopenia idiopatica 1 cancro sel seno 1 etagrave avanzata)

Glicogenosis II malattia di Pompe o deficit di maltasi acida

bull Malattia da accumulo lisosomiale

bull ereditarietagrave autosomico recessiva

bull Deficit dellrsquoa-glucosidasi lisosomiale

bull accumulo di glicogeno nei lisosomi deimuscoli scheletrici lisci e del miocardio

Glicogenosi IIcontinuum fenotipico

bullDebolezza muscolare progressiva

bullCardiomegalia and cardiomiopatia

bullEpatomegalia moderata

bullMacroglossia

bullDifficoltagrave drsquoalimentazione

bullInfezioni respiratorie frequenti

bullDistress respiratorio

bullRitardo tappe motorie

bullCK elevate (marcatamente)

bullDecorso progressivo rapido fatale

bullno attivitagrave residua della GAA

bullDebolezza muscolare progressiva

bullNo cariomiopatia

bullEpatomegalia moderata

bullDifficltagrave deglutizione

bullInfezioni respiratorie frequenti

bullDistress respiratorio

bullFaticabilitagrave muscolare

bullCK elevate

bullattivitagrave residua della GAA

Esordio infantile Forme tardive

Basta sulla dimostrazione del deficit di GAA (linfociti fibroblasti amniociti)

Possibile misurare lrsquoattivitagrave enzimatica sugoccia di sangue su carta da filtro (screening)

Altri parametri di laboratorio CK LDH AST ALT oligosacharides su urine e plasma

Conferma diagnostica analisi molecolare

Diagnosi di Laboratorio

Allele frequency in the Italian infantile GSDII population

c525delT(118)

c1064TgtC(79)

c1655TgtC(105)

c-32-13TgtG(423)

c2237GgtA(103)

Allele frequency in the Italian late onset GSDII population

Approcci Terapeutici

bull Terapie di Supporto

bull Dieta + fisioterapia

bull Terapia Enzimatica Sostitutiva

Terapia Enzimatica Sostitutiva

Myozyme 20 mgkgevery two weeks

Durata 36 months

Long-term observational non-randomized study of enzyme

replacement therapy in late-onset glycogenosis type IIBembi B1 Pisa FE Confalonieri M Ciana G Fiumara A Parini R Rigoldi M

Moglia A Costa A Carlucci A Danesino C Pittis MG Dardis A Ravaglia S

J Inherit Metab Dis 2010 Dec33(6)727-3

Studio multicentrico (5 centers) con il supporto dellrsquoAgenziaItaliana del Farmaco (AIFA)

Patienti

Giovanili 7 (5 maschi 2 femmine etagrave 8-18 yrs)

bullAdulti 22 (11 maschi 11 femmine etagrave 29-83)

6 pazienti adultsi esclusi dallo studio per 2 HCV 1 HIV 1 leyucopenia idiopatica 1 cancro sel seno 1 etagrave avanzata)

Glicogenosi IIcontinuum fenotipico

bullDebolezza muscolare progressiva

bullCardiomegalia and cardiomiopatia

bullEpatomegalia moderata

bullMacroglossia

bullDifficoltagrave drsquoalimentazione

bullInfezioni respiratorie frequenti

bullDistress respiratorio

bullRitardo tappe motorie

bullCK elevate (marcatamente)

bullDecorso progressivo rapido fatale

bullno attivitagrave residua della GAA

bullDebolezza muscolare progressiva

bullNo cariomiopatia

bullEpatomegalia moderata

bullDifficltagrave deglutizione

bullInfezioni respiratorie frequenti

bullDistress respiratorio

bullFaticabilitagrave muscolare

bullCK elevate

bullattivitagrave residua della GAA

Esordio infantile Forme tardive

Basta sulla dimostrazione del deficit di GAA (linfociti fibroblasti amniociti)

Possibile misurare lrsquoattivitagrave enzimatica sugoccia di sangue su carta da filtro (screening)

Altri parametri di laboratorio CK LDH AST ALT oligosacharides su urine e plasma

Conferma diagnostica analisi molecolare

Diagnosi di Laboratorio

Allele frequency in the Italian infantile GSDII population

c525delT(118)

c1064TgtC(79)

c1655TgtC(105)

c-32-13TgtG(423)

c2237GgtA(103)

Allele frequency in the Italian late onset GSDII population

Approcci Terapeutici

bull Terapie di Supporto

bull Dieta + fisioterapia

bull Terapia Enzimatica Sostitutiva

Terapia Enzimatica Sostitutiva

Myozyme 20 mgkgevery two weeks

Durata 36 months

Long-term observational non-randomized study of enzyme

replacement therapy in late-onset glycogenosis type IIBembi B1 Pisa FE Confalonieri M Ciana G Fiumara A Parini R Rigoldi M

Moglia A Costa A Carlucci A Danesino C Pittis MG Dardis A Ravaglia S

J Inherit Metab Dis 2010 Dec33(6)727-3

Studio multicentrico (5 centers) con il supporto dellrsquoAgenziaItaliana del Farmaco (AIFA)

Patienti

Giovanili 7 (5 maschi 2 femmine etagrave 8-18 yrs)

bullAdulti 22 (11 maschi 11 femmine etagrave 29-83)

6 pazienti adultsi esclusi dallo studio per 2 HCV 1 HIV 1 leyucopenia idiopatica 1 cancro sel seno 1 etagrave avanzata)

Basta sulla dimostrazione del deficit di GAA (linfociti fibroblasti amniociti)

Possibile misurare lrsquoattivitagrave enzimatica sugoccia di sangue su carta da filtro (screening)

Altri parametri di laboratorio CK LDH AST ALT oligosacharides su urine e plasma

Conferma diagnostica analisi molecolare

Diagnosi di Laboratorio

Allele frequency in the Italian infantile GSDII population

c525delT(118)

c1064TgtC(79)

c1655TgtC(105)

c-32-13TgtG(423)

c2237GgtA(103)

Allele frequency in the Italian late onset GSDII population

Approcci Terapeutici

bull Terapie di Supporto

bull Dieta + fisioterapia

bull Terapia Enzimatica Sostitutiva

Terapia Enzimatica Sostitutiva

Myozyme 20 mgkgevery two weeks

Durata 36 months

Long-term observational non-randomized study of enzyme

replacement therapy in late-onset glycogenosis type IIBembi B1 Pisa FE Confalonieri M Ciana G Fiumara A Parini R Rigoldi M

Moglia A Costa A Carlucci A Danesino C Pittis MG Dardis A Ravaglia S

J Inherit Metab Dis 2010 Dec33(6)727-3

Studio multicentrico (5 centers) con il supporto dellrsquoAgenziaItaliana del Farmaco (AIFA)

Patienti

Giovanili 7 (5 maschi 2 femmine etagrave 8-18 yrs)

bullAdulti 22 (11 maschi 11 femmine etagrave 29-83)

6 pazienti adultsi esclusi dallo studio per 2 HCV 1 HIV 1 leyucopenia idiopatica 1 cancro sel seno 1 etagrave avanzata)

Allele frequency in the Italian infantile GSDII population

c525delT(118)

c1064TgtC(79)

c1655TgtC(105)

c-32-13TgtG(423)

c2237GgtA(103)

Allele frequency in the Italian late onset GSDII population

Approcci Terapeutici

bull Terapie di Supporto

bull Dieta + fisioterapia

bull Terapia Enzimatica Sostitutiva

Terapia Enzimatica Sostitutiva

Myozyme 20 mgkgevery two weeks

Durata 36 months

Long-term observational non-randomized study of enzyme

replacement therapy in late-onset glycogenosis type IIBembi B1 Pisa FE Confalonieri M Ciana G Fiumara A Parini R Rigoldi M

Moglia A Costa A Carlucci A Danesino C Pittis MG Dardis A Ravaglia S

J Inherit Metab Dis 2010 Dec33(6)727-3

Studio multicentrico (5 centers) con il supporto dellrsquoAgenziaItaliana del Farmaco (AIFA)

Patienti

Giovanili 7 (5 maschi 2 femmine etagrave 8-18 yrs)

bullAdulti 22 (11 maschi 11 femmine etagrave 29-83)

6 pazienti adultsi esclusi dallo studio per 2 HCV 1 HIV 1 leyucopenia idiopatica 1 cancro sel seno 1 etagrave avanzata)

c-32-13TgtG(423)

c2237GgtA(103)

Allele frequency in the Italian late onset GSDII population

Approcci Terapeutici

bull Terapie di Supporto

bull Dieta + fisioterapia

bull Terapia Enzimatica Sostitutiva

Terapia Enzimatica Sostitutiva

Myozyme 20 mgkgevery two weeks

Durata 36 months

Long-term observational non-randomized study of enzyme

replacement therapy in late-onset glycogenosis type IIBembi B1 Pisa FE Confalonieri M Ciana G Fiumara A Parini R Rigoldi M

Moglia A Costa A Carlucci A Danesino C Pittis MG Dardis A Ravaglia S

J Inherit Metab Dis 2010 Dec33(6)727-3

Studio multicentrico (5 centers) con il supporto dellrsquoAgenziaItaliana del Farmaco (AIFA)

Patienti

Giovanili 7 (5 maschi 2 femmine etagrave 8-18 yrs)

bullAdulti 22 (11 maschi 11 femmine etagrave 29-83)

6 pazienti adultsi esclusi dallo studio per 2 HCV 1 HIV 1 leyucopenia idiopatica 1 cancro sel seno 1 etagrave avanzata)

Approcci Terapeutici

bull Terapie di Supporto

bull Dieta + fisioterapia

bull Terapia Enzimatica Sostitutiva

Terapia Enzimatica Sostitutiva

Myozyme 20 mgkgevery two weeks

Durata 36 months

Long-term observational non-randomized study of enzyme

replacement therapy in late-onset glycogenosis type IIBembi B1 Pisa FE Confalonieri M Ciana G Fiumara A Parini R Rigoldi M

Moglia A Costa A Carlucci A Danesino C Pittis MG Dardis A Ravaglia S

J Inherit Metab Dis 2010 Dec33(6)727-3

Studio multicentrico (5 centers) con il supporto dellrsquoAgenziaItaliana del Farmaco (AIFA)

Patienti

Giovanili 7 (5 maschi 2 femmine etagrave 8-18 yrs)

bullAdulti 22 (11 maschi 11 femmine etagrave 29-83)

6 pazienti adultsi esclusi dallo studio per 2 HCV 1 HIV 1 leyucopenia idiopatica 1 cancro sel seno 1 etagrave avanzata)

Terapia Enzimatica Sostitutiva

Myozyme 20 mgkgevery two weeks

Durata 36 months

Long-term observational non-randomized study of enzyme

replacement therapy in late-onset glycogenosis type IIBembi B1 Pisa FE Confalonieri M Ciana G Fiumara A Parini R Rigoldi M

Moglia A Costa A Carlucci A Danesino C Pittis MG Dardis A Ravaglia S

J Inherit Metab Dis 2010 Dec33(6)727-3

Studio multicentrico (5 centers) con il supporto dellrsquoAgenziaItaliana del Farmaco (AIFA)

Patienti

Giovanili 7 (5 maschi 2 femmine etagrave 8-18 yrs)

bullAdulti 22 (11 maschi 11 femmine etagrave 29-83)

6 pazienti adultsi esclusi dallo studio per 2 HCV 1 HIV 1 leyucopenia idiopatica 1 cancro sel seno 1 etagrave avanzata)

Myozyme 20 mgkgevery two weeks

Durata 36 months

Long-term observational non-randomized study of enzyme

replacement therapy in late-onset glycogenosis type IIBembi B1 Pisa FE Confalonieri M Ciana G Fiumara A Parini R Rigoldi M

Moglia A Costa A Carlucci A Danesino C Pittis MG Dardis A Ravaglia S

J Inherit Metab Dis 2010 Dec33(6)727-3

Studio multicentrico (5 centers) con il supporto dellrsquoAgenziaItaliana del Farmaco (AIFA)

Patienti

Giovanili 7 (5 maschi 2 femmine etagrave 8-18 yrs)

bullAdulti 22 (11 maschi 11 femmine etagrave 29-83)

6 pazienti adultsi esclusi dallo studio per 2 HCV 1 HIV 1 leyucopenia idiopatica 1 cancro sel seno 1 etagrave avanzata)

Giovanili7 (304)

Adulti16 (696)

Etagrave (minndashmax) 8 - 18 29 ndash 62

Etagrave (mean + SD) 139 plusmn 37 526 plusmn 28

Femmine (n) 2 286 7 437

Maschi (n) 5 714 9 563

Etagrave primi sintomi (media+SD) 25 plusmn 13 257 128

Etagrave diagnosi (mdia+SD) 28 plusmn 14 334 plusmn 146

Etagrave TES (media+SD) 120 plusmn 33 471 plusmn 107

BMI (media+SD) 180 plusmn 64 223 plusmn 49

Tracheostomia (n) 1 143 3 187

Support Ventilatorio mascherina(n)

2 143 11 687

6MWT completato (n)2 286 8 500

6MWT non completato (n) 5 714 8 500

Dati Demografici e caratteristiche cliniche alla baseline

Protocol di studio

bull Visite di Follow-up ogni 3 mesi per i primi 24 months poi ogni 6

bull Functione Muscolare Scala di Walton 6MWT

bull Functione Respiratoria supporto ventilatorio CV FEV1 pCO2 arteriosa

bull Sintomi Clinici (cefalea dolore muscolare)

bull Parametri biochimici enzimi muscolari

WOLTON SCALEaccording to Slonime et al (Muscle Nerve 35 70-77 2007)

Grade

0 All activities normal

1 Walks normal unable to run freely

2 Defect in posturegait

25 Sometimes use of bannister to climb stairs

3 Stairs only with bannister

35 Sometimes unable to climb stairs with bannister

4 Walks without assistance unable to climb stairs

5 Walks without assistance unable to rise from a chair

6 Walks only with calipers or other aids

7 Wheelchair bound

WS score T0 T6 T12 T18 T24 P

T0-T12

p

T0-T24

0 - 28

348

9

391

10

435

11

478

12

522

00033 0000225 - 5

9

304

7

304

8

348

7

304

7

304

6 ndash 7 8

348

7

304

5

217

5

217

4

174

6MWT T0 T6 T12 T24 T36P

T0-T12P

T0-T24

Overall

median (m)ndeg pts

197023

360223

3813 23

331021

328021

lt00001 lt00001

Juveniles

Median (m)ndeg pts

57297

62607

58907

72005

63005

lt00001 00002

Adults

Median (m)ndeg pts

116616

203016

213116

200016

206-016

lt00001 00002

T0 T6 T12 T24 T36P

T0-T12P

T0-T24

Pts withventilatorysupport

13 11 11 11 11

Hoursday 14 12 8 8 8

pCO2 (mmHg)

440 400 404 44-0 40-8 01127 00189

median

SI NO P

cefalea

T0 8 276 21 72400122

T12 2 69 27 931

Dolore muscolare

T0 11 379 18 62100020

T12 3 103 26 897

Risposta del dolore alla TES (29 pazienti 7 ppediatrici 22 adulti)

T 0 T 36

DEXA

Osteoporosi 1 (Z score -4) 1

Normali 8 (Z score -02 ndash 01) 8

Scoliosi Severa 1

Moderata 2

Lieve 4

Normali 2

Iperlordosi Severa 1

Moderata 4

Deambulazione alterata 3

BMD

Bembi et al Unpublished data

Enzyme replacement therapy in juvenile glycogenosis

type II a longitudinal studyLaura Deroma Mattia Guerra Annalisa Sechi Giovanni Ciana

Giorgia Cisilino Andrea Dardis Bruno Bembi

European Journal of PediatricsJune 2014 Volume 173 Issue 6 pp 805-813

Protocol di studio

bull Visite di Follow-up ogni 3 mesi per i primi 24 months poi ogni 6

bull Functione Muscolare Scala di Walton 6MWT

bull Functione Respiratoria supporto ventilatorio CV FEV1 pCO2 arteriosa

bull Sintomi Clinici (cefalea dolore muscolare)

bull Parametri biochimici enzimi muscolari

WOLTON SCALEaccording to Slonime et al (Muscle Nerve 35 70-77 2007)

Grade

0 All activities normal

1 Walks normal unable to run freely

2 Defect in posturegait

25 Sometimes use of bannister to climb stairs

3 Stairs only with bannister

35 Sometimes unable to climb stairs with bannister

4 Walks without assistance unable to climb stairs

5 Walks without assistance unable to rise from a chair

6 Walks only with calipers or other aids

7 Wheelchair bound

WS score T0 T6 T12 T18 T24 P

T0-T12

p

T0-T24

0 - 28

348

9

391

10

435

11

478

12

522

00033 0000225 - 5

9

304

7

304

8

348

7

304

7

304

6 ndash 7 8

348

7

304

5

217

5

217

4

174

6MWT T0 T6 T12 T24 T36P

T0-T12P

T0-T24

Overall

median (m)ndeg pts

197023

360223

3813 23

331021

328021

lt00001 lt00001

Juveniles

Median (m)ndeg pts

57297

62607

58907

72005

63005

lt00001 00002

Adults

Median (m)ndeg pts

116616

203016

213116

200016

206-016

lt00001 00002

T0 T6 T12 T24 T36P

T0-T12P

T0-T24

Pts withventilatorysupport

13 11 11 11 11

Hoursday 14 12 8 8 8

pCO2 (mmHg)

440 400 404 44-0 40-8 01127 00189

median

SI NO P

cefalea

T0 8 276 21 72400122

T12 2 69 27 931

Dolore muscolare

T0 11 379 18 62100020

T12 3 103 26 897

Risposta del dolore alla TES (29 pazienti 7 ppediatrici 22 adulti)

T 0 T 36

DEXA

Osteoporosi 1 (Z score -4) 1

Normali 8 (Z score -02 ndash 01) 8

Scoliosi Severa 1

Moderata 2

Lieve 4

Normali 2

Iperlordosi Severa 1

Moderata 4

Deambulazione alterata 3

BMD

Bembi et al Unpublished data

Enzyme replacement therapy in juvenile glycogenosis

type II a longitudinal studyLaura Deroma Mattia Guerra Annalisa Sechi Giovanni Ciana

Giorgia Cisilino Andrea Dardis Bruno Bembi

European Journal of PediatricsJune 2014 Volume 173 Issue 6 pp 805-813

WOLTON SCALEaccording to Slonime et al (Muscle Nerve 35 70-77 2007)

Grade

0 All activities normal

1 Walks normal unable to run freely

2 Defect in posturegait

25 Sometimes use of bannister to climb stairs

3 Stairs only with bannister

35 Sometimes unable to climb stairs with bannister

4 Walks without assistance unable to climb stairs

5 Walks without assistance unable to rise from a chair

6 Walks only with calipers or other aids

7 Wheelchair bound

WS score T0 T6 T12 T18 T24 P

T0-T12

p

T0-T24

0 - 28

348

9

391

10

435

11

478

12

522

00033 0000225 - 5

9

304

7

304

8

348

7

304

7

304

6 ndash 7 8

348

7

304

5

217

5

217

4

174

6MWT T0 T6 T12 T24 T36P

T0-T12P

T0-T24

Overall

median (m)ndeg pts

197023

360223

3813 23

331021

328021

lt00001 lt00001

Juveniles

Median (m)ndeg pts

57297

62607

58907

72005

63005

lt00001 00002

Adults

Median (m)ndeg pts

116616

203016

213116

200016

206-016

lt00001 00002

T0 T6 T12 T24 T36P

T0-T12P

T0-T24

Pts withventilatorysupport

13 11 11 11 11

Hoursday 14 12 8 8 8

pCO2 (mmHg)

440 400 404 44-0 40-8 01127 00189

median

SI NO P

cefalea

T0 8 276 21 72400122

T12 2 69 27 931

Dolore muscolare

T0 11 379 18 62100020

T12 3 103 26 897

Risposta del dolore alla TES (29 pazienti 7 ppediatrici 22 adulti)

T 0 T 36

DEXA

Osteoporosi 1 (Z score -4) 1

Normali 8 (Z score -02 ndash 01) 8

Scoliosi Severa 1

Moderata 2

Lieve 4

Normali 2

Iperlordosi Severa 1

Moderata 4

Deambulazione alterata 3

BMD

Bembi et al Unpublished data

Enzyme replacement therapy in juvenile glycogenosis

type II a longitudinal studyLaura Deroma Mattia Guerra Annalisa Sechi Giovanni Ciana

Giorgia Cisilino Andrea Dardis Bruno Bembi

European Journal of PediatricsJune 2014 Volume 173 Issue 6 pp 805-813

WS score T0 T6 T12 T18 T24 P

T0-T12

p

T0-T24

0 - 28

348

9

391

10

435

11

478

12

522

00033 0000225 - 5

9

304

7

304

8

348

7

304

7

304

6 ndash 7 8

348

7

304

5

217

5

217

4

174

6MWT T0 T6 T12 T24 T36P

T0-T12P

T0-T24

Overall

median (m)ndeg pts

197023

360223

3813 23

331021

328021

lt00001 lt00001

Juveniles

Median (m)ndeg pts

57297

62607

58907

72005

63005

lt00001 00002

Adults

Median (m)ndeg pts

116616

203016

213116

200016

206-016

lt00001 00002

T0 T6 T12 T24 T36P

T0-T12P

T0-T24

Pts withventilatorysupport

13 11 11 11 11

Hoursday 14 12 8 8 8

pCO2 (mmHg)

440 400 404 44-0 40-8 01127 00189

median

SI NO P

cefalea

T0 8 276 21 72400122

T12 2 69 27 931

Dolore muscolare

T0 11 379 18 62100020

T12 3 103 26 897

Risposta del dolore alla TES (29 pazienti 7 ppediatrici 22 adulti)

T 0 T 36

DEXA

Osteoporosi 1 (Z score -4) 1

Normali 8 (Z score -02 ndash 01) 8

Scoliosi Severa 1

Moderata 2

Lieve 4

Normali 2

Iperlordosi Severa 1

Moderata 4

Deambulazione alterata 3

BMD

Bembi et al Unpublished data

Enzyme replacement therapy in juvenile glycogenosis

type II a longitudinal studyLaura Deroma Mattia Guerra Annalisa Sechi Giovanni Ciana

Giorgia Cisilino Andrea Dardis Bruno Bembi

European Journal of PediatricsJune 2014 Volume 173 Issue 6 pp 805-813

6MWT T0 T6 T12 T24 T36P

T0-T12P

T0-T24

Overall

median (m)ndeg pts

197023

360223

3813 23

331021

328021

lt00001 lt00001

Juveniles

Median (m)ndeg pts

57297

62607

58907

72005

63005

lt00001 00002

Adults

Median (m)ndeg pts

116616

203016

213116

200016

206-016

lt00001 00002

T0 T6 T12 T24 T36P

T0-T12P

T0-T24

Pts withventilatorysupport

13 11 11 11 11

Hoursday 14 12 8 8 8

pCO2 (mmHg)

440 400 404 44-0 40-8 01127 00189

median

SI NO P

cefalea

T0 8 276 21 72400122

T12 2 69 27 931

Dolore muscolare

T0 11 379 18 62100020

T12 3 103 26 897

Risposta del dolore alla TES (29 pazienti 7 ppediatrici 22 adulti)

T 0 T 36

DEXA

Osteoporosi 1 (Z score -4) 1

Normali 8 (Z score -02 ndash 01) 8

Scoliosi Severa 1

Moderata 2

Lieve 4

Normali 2

Iperlordosi Severa 1

Moderata 4

Deambulazione alterata 3

BMD

Bembi et al Unpublished data

Enzyme replacement therapy in juvenile glycogenosis

type II a longitudinal studyLaura Deroma Mattia Guerra Annalisa Sechi Giovanni Ciana

Giorgia Cisilino Andrea Dardis Bruno Bembi

European Journal of PediatricsJune 2014 Volume 173 Issue 6 pp 805-813

T0 T6 T12 T24 T36P

T0-T12P

T0-T24

Pts withventilatorysupport

13 11 11 11 11

Hoursday 14 12 8 8 8

pCO2 (mmHg)

440 400 404 44-0 40-8 01127 00189

median

SI NO P

cefalea

T0 8 276 21 72400122

T12 2 69 27 931

Dolore muscolare

T0 11 379 18 62100020

T12 3 103 26 897

Risposta del dolore alla TES (29 pazienti 7 ppediatrici 22 adulti)

T 0 T 36

DEXA

Osteoporosi 1 (Z score -4) 1

Normali 8 (Z score -02 ndash 01) 8

Scoliosi Severa 1

Moderata 2

Lieve 4

Normali 2

Iperlordosi Severa 1

Moderata 4

Deambulazione alterata 3

BMD

Bembi et al Unpublished data

Enzyme replacement therapy in juvenile glycogenosis

type II a longitudinal studyLaura Deroma Mattia Guerra Annalisa Sechi Giovanni Ciana

Giorgia Cisilino Andrea Dardis Bruno Bembi

European Journal of PediatricsJune 2014 Volume 173 Issue 6 pp 805-813

SI NO P

cefalea

T0 8 276 21 72400122

T12 2 69 27 931

Dolore muscolare

T0 11 379 18 62100020

T12 3 103 26 897

Risposta del dolore alla TES (29 pazienti 7 ppediatrici 22 adulti)

T 0 T 36

DEXA

Osteoporosi 1 (Z score -4) 1

Normali 8 (Z score -02 ndash 01) 8

Scoliosi Severa 1

Moderata 2

Lieve 4

Normali 2

Iperlordosi Severa 1

Moderata 4

Deambulazione alterata 3

BMD

Bembi et al Unpublished data

Enzyme replacement therapy in juvenile glycogenosis

type II a longitudinal studyLaura Deroma Mattia Guerra Annalisa Sechi Giovanni Ciana

Giorgia Cisilino Andrea Dardis Bruno Bembi

European Journal of PediatricsJune 2014 Volume 173 Issue 6 pp 805-813

T 0 T 36

DEXA

Osteoporosi 1 (Z score -4) 1

Normali 8 (Z score -02 ndash 01) 8

Scoliosi Severa 1

Moderata 2

Lieve 4

Normali 2

Iperlordosi Severa 1

Moderata 4

Deambulazione alterata 3

BMD

Bembi et al Unpublished data

Enzyme replacement therapy in juvenile glycogenosis

type II a longitudinal studyLaura Deroma Mattia Guerra Annalisa Sechi Giovanni Ciana

Giorgia Cisilino Andrea Dardis Bruno Bembi

European Journal of PediatricsJune 2014 Volume 173 Issue 6 pp 805-813

Enzyme replacement therapy in juvenile glycogenosis

type II a longitudinal studyLaura Deroma Mattia Guerra Annalisa Sechi Giovanni Ciana

Giorgia Cisilino Andrea Dardis Bruno Bembi

European Journal of PediatricsJune 2014 Volume 173 Issue 6 pp 805-813

Characteristics of the study patients at therapy start (12)

CK creatine kinase

Characteristics of the study patients at therapy start (22)

a Invasive ventilation

Muscle enzymes levels from baseline (therapy start) to the end of follow-up CK creatine phosphokinase LDH lactate dehydrogenase AST aspartate phosphatase ALT alanine aminotransferase

Six-minute walk test (6MWT) Z score frombaseline (therapy start) to the end of follow-up

Forced vital capacity (FVC) from baseline(therapy start) to the end of follow-up FVC values are expressed as percentage pradictedfor height age and gender using standard reference values

New motor outcome function measures in evaluation of late-onset

Pompe disease before and after enzyme replacement therapyAngelini C1 Semplicini C Ravaglia S Moggio M Comi GP Musumeci O Pegoraro E Tonin

P Filosto M Servidei S Morandi L Crescimanno G Marrosu G Siciliano G Mongini T

Toscano A Italian Group on GSDII

Muscle Nerve 2012 Jun45(6)831-4

RESULTS

At baseline the GSGC (Gait Stairs Gower Chair) score correlated with both WGM (P lt

0001 n = 33) and 6MWT (P lt 0001 n = 26) After 1 year of ERT we observed a significant

change in gait stairs and chair performance on the GSGC scale The 6MWT significantly

increased from 319 to 371 meters in 32 patients and the WGM score was reduced

CONCLUSIONS

GSGC is a group of functional tests that requires only a few minutes to perform therefore this

score might be a good indicator to be used in future studies

Characteristics of the study patients at therapy start (22)

a Invasive ventilation

Muscle enzymes levels from baseline (therapy start) to the end of follow-up CK creatine phosphokinase LDH lactate dehydrogenase AST aspartate phosphatase ALT alanine aminotransferase

Six-minute walk test (6MWT) Z score frombaseline (therapy start) to the end of follow-up

Forced vital capacity (FVC) from baseline(therapy start) to the end of follow-up FVC values are expressed as percentage pradictedfor height age and gender using standard reference values

New motor outcome function measures in evaluation of late-onset

Pompe disease before and after enzyme replacement therapyAngelini C1 Semplicini C Ravaglia S Moggio M Comi GP Musumeci O Pegoraro E Tonin

P Filosto M Servidei S Morandi L Crescimanno G Marrosu G Siciliano G Mongini T

Toscano A Italian Group on GSDII

Muscle Nerve 2012 Jun45(6)831-4

RESULTS

At baseline the GSGC (Gait Stairs Gower Chair) score correlated with both WGM (P lt

0001 n = 33) and 6MWT (P lt 0001 n = 26) After 1 year of ERT we observed a significant

change in gait stairs and chair performance on the GSGC scale The 6MWT significantly

increased from 319 to 371 meters in 32 patients and the WGM score was reduced

CONCLUSIONS

GSGC is a group of functional tests that requires only a few minutes to perform therefore this

score might be a good indicator to be used in future studies

Muscle enzymes levels from baseline (therapy start) to the end of follow-up CK creatine phosphokinase LDH lactate dehydrogenase AST aspartate phosphatase ALT alanine aminotransferase

Six-minute walk test (6MWT) Z score frombaseline (therapy start) to the end of follow-up

Forced vital capacity (FVC) from baseline(therapy start) to the end of follow-up FVC values are expressed as percentage pradictedfor height age and gender using standard reference values

New motor outcome function measures in evaluation of late-onset

Pompe disease before and after enzyme replacement therapyAngelini C1 Semplicini C Ravaglia S Moggio M Comi GP Musumeci O Pegoraro E Tonin

P Filosto M Servidei S Morandi L Crescimanno G Marrosu G Siciliano G Mongini T

Toscano A Italian Group on GSDII

Muscle Nerve 2012 Jun45(6)831-4

RESULTS

At baseline the GSGC (Gait Stairs Gower Chair) score correlated with both WGM (P lt

0001 n = 33) and 6MWT (P lt 0001 n = 26) After 1 year of ERT we observed a significant

change in gait stairs and chair performance on the GSGC scale The 6MWT significantly

increased from 319 to 371 meters in 32 patients and the WGM score was reduced

CONCLUSIONS

GSGC is a group of functional tests that requires only a few minutes to perform therefore this

score might be a good indicator to be used in future studies

Six-minute walk test (6MWT) Z score frombaseline (therapy start) to the end of follow-up

Forced vital capacity (FVC) from baseline(therapy start) to the end of follow-up FVC values are expressed as percentage pradictedfor height age and gender using standard reference values

New motor outcome function measures in evaluation of late-onset

Pompe disease before and after enzyme replacement therapyAngelini C1 Semplicini C Ravaglia S Moggio M Comi GP Musumeci O Pegoraro E Tonin

P Filosto M Servidei S Morandi L Crescimanno G Marrosu G Siciliano G Mongini T

Toscano A Italian Group on GSDII

Muscle Nerve 2012 Jun45(6)831-4

RESULTS

At baseline the GSGC (Gait Stairs Gower Chair) score correlated with both WGM (P lt

0001 n = 33) and 6MWT (P lt 0001 n = 26) After 1 year of ERT we observed a significant

change in gait stairs and chair performance on the GSGC scale The 6MWT significantly

increased from 319 to 371 meters in 32 patients and the WGM score was reduced

CONCLUSIONS

GSGC is a group of functional tests that requires only a few minutes to perform therefore this

score might be a good indicator to be used in future studies

New motor outcome function measures in evaluation of late-onset

Pompe disease before and after enzyme replacement therapyAngelini C1 Semplicini C Ravaglia S Moggio M Comi GP Musumeci O Pegoraro E Tonin

P Filosto M Servidei S Morandi L Crescimanno G Marrosu G Siciliano G Mongini T

Toscano A Italian Group on GSDII

Muscle Nerve 2012 Jun45(6)831-4

RESULTS

At baseline the GSGC (Gait Stairs Gower Chair) score correlated with both WGM (P lt

0001 n = 33) and 6MWT (P lt 0001 n = 26) After 1 year of ERT we observed a significant

change in gait stairs and chair performance on the GSGC scale The 6MWT significantly

increased from 319 to 371 meters in 32 patients and the WGM score was reduced

CONCLUSIONS

GSGC is a group of functional tests that requires only a few minutes to perform therefore this

score might be a good indicator to be used in future studies

Observational clinical study in juvenile-adult glycogenosis type

2 patients undergoing enzyme replacement therapy for up to 4

yearsAngelini C1 Semplicini C Ravaglia S Bembi B Servidei S Pegoraro E Moggio M

Filosto M Sette E Crescimanno G Tonin P Parini R Morandi L Marrosu G Greco G

Musumeci O Di Iorio G Siciliano G Donati MA Carubbi F Ermani M Mongini T

Toscano A Italian GSDII Group

J Neurol 2012 May259(5)952-8

Causistry 33 males and 41 females (MF = 081

mean age first symptoms 283 yrs (2-55) mean age study entry 43 yrs (7-72 )

7 wheelchair bound 27 ventilation support

Clinical assessment included 6MWT FVC Walton and Gardner-Medwin score the

number of hours of ventilation BMI echocardiography and CK

After treatment

bull increase 6MWT in 4858 (83) mean increase of 63 m After treatment in

bull improved or unchanged FVC in 4569 (65)

bull reduced ventilatory support from 156 to 12

bull 6 patients stopped mechanical ventilation and two others started it

FBL born 041993

Jan 2005 March 2007 July 2007

FBL born 041993

May 2006 May 2007

Giovanni CianaLaura DeromaAnnalisa SechiRosi Da RiolDaniela MacorKatja Bianchi

Giulia LivaSerena Valent

Andrea DardisStefania ZampieriSilvia CattarossiIrene ZaninErika MaliniMilena RomanelloAnnalisa Pianta

Marco Confalonieri

Federica Edith Pisa

Regional Coordinator Centre for Rare Disorders University Hospital of Udine

Pulmonary Unit University Hospital of Trieste

Inst of Hygiene and Epidemiology University Hospital of Udine

FBL born 041993

May 2006 May 2007

Giovanni CianaLaura DeromaAnnalisa SechiRosi Da RiolDaniela MacorKatja Bianchi

Giulia LivaSerena Valent

Andrea DardisStefania ZampieriSilvia CattarossiIrene ZaninErika MaliniMilena RomanelloAnnalisa Pianta

Marco Confalonieri

Federica Edith Pisa

Regional Coordinator Centre for Rare Disorders University Hospital of Udine

Pulmonary Unit University Hospital of Trieste

Inst of Hygiene and Epidemiology University Hospital of Udine

Giovanni CianaLaura DeromaAnnalisa SechiRosi Da RiolDaniela MacorKatja Bianchi

Giulia LivaSerena Valent

Andrea DardisStefania ZampieriSilvia CattarossiIrene ZaninErika MaliniMilena RomanelloAnnalisa Pianta

Marco Confalonieri

Federica Edith Pisa

Regional Coordinator Centre for Rare Disorders University Hospital of Udine

Pulmonary Unit University Hospital of Trieste

Inst of Hygiene and Epidemiology University Hospital of Udine