Pompe’s DiseasePompe’s Disease

PGY PGY 尤善琦尤善琦Clerk Clerk 林敬為林敬為

Case reportCase report

Name:Name: 林林 XXXX Age:1 y/o 6 m/oAge:1 y/o 6 m/o Sex:maleSex:male Admission date:93/10/15Admission date:93/10/15 Chief complaint:progressive vomiting foChief complaint:progressive vomiting fo

r 10 daysr 10 days

Past history(I)Past history(I)

Birth Hx:G3P1AA2, C/S, BBW:3175gm, GA:Birth Hx:G3P1AA2, C/S, BBW:3175gm, GA:39+4 wks, DOIC(-), PROM(-), perinatal ins39+4 wks, DOIC(-), PROM(-), perinatal insult(-)ult(-)

Growth and development:Growth and development: DMS:general hypotoniaDMS:general hypotonia Roll over (+/-), sit without support (-)Roll over (+/-), sit without support (-)

Past history(II)Past history(II)

Past history:Past history: 3 admissions due to pneumonia in 3 admissions due to pneumonia in 門諾門諾 ,, 慈濟慈濟 92/8/9~92/10/3:NTUH for pompe’s disease92/8/9~92/10/3:NTUH for pompe’s disease 29 courses of enzyme replacement therapy be29 courses of enzyme replacement therapy be

tween 92/9/25~93/10/11tween 92/9/25~93/10/11 Jejunostomy on 93/3/10Jejunostomy on 93/3/10 Repeated aspiration pneumonia and UGI bleeRepeated aspiration pneumonia and UGI blee

ding during the period of ERTding during the period of ERT

Past history(III)Past history(III)

Maternal history:Maternal history: No drug/radiation exposure during pregnanNo drug/radiation exposure during pregnan

cycy Denied systemic diseaseDenied systemic disease

Family history:denied history of hereditaFamily history:denied history of hereditary diseasery disease

Present illness(I)Present illness(I) Decrease muscle tone was noted at 2 m/oDecrease muscle tone was noted at 2 m/o Scarf sign(+), heel to ear sign(-), DTR: all limb+Scarf sign(+), heel to ear sign(-), DTR: all limb+

+, muscular dystrophy+, muscular dystrophy Brain echo, MRI, EKG: no specific findingBrain echo, MRI, EKG: no specific finding GOT/GPT:278/163, CK:893GOT/GPT:278/163, CK:893 Muscle biopsy:PAS positiveMuscle biopsy:PAS positive 92/8/19, confirm pompe’s dz at NTUH92/8/19, confirm pompe’s dz at NTUH ERT 29 course during 92/10/3~93/10/11ERT 29 course during 92/10/3~93/10/11

Present illness(II)Present illness(II)

N/V with diarrhea for 10 days after the jeN/V with diarrhea for 10 days after the jejunostomy tube was changedjunostomy tube was changed

Shortness of breath and irritability was nShortness of breath and irritability was notedoted

Admission under the impression of AGEAdmission under the impression of AGE

Physical examination(I)Physical examination(I) Consciousness:clearConsciousness:clear HEENT:grossly normal,conjunctiva: not HEENT:grossly normal,conjunctiva: not

pale, sclera: anicteric, pupil:isocoric, lighpale, sclera: anicteric, pupil:isocoric, light reflex:+/+, eardrum:not injected, thorat:t reflex:+/+, eardrum:not injected, thorat:not injected, macroglossianot injected, macroglossia

Neck:supple, JVE(-), LAP(-)Neck:supple, JVE(-), LAP(-) Chest:symmetric expansion, subcostal rChest:symmetric expansion, subcostal r

etraction(+), BS:coarse rhonchietraction(+), BS:coarse rhonchi

Physical examination(II)Physical examination(II)

Heart:RHB, hyperdynamic heart, Gr. II/IV Heart:RHB, hyperdynamic heart, Gr. II/IV systolic murmur over LSBsystolic murmur over LSB

Abdomen:soft, tenderness(-), rebound pAbdomen:soft, tenderness(-), rebound pain(-), normoactive bowel sound, liver: 2 ain(-), normoactive bowel sound, liver: 2 fb below RCM, jejunostomyfb below RCM, jejunostomy

Extremites:flaccid, edema(-), cyanosis(-),Extremites:flaccid, edema(-), cyanosis(-), petechiae(-), DTR(-) petechiae(-), DTR(-)

Preoperative conditionPreoperative condition

Respiratory failure under biPAPRespiratory failure under biPAP TPN to support nutritionTPN to support nutrition 10/18 consult pediatric surgeon for fund10/18 consult pediatric surgeon for fund

oplication and pyloroplasty due to recuroplication and pyloroplasty due to recurrent aspiration and mild GERrent aspiration and mild GER

10/22 operation performed10/22 operation performed

Anesthesia recordAnesthesia record

Propofol, ketamine, Nimbex, SCCPropofol, ketamine, Nimbex, SCC OO22, air with sevoflurane, air with sevoflurane Intubation:smoothlyIntubation:smoothly

Pompe’s diseasePompe’s disease

Glycogen storage disease type IIGlycogen storage disease type II acid maltase deficiencyacid maltase deficiency Deficiency of acid α-glucosidase (GAA)Deficiency of acid α-glucosidase (GAA) Lysosomal glycogen accumulation in carLysosomal glycogen accumulation in car

diac, skeletal, smooth muscle cells, liver, diac, skeletal, smooth muscle cells, liver, and CNSand CNS

Subset and incidenceSubset and incidence

Infantile-onset:< 1 y/oInfantile-onset:< 1 y/o Late-onset:> 1 y/o, juvenile-onset and adLate-onset:> 1 y/o, juvenile-onset and ad

ult-onsetult-onset Combined incidence of all forms:1:40000Combined incidence of all forms:1:40000 Infantile-onset prominent in TaiwanInfantile-onset prominent in Taiwan

Clinical presentation(I)Clinical presentation(I) Gene locus on chromosome 17q25Gene locus on chromosome 17q25 autosomal recessiveautosomal recessive Age of onset, organ involvement, rate of Age of onset, organ involvement, rate of

progression—determined by residual GAprogression—determined by residual GAA activity and environmental influencesA activity and environmental influences

Residual GAA activity:Residual GAA activity: infantile-onset:<1%infantile-onset:<1% late-onset:children and juveniles:1~10%late-onset:children and juveniles:1~10% adults:2~40%adults:2~40%

Clinical presentation(II)Clinical presentation(II)

Floppy baby appearance, head lag, axial Floppy baby appearance, head lag, axial hypotonia, laxity of facial muscleshypotonia, laxity of facial muscles

Moderate hepatomegaly (82% of p’ts)Moderate hepatomegaly (82% of p’ts) Macroglossia (62% of p’ts)Macroglossia (62% of p’ts) Feeding difficulties and poor weight gaiFeeding difficulties and poor weight gai

nn Delayed motor milestonesDelayed motor milestones

Clinical presentation(III)Clinical presentation(III)

Cardiomegaly and cardiomyopathy (95Cardiomegaly and cardiomyopathy (95%)%) Thickening of the walls of both ventricles anThickening of the walls of both ventricles an

d interventricular septumd interventricular septum Hypertrophic cardiomyopathyHypertrophic cardiomyopathydilated cardilated car

diomyopathydiomyopathy Obstruction of the left ventricular outflow trObstruction of the left ventricular outflow tr

act act

Clinical presentation(IV)Clinical presentation(IV)

MyopathyMyopathy Rapidly progressive muscle weakness (96%) in Rapidly progressive muscle weakness (96%) in

the trunk, lower limbs, and diaphragmthe trunk, lower limbs, and diaphragm Respiratory failureRespiratory failure

Respiratory distress or insufficiency with increRespiratory distress or insufficiency with increased work of breathingased work of breathing

Frequent respiratory infections and aspirationFrequent respiratory infections and aspiration Left lower lobe collapseLeft lower lobe collapse

Diagnosis(I)Diagnosis(I) Blood chemistryBlood chemistry

CK elevation (as high as 2000 UI/L)CK elevation (as high as 2000 UI/L) Aspartate aminotransferase, alanine aminotAspartate aminotransferase, alanine aminot

ransferase, lactate dehydrogenaseransferase, lactate dehydrogenase EMGEMG

Myopathic patternMyopathic pattern Pseudomyotonic discharges, fibrillation potPseudomyotonic discharges, fibrillation pot

enials, positive sharp waves, and excess eleenials, positive sharp waves, and excess electrical irritability ctrical irritability

Diagnosis(II)Diagnosis(II)

Chest imaging studiesChest imaging studies Massive cardiomegalyMassive cardiomegaly

EKGEKG Shorten of PR intervalShorten of PR interval Broad QRS complexesBroad QRS complexes

Acid α-glucosidase assayAcid α-glucosidase assay Muscle or skin biopsyMuscle or skin biopsy

Disease management(I)Disease management(I) Respiratory support:Respiratory support:

Mechanical ventilationMechanical ventilation Frequent oral or deep nasal suctionFrequent oral or deep nasal suction

Treatment of cardiomyopathyTreatment of cardiomyopathy Beta blockers for outflow tract obstructionBeta blockers for outflow tract obstruction

Dietary therapyDietary therapy Early initiation of tube feedingEarly initiation of tube feeding

Physical therapyPhysical therapy

Disease management(II)Disease management(II)

Enzyme replacement therapyEnzyme replacement therapy Clinical trials phase IIClinical trials phase II Decrease cardiomegalyDecrease cardiomegaly Improve cardiac and skeletal muscle functioImprove cardiac and skeletal muscle functio

nn Prolong survivalProlong survival

Compared with this patientCompared with this patient

Muscle tone ↓ at 2 m/o Muscle tone ↓ at 2 m/o infantile-onset infantile-onset General hypotonia, delayed motor milestoGeneral hypotonia, delayed motor milesto

ne, hepatomegaly, macroglossiane, hepatomegaly, macroglossia CK level↑(893)CK level↑(893) Hypertrophic cardiomyopathyHypertrophic cardiomyopathy Repeated aspiration pneumonia, subcostaRepeated aspiration pneumonia, subcosta

l muscle retractionl muscle retractionrespiratory muscle wrespiratory muscle weaknesseakness