Case Discussion Pompe Disease 2003. 06. 30.

1. Case DiscussionPompe Disease2003. 06. 30. Ri 許哲偉 Ri 李秉學

2. Brief History • This is a 1-year-old boy, G1P1, GA 39+5 wk, NSD, BBW 3178 gm. • When he was 2 months old in Sep., 2002, he had cough, rhinorrhea, decreased appetite and activity, and he was admitted to 中國 hospital. • Cardiomegaly and hypotonia were noted and Pompe’s disease was suspected.

3. Brief History • 9/19/2002, in NTU, liver enzyme, cardiac enzyme, LDH level all increased. • Echo: hypertrophic cardiomyopathy、moderate LVOT obstruction, severe MR, mild TR, PFO. • Enzyme assays of lymphocyte, skin fibroblast and urine revealed prominent decreased α- glucosidase level.

5. Hospitalization

6. Chief Complaint • High fever (40℃) with tachycardia for 2 days. • Acrocyanosis、chills、tachypnea、decreased urine output、dry lips were also noted. • Low grade fever with productive cough for 3 wks. Present Illness

7. Consul-tation Note

10. Anesthetic Record

11. Glycogen Storage Disease and Pompe Disease

12. Glycogen Storage Disease • Inherited disorders affecting glycogen metabolism. • Virtually all enzymes involved in its synthesis, degradation, and regulation cause some type of GSD. • Abnormal quantity and quality of glycogen. • Classified by organ involvement and clinical manifestation into liver and muscle glycogenoses.

13. Glycogen Storage Disease • More than 12 forms of glycogenoses. • 1/20,000 in live births. • Most common in childhood Deficiency of G-6-P (type I), lysosomal acid α- glucosidase (type II), debrancher (type III), and liver phosphorylase kinase. • Most common in adulthood Myophosphorylase deficiency (type V)

15. Pompe Disease (Type II) • Deficient activity of lysosomal acid α-1,4 glucosidase (acid maltase). • Accumulation of glycogen in lysosomes. • 1/50,000 in live births without ethnic prediction. • An autosomal recessive disorder, chromosome 17q23.

16. Clinical Manifestations Infantile form • Most severe, prominent cardiomegaly, hypotonia, and death prior to 2 yr of age. • “Floppy baby,” feeding difficulties, macroglossia, hepatomegaly, and heart failure due to hypertrophic cardiomyopathy. • ECG: high-voltage QRS, shortened P-R interval. • Death results from cardiorespiratory failure or aspiration pneumonia.

17. Clinical Manifestations Juvenile form • Delayed motor milestones, difficult walking, followed by swallowing difficulties, weakness of proximal muscle and respiratory muscle. • Death from respiratory failure before 20 yrs old. • Cardiomegaly is variable, and overt cardiac failure.

18. Clinical Manifestations Adult form • Slow progressive myopathy without cardiac involvement. • Onset between 2nd and 7th decades. • Proximal muscle weakness with trunk involvement. (pelvic girdle, paraspinal muscle, diaphragm are the most seriously affected) • Initial symptoms: respiratory insufficiency (somnolence, morning headache, orthopnea, and exertional dyspnea)

19. Laboratory Findings • Elevated levels of serum creatine kinase, AST, and LDH. • Muslce biopsy shows presence of vacuoles stained positive with glycogen. • Electron microscopy reveals glycogen accumulation within the membranous sac and in the cytoplasm. • EMG reveals myopathic features with excessive electrical irritability of muscle fibers.

20. Diagnosis • Decreased levels of acid α- glucosidase activity in muscle or cultured skin fibroblast. • Deficiency is more severe in the infantile form. • Prenatal diagnosis using amniocytes or chronic villi is available in the fatal infantile form.

21. Therapeutic approach to Pompe disease 1。Enzyme replacement therapy 2。Gene therapy

22. Enzyme replacement therapy

23. Enzyme replacement therapy

24. Gene therapy Provide a permanent internal source of enzyme

25. Gene therapy • Still in the early stage of investigation • Adenovirus carrying GAA(acid alpha glucosidase) was examined by intramuscular, intracardiac and intravenous administration • Correction of enzyme deficiency in In Vivo experiments

26. Anesthesia and Pompe disease

27. Major anesthetic problems • The cardiomyopathy • Oxygenation • Respiratory muscle weakness and the use of muscle relaxant

28. The cardiomyopathy • Massive infiltration of the ventricular wall may produce either a congestive or obstructive cardiomyopathy • Avoidance of myocardial depression and vasodilator • Using ketamine and sevoflurane seems to be reasonable

29. Oxygenation • Some children with Pompe disease have large toungues →might cause loss of airway control during anesthesia • Due to the cardiomegaly and weak respiratory muscle, patients have increased vulnerability to atelectasis and aspiration

30. Respiratory muscle weakness and muscle relaxants • Increased susceptibility to prolonged intubation after operation • Succinylcholine may cause rhabdomyolysis, hyperkalemia and cardiac arrest in children with undiagnosed myopathies.

31. Ureteroscopic removal of left ureteral lithiasis in a patient with acid maltase deficiency diseaseANESTH ANALG 1993;76:662-4 • A 71-year old patient with adult type of AMD come for removal of ureteral stone • Induction of anesthesia proceeded by propofol(100mg, IV) ,atracurim(35mg) • Ketorolac(60mg, IM) was injected • Anesthesia was maintained by 66% nitrous oxide and IV propofol infusion • Neuromuscular block was reversed by neostigmine and glycopyrrolate

32. Ureteroscopic removal of left ureteral lithiasis in a patient with acid maltase deficiency diseaseANESTH ANALG 1993;76:662-4 • The selection of drug was based on minimizing post.OP drowsiness, muscle weakness, and the respiratory depressant effect of anesthetics • Propofol was selected for its short recovery and post.operative stay • Narcotics were avoided and ketorolac was used for analgesia • Depolarizing muscle relaxant was considered unsafe

33. Prolonged respiratory depression after anesthesia for parathyroidectomy in patient with Juvenile AMD Journal of Clinical Anes.,Vol.8 1996 • 11 year-old boy with juvenile AMD and primary hyperparathyroidism undergoing parathyroidectomy • Anesthesia was induced by mask with enflurane, N2O and oxygen • Despite of avoidance of any muscle relaxant,the patient develop post.OP respiratory failure and was kept intubated until the 15th day after surgery

34. Conclusions • Avoid cardiac depressants and vasodilators • Keep PEEP and high FiO2 • Close monitoring post.OP condition

35. Thank you for your attention