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Home , Glycogen storage disease, Oral medicine

Oral manifestationsand anesthesiaconsiderations in a child with glycogenstorage disease type lb: case report

Joseph Katz, DMDZe’ev Shenkman, MD Mordechai Sela, DMD Meir Rakotz, DMDBen-Zion Garty, MD

~,6 stora,ge disease (GSD)type la, known develop. ,which can be overt, can lead as von Gierke s disease, is a rare autosomalre- to secondary pyelonephritis and gout. is Hyperlipi- Glycogencessive inborn error of metabolism in which demia4,6 also maybe found in these patients. there is an inability to cleave to due The mechanismof the bleeding tendency is related to glucose 6-phosphatase (G6Pase) deficiency. 1, 2 The to impaired platelet function with prolonged bleeding diagnosis currently is established by demonstrating the time, reduced platelet adhesiveness, abnormal aggre- lack of G6Paseactivity in the patient’s biopsied gation, and impaired capacity to release adenosine specimen. Recently, however, a DNA-baseddiagnos- diphosphate in response to collagen or epinephrine.6, 7 tic technique was developed in which mutations in the These abnormalities can be corrected by improving the G6Pasegene can be identified in readily-available tis- metabolic16 state of the patient. sues such as blood and skin, and in the case of prena- The immunologicaldeficiency in patients with type tal testing, in chorionic villi or amniocytes.3 Typelb is lb GSDis attributed to neutropenia7-1° and/or dis- an autosomal recessive variant of von Gierke’s disease turbed neutrophil function due to impairment in mo- in which glucose 6-phosphate, a product of metabolic tility, 7, ~ migration,7-9 adherence/bactericidal capacity, cleavage of glycogen, cannot be transported to the in- superoxide anion production,17 and intracellular cal- ner surface of the microsomedue to a deficiency of its cium mobilization28 transport system, glucose 6-phosphate microsomal Oral manifestations of the disease include delayed translocase. Therefore, glucose 6-phosphate cannot be developmentof dentition, s, 11,12 rapidly progressive metabolized to glucose even though microsomal glu- periodontal disease,4, 7, 9 recurrent stomatitis, 9,10 oral cose 6-phosphatase activity is normaUThe diagnosis candidiasis,9,10oral ulcerations,4,10 and dental caries6, 9 of type lb is still based on liver biopsy and enzymatic and abscesses. 9 Treatment of oral lesions mayinclude assays. In both types, glycogen accumulates in several and anti-fungal rinses, as well as oral admin- organs, especially the liver1, 2, 4 and kidneysR,4, 5 Glu- istration of antibiotic agents. cose availability to various tissues is impaired,1, 2 and Perianesthetic managementmay be complicated by hypoglycemia2 and chronic ensue. several potential metabolic and homeostatic challenges Chronic metabolic acidosis can lead to negative calcium such as severe ,2 which can be masked by balance6 and . anesthetic medications,2 lactic acidosis,R,6 and bleeding Both types have manysystemic and oral manifesta- tendency.S,6 tions. The main systemic manifestations include Only a few case reports describe several anesthetic growthretardation, 1, 2, 4 ,1,4 renal enlarge- considerations in patients with type 1 GSD..6,13,14 None ment,1, 4, 5 bleedingdiathesis 2,s-7 manifestedby recurrent discriminated between the various subtypes of GSD epistaxis and bleeding after minor trauma or surger- type 1. Wereport a case of dental treatment under gen- ies,S, 6 recurrent episodes of severe hypoglycemia,R, s, 6 eral in a patient with GSDtype lb, describ- and metabolic acidosis. 2, 6 Patients with GSDtype lb ing the clinical presentation of this rare inborn error of also suffer from recurrent pyogenic due to metabolism and an approach to the dental and immunological7-1° deficiency. perianesthetic management. Other clinical manifestations, commonto both type la and lb, include possible brain damage6 and convul- * Sincethe originalsubmission, a case report distinguishing anes- sionsz s, 6 as a result of hypoglycemia,growth retarda- thetic considerationsin type 1 GSDhas been published. Please seeShenkman Z, Golub Y, MeretykY, Shir Y, LandauD, Landau tion,I, 2, 4 facial and truncal adiposity,is and delayed 1, ~ 6, PH:Anaesthetic managment in a patientwith glycogen storage puberty2 Hepatic adenomas and hepatomas is may diseasetype 1 b. CanJ Anaesth43:467-70, 1996.

PediatricDentistry- 19:2, 1997 AmericanAcademy of PediatricDentistry 123 Case report ventilated mechanically. Anesthesia was maintained with nitrous oxide 70% in oxygen and halothane. The History patient remained hemodynamically stable, oxygen- A 3-year-old female was admitted to the dental clinic ation and acid-base status were normal, and there were of Sheba Medical Center for treatment of dental caries. no episodes of hypoglycemia or excessive bleeding The patient was diagnosed previously as suffering from the extraction site. Application of local pressure from CSD type lb, manifested by hepatomegaly, hy- and biological glue were sufficient to control bleeding poglycemia, , recurrent infections (re- from the extraction site. Recovery after the 3.5 hr of current otitis media, several episodes of pneumonia, anesthesia was uneventful. furunculosis, and stomatitis), and , with 3 The following recommendations and maintenance absolute neutrophil count frequently below 500/mm . were proposed: a vigorous oral hygiene plan includ- The diagnosis had been confirmed by liver biopsy and ing instructions of the parents in toothbrushing tech- biochemical assays. Hypoglycemia was prevented by niques, hygienist inspection, individual fluoride trays, frequent meals and day and night feeding with un- mouth rinses enriched with fluoride and antimicrobial cooked cornstarch. rinses. In addition, the parents were instructed to Physical examination schedule 3-month follow-up visits in the dental clinic. The patient's weight was 10 kg (below the third Maintenance percentile) and her height was 80 cm (below the third Although the importance of follow-up visits in the percentile). The abdomen was distended, the lower dental clinic was stressed to the parents, we have not edge of liver was palpated 10 cm below the costal been able to see the patient because of frequent hospi- margin, with enlargement of the left lobe, and the talizations and poor compliance to dental follow-up. spleen was palpated 6 cm below the costal margin; Therefore, 3 years lapsed between the dental treatment cervical lymphadenopathy was noted. Extensive den- and her next dental examination, when oral ulcers had tal caries was noted. appeared. The oral pathological findings noted were: Laboratory findings scaling of the lips (Fig 1), recurrent neutropenic ulcer- Abnormal laboratory tests included: hemoglobin 9.8 ation of the lips and oral mucosa, a large neutropenic g/dl (normal 11.5-15.5); absolute neutrophil count 370/mm3 (5% of 7400 leukocytes, normal 1500-8000/ mm3); uric acid 6.6 mg/dl (normal up to 5.5); triglyc- erides 595 mg/dl (normal up to 200); lactic acid 24.1 mg/dl (normal up to 16.0); pyruvic acid 1.7 mg/dl (normal up to 0.8). Blood pH at the time was 7.41, with PCO2 37 mmHg and bicarbonate 24 mEq/L. Neutrophil function tests showed impaired chemotaxis, impaired superoxide formation after stimulation with formyl- methionyl-leucyl-phenylalanine (FMLP), and subopti- mal killing of staphylococci. Management Restoration and extraction were performed under general anesthesia due to the young age of the patient, Fig 1: The patient at age 6 years. Note scaling of the lips and the large ulcer on the inferior lateral her apprehensive behavior, and the length of the pro- aspect of the tongue. cedure. The patient was not premedicated. Preanes- thetic fasting lasted 4 hr, during which intravenous infusion of 10% glucose at a rate of 40 ml/hr was started. The same infusion continued during the opera- tion and after it, until resumption of oral feeding. Moni- toring consisted of ECG, noninvasive automatic arte- rial pressure, pulse oximetry, and CO2 capnography. Blood samples were drawn through an intravenous cannula for monitoring blood glucose concentrations and acid-base status. Anesthesia was induced with ni- trous oxide 70% in oxygen and halothane up to 2.5%, administered by a face mask. After an intravenous ad- ministration of atropine 0.15 mg, nasotracheal intuba- tion was accomplished using a 4.0-mm-internal-diam- eter preformed RAE tube, and the patient was Fig 2: Inflammation of the gingiva at age 6 years.

124 American Academy ofPediatric Pediatric Dentistry - 19:2, 1997 ulcer (1 cmin diameter) on the right lateral aspect bleeding into tissue spaces.6 Primary closure of extrac- the tongue, coated on its inferolateral aspect (Fig 1), and tion sites should be avoided to prevent the formation gingival inflammation (Fig 2). There was a delay of hematomata, and bleeding should be controlled by eruption time, as well as slight hypodontia of the pri- local measures including compression and packing mary teeth. Surprisingly, no caries was observed. The with hemostatic agents such as Gelfoam TM or oral ulcers were treated by 0.2% in aque- SurgicelTM.6 The anesthesiologist should be prepared ous solution mouthrinses, oral nystatin {100,000units for transfusion of homologousplatelets when needed. per 5 ml} and oracort E ( acetonide 0.1% Frequent feeding and high diet may and esracaine gel), resulting in partial improvement. lead to development of caries and materia alba accu- mulation, resulting in enamel decalcification. In addi- Discussion tion, chronic metabolic acidosis can contribute to the Specific anesthetic considerations in patients with formation of dental caries. The nature of the caries type lb GSDinclude risk of severe perioperative hy- would be circumferential as seen in rampant caries, poglycemia,2 lactic acidosis, 2 bleeding tendency2, 6 and especially on the buccal and lingual aspects. Therefore, immunologicaldeficiency. 7-1° In addition, mental retar- an intensive oral hygiene plan must be implemented. dation, if present,2 can disturb anesthetic induction and Fluoride enrichment in the form of trays and mouth recovery. rinses also maybe added to the maintenance plan. In Cannulations should be performed with meticulous the case of severe decalcification, crowns are recom- attention to aseptic techniques because of the immuno- mendedas the treatment of choice. The delayed devel- logical deficiency in these patients. opmentof dentition,~, 11,12 rapidly progressive periodon- Blood glucose concentrations must be monitored tal disease, 4, 7, 9 and the appearance of oral mucosa carefully since hypoglycemiacan be severe. 2 Preopera- ulcerations, which are neutropenic in origin, are char- tive fasting should be as brief as possible, and glucose- acteristic of the disease.4,10 Oral antimicrobialrinses also containing fluids, should be administered intrave- maybe added. In addition, 3-monthfollow-up visits in nously perioperatively 13, 14 at a rate equal to basal the dental clinic are of paramountimportance. metabolic requirements (4-8 mg/kg body weight/ Extraoral manifestations in our patient included min).19 Moreover, intraoperative hypoglycemia is po- hypoglycemia, failure to thrive, hepatomegaly, recur- tentially unrecognizable,a since anesthesia can maskits rent infections, neutropenia, impaired neutrophil func- clinical signs and symptoms. Hypoglycemic convul- tion, hyperuricemia, and hypertriglyceridemia. Our sions should be anticipated2 and treated by intravenous patient presented with dental caries, which is common infusion of glucose. in GSDpatients mainly because of the excessive Inasmuch as lactate cannot be metabolized com- amounts of oral glucose used to prevent hypoglycemia. pletely and converted to glycogen in patients with type Additional factors such as chronic metabolic acidosis lb GSD,2 lactic acidosis maydevelop. Therefore, blood mayhave contributed to the formation of dental caries. pH should be monitored and lactate-containing fluids The perianesthetic course was uneventful. There (e.g., lactated Ringer) should be avoided in these pa- was no hypoglycemia, acidosis, or major bleeding. It tients.2.14 It is preferable to ventilate these patients me- was decided not to cannulate a peripheral artery since chanically during anesthesia rather than permit spon- the procedure was not a major operation and was with- taneous ventilation, since spontaneous ventilation may out fluid shifts. Bloodglucose concentrations and acid- be6 inefficient and maylead to respiratory acidosis. base status were monitored by drawing blood from an Hyperventilation also should be avoided, as respi- intravenously placed cannula; normocapnea was af- ratory can lead to excessive release of lactate firmed by capnography. The careful oral feeding by the from muscles. Since the lactate cannot be metabolized patient’s parents, as well as perioperative glucose efficiently in patients with GSDtype lb, it mayaggra- supplementation, probably explains the lack of acido- vate the metabolic acidosis. 6 If metabolic acidosis does sis, since a balanced diet mayprevent the production occur, it should be treated with intravenous adminis- of excess amountsof lactic acid. In addition, the use of tration of sodium bicarbonate according to the base uncooked corn starch probably provided the patient deficit. A peripheral artery should be cannulated for with satisfactory glucose supplementation, especially major interventions in these patients to monitor arte- during sleep, since glucose derived from corn starch is rial blood acid-base status and glucose concentrations24 slowly and continuously absorbed from the bowel into The dental surgeon and the anesthesiologist have to the blood. consider the possibility of bleeding diathesis in patients During the follow-up period, delayed tooth devel- with GSDtype lb (see above). Various methods opment and neutropenic ulceration of the oral mucosa avoid excessive bleeding during in these pa- and gingiva appeared. Unexpectedly, no dental caries tients have been proposed, including meticulous pre- was observed. Oral lesions were treated by local anti- operative control of blood glucose concentrations by a septic irrigations to prevent secondarybacterial or funJ regulated diet or total parenteral nutrition. 6 Block an- gal infections. esthesia may be avoided when possible, to prevent

PediatricDentistry - 19:2,1997 AmericanAcademy of PediatricDentistry 125 Conclusion 6. Herzog S, WeisbergS, Blausten DI: Oral surgical manage- mentof a patient with glycogenstorage disease type I. J Oral In summary,type lb glycogen storage disease may Maxillofac Surg 44:999-1002,1986. pose difficult management problems both to the den- 7. AmbrusoDR, McCabeERB, Anderson D, Beaudet A, Ballas tal surgeon and the anesthesiologist. Careful attention LM,Brandt IK, et ah Infectious and bleeding complications in patients with glycogenosis lb. AmJ Dis Child 139:691- to aseptic techniques, normoglycemia, and acid base 97, 1985. status, and awareness of the possibility of bleeding and 8. Beaudet AL, Anderson DC, Michels VV, Arion WJ, Lange hematomata formation are needed to overcome these AJ: Neutropeniaand impaired neutrophil migration in type difficulties. IB glycogenstorage disease. J Pediatr 97:906-10,1980. 9. Koven NL, Clark MM,Cody CS, Stanley CA, Baker L, Dou- Dr. Katz is a lecturer in the Departmentof Oral Medicineat Sheba glas SD: Impaired chemotaxis and neutrophil (polymorpho- Medical Center, Tel Hashomer, and the HebrewUniversity -- nuclear leukocyte) function in glycogenosistype IB. Pediatr HadassahFaculty of Dental .Dr. Shenkmanis a lecturer Res 20:438-42,1986. in the Departmentof Anesthesiologyand Critical Care Medicine 10. McCabe ERB, Melvin TR, O’Brien D, Montgomery RR, and Dr. Sela is a Professor in the Departmentof Oral and Maxil- Robinson WA,Bhasker C, BrownBh Neutropenia in a pa- lofacial Rehabilitation, both at HadassahUniversity Hospital and tient with type IB glycogenstorage disease: in vitro response the HebrewUniversity -- HadassahFaculty of Dental Medicine. to lithium chloride. J Pediatr 97:944-46,1980. Dr. Rakotzis with the Divisionof Pediatric and Hospital Dentistry 11. Van Creveld S: Glycogen disease. Arch Dis Child 27:113- at ShebaMedical Center, Tel Hashomer,Israel. Dr. Garty is a Se- 20, 1952. nior Lecturer in the Departmentof and KipperInstitute 12. CudzinowskiL: VonGierke’s disease: report of case. ASDC of Immunologyat Schneider Children’s Medical Center of Israel J DentChild 45: 413-15, 1979. in PetachTikva, Israel. 13. BevanJC: Anaesthesia in VonGierke’s disease. Current ap- 1. Beaudet AL:The glycogen storage diseases. In: Harrison’s proach to management.Anaesthesia 35:699-702, 1980. Principles of , 10th ed. Petersdorf RGet 14. Cox JM: Anesthesia and glycogen-storage disease. al, Eds. NewYork: McGraw-HillBook Co, 1983, pp 539-45. Anesthesiol 29:1221-25, 1968. 2. Stoelting RK, Dierdorf SF: Metabolicand nutritional disor- 15. Ralls SA, Marshall EC:Dental managementof a patient with ders. In: Anesthesia and Co-Existing Disease, 3rd Ed. glycogen storage disease type I. J AmDent Assoc 110:723- Stoelting RK, Dierdorf SF, Eds. NewYork: Churchill 26, 1985. Livingstone, 1993, pp 375-92. 16. CzapekEE, DeykinD, SalzmanEW: Platelet dysfunction in 3. Lei K-J, ChenY-T, Chen H, WongL-JC, Liu J-L, McConkie- glycogenstorage disease type I. Blood41:235-47, 1973. Rosell A, Van Hove JLK, Ou C-YH,Yeh NJ, Pan LY, Chou 17. Gahr M, HeyneK: Impaired metabolic function of polymor- JY: Genetic basis of glycogenstorage disease type la: Preva- phonuclear leukocytes in glycogen storage disease lb. Eur lent mutations at the glucose-6-phosphatase locus. AmJ J Pediatr 140:329-30,1983. HumGenet 57:766-71, 1995. 18. Kilpatrick L, Garty BZ, Lundquist KF, Hunter K, Stanley 4. Barrett AP, Buckley DJ, Katelaris CH:Oral complications CA, Baker L, Douglas SD, Korchak MH:Impaired metabolic in type 1B glycogen storage disease. Oral Surg Oral Med function and signaling defects in phagocyticcells in glyco- Oral Pathol 69:174-76,1990. gen storage disease lb. J Clin Invest 86:196-202,1990. 5. LoevyHT, Matalon R, Rosenthal IM: Delayed dental age in 19. TonnesenAS: Crystalloids and colloids. In: Anesthesia, 3rd hepatorenal glycogen storage disease. J AmDent Assoc ed. Miller RD,(ed). NewYork: Churchill Livingstone, 1990, 107:944-46,1983. pp 1439-65.

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126 AmericanAcademy of Pediatric Dentistry PediatricDentistry - 19:2, 1997