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Chapter 17 - Disorders of Intermediaries of Metabolism and Malignant Hyperthermia

Published online by Cambridge University Press:  26 January 2024

By
David B. MacLean  and
Stephen H. Halpern
Edited by
David R. Gambling ,
M. Joanne Douglas  and
Grace Lim
David R. Gambling
Affiliation:
University of California, San Diego
M. Joanne Douglas
Affiliation:
University of British Columbia, Vancouver
Grace Lim
Affiliation:
University of Pittsburgh
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Summary

Many inherited conditions result from disorders of intermediary metabolism. Many more are discovered annually using advanced gene sequencing and other tools. These diseases cause symptoms because of the accumulation of precursors, absence of the final product, excessive toxic intermediaries, or a combination of all three mechanisms. Many are fatal in childhood, but some are compatible with adult life and pregnancy. A better understanding of the enzymatic deficiencies and new technologies have made recombinant enzyme replacement therapy possible. Along with early diet manipulation, current management allows many patients to live relatively normal lives. Because fertility may not be affected, some of these conditions will be encountered by the anesthesiologist. This chapter describes diseases caused by certain enzyme deficiencies and the by-products that cause symptoms. Some are exacerbated by pregnancy and the stress of labor and delivery. The anesthesiologist plays an essential role in reducing physiologic stress and avoiding triggering agents and routines that cause severe metabolic derangements or cardiopulmonary decompensation. The final portion of the chapter describes the most recent advances in the prevention and treatment of malignant hyperthermia in pregnancy, discussing the impact on mother and baby.

Keywords

glycogen storage diseaseslysosomal storage diseasesamino acid metabolismporphyriamalignant hyperthermiaanesthesiapregnancy
Type
Chapter
Information
Obstetric Anesthesia and Uncommon Disorders , pp. 273 - 289
Publisher: Cambridge University Press
Print publication year: 2024

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References

Wilcox, G. Impact of pregnancy on inborn errors of metabolism. Rev Endocr Metab Disord 2018;19:13–33.Google Scholar
Hicks, J, Wartchow, E, Mierau, G. Glycogen storage diseases: a brief review and update on clinical features, genetic abnormalities, pathologic features, and treatment. Ultrastruct Patho. 2011;35:183–196.Google Scholar
Ferns, JM, Halpern, SH. diseases, Glycogen storage. In Mankowitz, SKW (Ed.), Consults in Obstetric Anesthesiology. New York, NY: Springer, 2018: 235–240.Google Scholar
Veiga-da-Cunha, M, Gerin, I, Van Schaftingen, E. How many forms of glycogen storage disease type I? Eur J Pediatr 2000;159:314–318.Google Scholar
Grunert, SC, Rosenbaum-Fabian, S, Hannibal, L, et al. Three successful pregnancies in a patient with glycogen storage disease type 0. JIMD Rep 2021;57:38–43.Google Scholar
Karabul, N, Berndt, J, Kornblum, C, et al. Pregnancy and delivery in women with Pompe disease. Mol Genet Metab 2014;112:148–153.Google Scholar
Aeppli, TRJ, Rymen, D, Allegri, G, et al. Glycogen storage disease type VI: clinical course and molecular background. Eur J Pediatr 2020;179:405–413.Google Scholar
Cilliers, HJ, Yeo, ST, Salmon, NP. Anaesthetic management of an obstetric patient with Pompe disease. Int J Obstet Anesth 2008;17:170–173.Google Scholar
Shah, NM, Sharma, L, Ganeshamoorthy, S, et al. Respiratory failure and sleep-disordered breathing in late-onset Pompe disease: a narrative review. J Thorac Dis 2020;12:S235–S247.Google Scholar
Goker-Alpan, O, Kasturi, VG, Sohi, MK, et al. Pregnancy outcomes in late onset Pompe disease. Life 2020;10:194.Google Scholar
Park, S-K, Bae, J, Yoo, S, et al. Ultrasound-assisted versus landmark-guided spinal anesthesia in patients with abnormal spinal anatomy: a randomized controlled trial. Anesth Analg 2020;130:787–795.Google Scholar
Gurrieri, C, Sprung, J, Weingarten, TN, et al. Patients with glycogen storage diseases undergoing anesthesia: a case series. BMC Anesthesiol 2017;17:134. https://doi.org/10.1186/s12871-017-0428-xGoogle Scholar
Moustafa, S, Patton, DJ, Connelly, MS. Unforeseen cardiac involvement in McArdle’s disease. Heart Lung Circ 2013;22:769–771.Google Scholar
Carballeira, EMC, Vila, EF, Martíneza MJC, . Pregnancy control and management of labor in McArdle’s disease. Prog Obstet Ginecol 2008;51:307–310.Google Scholar
Johnson MS, . McArdle disease. Anästh Intensivmed 2020;61:S378–385.Google Scholar
Bollig, G, Mohr, S, Raeder, J. McArdle’s disease and anaesthesia: case reports. Review of potential problems and association with malignant hyperthermia. Acta Anaesthesiol Scand 2005;49:1077–1083.Google Scholar
Findlay, S, Liu, D, Rijhsinghani, A. Acute compartment syndrome: clinical course and laboratory findings in pregnant patients with McArdle’s Disease. Pain Med 2014;15:481–482.Google Scholar
Martens, DH, Rake, JP, Schwarz, M, et al. Pregnancies in glycogen storage disease type Ia. Am J Obstet Gynecol 2008;198:646 e1–7.Google Scholar
Dagli, AI, Lee, PJ, Correia, CE, et al. Pregnancy in glycogen storage disease type Ib: gestational care and report of first successful deliveries. J Inherit Metab Dis 2010;33:S151–S157.Google Scholar
Ferrecchia, IA, Guenette, G, Potocik, EA, et al. Pregnancy in women with glycogen storage disease Ia and Ib. J Perinat Neonatal Nurs 2014;28:26–31.Google Scholar
Reynolds, F. Fetal and maternal lactate increase during active second stage of labour (what about the effect of maternal analgesia?). BJOG 2003;110:86.Google Scholar
Ramachandran, R, Wedatilake, Y, Coats, C, et al. Pregnancy and its management in women with GSD type III – a single centre experience. J Inherit Metab Dis 2012;35:245–251.Google Scholar
Grunert, SC, Rosenbaum-Fabian, S, Hannibal, L, et al. Successful pregnancy in a woman with glycogen storage disease type 6. Mol Genet Metab Rep 2021;27:100770.Google Scholar
Bouwman, MG, Rombach, SM, Schenk, E, et al. Prevalence of symptoms in female Fabry disease patients: a case-control survey. J Inherit Metab Dis 2012;35:891–898.Google Scholar
Platt FM, d’Azzo A, Davidson, BL, et al. Lysosomal storage diseases. Nat Rev Dis Primers 2018;4:27. https://doi.org/10.1038/s41572-018–0025–4Google Scholar
Gary, SE, Ryan, E, Steward, AM, et al. Recent advances in the diagnosis and management of Gaucher disease. Expert Rev of Endocrinol Metab 2018;13:107–118.Google Scholar
Stirnemann, J, Belmatoug, N, Camou, F, et al. A review of Gaucher disease pathophysiology, clinical presentation and treatments. Int J Mol Sci 2017; 18(2):441. https://doi.org/10.3390/ijms18020441Google Scholar
Lau, H, Belmatoug, N, Deegan, P, et al. Reported outcomes of 453 pregnancies in patients with Gaucher disease: an analysis from the Gaucher outcome survey. Blood Cells Mol Dis 2018;68:226–231.Google Scholar
Rosenbaum, H. Management of women with Gaucher disease in the reproductive age. Thromb Res 2015;135:S49–S51.Google Scholar
Elstein, Y, Eisenberg, V, Granovsky-Grisaru, S, et al. Pregnancies in Gaucher disease: a 5-year study. Am J Obstet Gynecol 2004;190:435–441.Google Scholar
Ioscovich, A, Elstein, Y, Halpern, S, et al. Anesthesia for obstetric patients with Gaucher disease: survey and review. Int J Obstet Anesth 2004;13:244–250.Google Scholar
Komninaka, V, Flevari, P, Marinakis, T, et al. Outcomes of pregnancies in patients with Gaucher disease: the experience of a center of excellence on rare metabolic Disease-Gaucher disease, in Greece. Eur J Obstet Gynecol Reprod Biol 2020;254:181–187.Google Scholar
Tharp, WG, Farhang, B. Thromboelastography before epidural placement in a thrombocytopenic parturient with Gaucher disease treated with imiglucerase: a case report. A A Pract 2018;11:16–18.Google Scholar
Elstein, D, Klutstein, MW, Lahad, A, et al. Echocardiographic assessment of pulmonary hypertension in Gaucher’s disease. Lancet 1998;351:1544–1546.Google Scholar
Miller, JJ, Kanack, AJ, Dahms, NM. Progress in the understanding and treatment of Fabry disease. Biochimica Et Biophysica Acta-Gen Subj 2020;1864:129437.Google Scholar
Holmes, A, Laney, D. A retrospective survey studying the impact of Fabry disease on pregnancy. In Zschocke, J, Baumgartner, M, Morava, E, et al. (Eds.), JIMD Reports, Vol. 21. London: Springer, 2015: 57–63.Google Scholar
Parent, E, Wax, JR, Smith, W, et al. Fabry disease complicating pregnancy. J Matern Fetal Neonatal Med 2010;23:1253–1256.Google Scholar
Madsen, CV, Christensen, EI, Nielsen, R, et al. Enzyme replacement therapy during pregnancy in Fabry patients: review of published cases of live births and a new case of a severely affected female with Fabry disease and pre-eclampsia complicating pregnancy. JIMD Rep 2019;44:93–101.Google Scholar
Blau, N, van Spronsen, FJ, Levy, HL. Phenylketonuria. Lancet 2010;376:1417–1427.Google Scholar
Anonymous. Management of women with phenylalanine hydroxylase deficiency (phenylketonuria): ACOG Committee Opinion, No. 802. Obstet Gynecol 2020;135:e167–e170.Google Scholar
Muntau, AC, Adams, DJ, Belanger-Quintana, A, et al. International best practice for the evaluation of responsiveness to sapropterin dihydrochloride in patients with phenylketonuria. Mol Genet Metab 2019;127:1–11.Google Scholar
Sacharow, SJPJ, Levy, HL. Homocystinuria caused by cystathionine beta-synthase deficiency. In Adam, MPAH, Pagon, RA (Eds.). GeneReviews® [Internet]. 1993–2021. Updated May 18, 2017. Seattle (WA): University of Seattle.Google Scholar
Manta-Vogli, PD, Schulpis, KH, Dotsikas, Y, et al. Nutrition and medical support during pregnancy and lactation in women with inborn errors of intermediary metabolism disorders (IEMDs). J Pediatr Endocrinol Metab 2020;33: 5–20.Google Scholar
Horlocker, TT, Vandermeuelen, E, Kopp, SL, et al. Regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy: American Society of Regional Anesthesia and Pain Medicine Evidence-Based Guidelines (4th ed.). Reg Anesth Pain Med 2018;43:263–309.Google Scholar
Luzardo, GE, Karlnoski, RA, Williams, B, et al. Anesthetic management of a parturient with hyperhomocysteinemia. Anesth Analg 2008;106:1833–1836.Google Scholar
Puy, H, Gouya, L, Deybach, JC. Porphyrias. Lancet 2010;375:924–937.Google Scholar
Singal, AK. Porphyria cutanea tarda: recent update. Mol Genet Metab 2019;128:271–281.Google Scholar
Gandhi Mehta, RK, Caress, JB, Rudnick, SR, et al. Porphyric neuropathy. Muscle Nerve 2021;64:140–152.Google Scholar
Wilson-Baig, N, Badminton, M, Schulenburg-Brand, D. Acute hepatic porphyria and anaesthesia: a practical approach to the prevention and management of acute neurovisceral attacks. BJA Educ 2021;21:66–74.Google Scholar
Elder, G, Harper, P, Badminton, M, et al. The incidence of inherited porphyrias in Europe. J Inherit Metab Dis 2013;36:849–857.Google Scholar
Hift, RJ, Meissner, PN. An analysis of 112 acute porphyric attacks in Cape Town, South Africa: evidence that acute intermittent porphyria and variegate porphyria differ in susceptibility and severity. Medicine (Baltimore) 2005;84:48–60.Google Scholar
Marsden, JT, Rees, DC. A retrospective analysis of outcome of pregnancy in patients with acute porphyria. J Inherit Metab Dis 2010;33:591–596.Google Scholar
Shenhav, S, Gemer, O, Sassoon, E, et al. Acute intermittent porphyria precipitated by hyperemesis and metoclopramide treatment in pregnancy. Acta Obstet Gynecol Scand 1997;76:484–485.Google Scholar
Tollanes, MC, Aarsand, AK, Sandberg, S. Excess risk of adverse pregnancy outcomes in women with porphyria: a population-based cohort study. J Inherit Metab Dis 2011;34:217–223.Google Scholar
Harris, C, Hartsilver, E. Anaesthetic management of an obstetric patient with variegate porphyria. Int J Obstet Anesth 2013;22:156–160.Google Scholar
Rüffert, H, Bastian, B, Bendixen, D, et al. Consensus guidelines on perioperative management of malignant hyperthermia suspected or susceptible patients from the European Malignant Hyperthermia Group. Br J Anaesth 2021;126:120–130.Google Scholar
Dexter, F, Epstein, RH, Wachtel, RE, et al. Estimate of the relative risk of succinylcholine for triggering malignant hyperthermia. Anesth Analg 2013;116:118–22.Google Scholar
Biesecker, LG, Dirksen, RT, Girard, T, et al. Genomic screening for malignant hyperthermia susceptibility. Anesthesiology 2020;133:1277–1282.Google Scholar
Robinson, R, Carpenter, D, Shaw, MA, et al. Mutations in RYR1 in malignant hyperthermia and central core disease. Hum Mutat 2006;27:977–989.Google Scholar
Beam, TA, Loudermilk, EF, Kisor, DF. Pharmacogenetics and pathophysiology of CACNA1S mutations in malignant hyperthermia. Physiol Genomics 2017;49:81–87.Google Scholar
Lu, Z, Rosenberg, H, Li, G. Prevalence of malignant hyperthermia diagnosis in hospital discharge records in California, Florida, New York, and Wisconsin. J Clin Anesth 2017;39:10–14.Google Scholar
Lu, Z, Rosenberg, H, Brady, JE, et al. Prevalence of malignant hyperthermia diagnosis in New York State ambulatory surgery center discharge records 2002 to 2011. Anesth Analg 2016;122:449–453.Google Scholar
Ibarra Moreno, CA, Hu, S, Kraeva, N, et al. An assessment of penetrance and clinical expression of malignant hyperthermia in individuals carrying diagnostic ryanodine receptor 1 gene mutations. Anesthesiology 2019;131:983–991.Google Scholar
Guglielminotti, J, Rosenberg, H, Li, G. Prevalence of malignant hyperthermia diagnosis in obstetric patients in the United States, 2003 to 2014. BMC Anesthesiol 2020;20:19. https://doi.org/10.1186/s12871-020-0934-0Google Scholar
Schneiderbanger, D, Johannsen, S, Roewer, N, et al. Management of malignant hyperthermia: diagnosis and treatment. Ther Clin Risk Manag 2014;10:355–362.Google Scholar
Litman, RS, Smith, VI, Larach, MG, et al. Consensus statement of the Malignant Hyperthermia Association of the United States on unresolved clinical questions concerning the management of patients with malignant hyperthermia. Anesth Analg 2019;128:652–659.Google Scholar
Johnson, C. Pregnancy and malignant hyperthermia. J Clin Anesth 1992;4:173.Google Scholar
Kern-Goldberger, AR, Polin, M, Bank, TC, et al. Searching for a biochemical correlate of critical illness in obstetrics: a descriptive study of maternal lactate in patients presenting for acute care in pregnancy. J Matern Fetal Neonatal Med 2020;2020:1–3.Google Scholar
Zaigham, M, Helfer, S, Kristensen, KH, et al. Maternal arterial blood gas values during delivery: effect of mode of delivery, maternal characteristics, obstetric interventions and correlation to fetal umbilical cord blood. Acta Obstet Gynecol Scand 2020;99:1674–1681.Google Scholar
Rosenberg, H, Pollock, N, Schiemann, A, et al. Malignant hyperthermia: a review. Orphanet J Rare Dis 2015;10:93.Google Scholar
Larach, MG, Localio, AR, Allen, GC, et al. A clinical grading scale to predict malignant hyperthermia susceptibility. Anesthesiology 1994;80:771–779.Google Scholar
Schieren, M, Defosse, J, Böhmer, A, et al. Anaesthetic management of patients with myopathies. Eur J Anaesthesiol 2017;34:641–649.Google Scholar
Capacchione, JF, Muldoon, SM. The relationship between exertional heat illness, exertional rhabdomyolysis, and malignant hyperthermia. Anesth Analg 2009;109: 1065–1069.Google Scholar
Hopkins, PM, Rüffert, H, Snoeck, MM, et al. European Malignant Hyperthermia Group guidelines for investigation of malignant hyperthermia susceptibility. Br J Anaesth 2015;115:531–539.Google Scholar
(MHAUS) Managing a crisis: emergency treatment for an acute MH event: Malignant Hyperthermia Association of the United States (MHAUS). 2021. Available from: www.mhaus.org/healthcare-professionals/managing-a-crisis/ [last accessed September 29, 2022].Google Scholar
Glahn, KPE, Bendixen, D, Girard, T, et al. Availability of dantrolene for the management of malignant hyperthermia crises: European Malignant Hyperthermia Group guidelines. Br J Anaesth 2020;125:133–140.Google Scholar
Glahn, KP, Ellis, FR, Halsall, PJ, et al. Recognizing and managing a malignant hyperthermia crisis: guidelines from the European Malignant Hyperthermia Group. Br J Anaesth 2010;105:417–420.Google Scholar
Sim, AT, White, MD, Denborough, MA. The effect of oxytocin on porcine malignant hyperpyrexia susceptible skeletal muscle. Clin Exp Pharmacol Physiol 1987;14: 605–610.Google Scholar
Schuster, F, Johannsen, S. Maligne Hyperthermie und Schwangerschaft – Empfehlungen der Europäischen Malignen Hyperthermie Gruppe. Anasthesiol Intensivmed Notfallmed Schmerzther 2021;56:367–372.Google Scholar
Gallos, ID, Williams, HM, Price, MJ, et al. Uterotonic agents for preventing postpartum haemorrhage: a network meta-analysis. Cochrane Database Syst Rev 2018;4:Cd011689.Google Scholar
Ho, PT, Carvalho, B, Sun, EC, et al. Cost-benefit analysis of maintaining a fully stocked malignant hyperthermia cart versus an initial dantrolene treatment dose for maternity units. Anesthesiology 2018;129:249–259.Google Scholar
Heiderich, S, Thoben, C, Dennhardt, N, et al. Low anaesthetic waste gas concentrations in postanaesthesia care unit: a prospective observational study. Eur J Anaesthesiol 2018;35:534–538.CrossRefGoogle ScholarPubMed
Cork, RC, Vaughan, RW, Humphrey, LS. Precision and accuracy of intraoperative temperature monitoring. Anesth Analg 1983;62:211–214.Google Scholar
Larach, MG, Brandom, BW, Allen, GC, et al. Malignant hyperthermia deaths related to inadequate temperature monitoring, 2007–2012: a report from the North American malignant hyperthermia registry of the malignant hyperthermia association of the United States. Anesth Analg 2014;119:1359–1366.Google Scholar
Tran, DT, Newton, EK, Mount, VA, et al. Rocuronium versus succinylcholine for rapid sequence induction intubation. Cochrane Database Syst Rev 2015;2015:CD002788.Google Scholar
Duvaldestin, P, Kuizenga, K, Saldien, V, et al. A randomized, dose-response study of sugammadex given for the reversal of deep rocuronium- or vecuronium-induced neuromuscular blockade under sevoflurane anesthesia. Anesth Analg 2010;110: 74–82.Google Scholar
Richardson, MG, Raymond, BL. Sugammadex administration in pregnant women and in women of reproductive potential: a narrative review. Anesth Analg 2020;130:1628–1637.Google Scholar
Nestor, CC, Kearsley, R, Irwin, MG. Anaesthetic implications for a malignant hyperthermia-susceptible fetus. Anaesthesia 2021;76:1281–1282.Google Scholar
Griffiths, SK, Campbell, JP. Placental structure, function and drug transfer. CEACCP 2014;15:84–89.Google Scholar
Ueki, R, Tatara, T, Kariya, N, et al. Effect of decreased fetal perfusion on placental clearance of volatile anesthetics in a dual perfused human placental cotyledon model. J Anesth 2014;28:635–638.Google Scholar
Pacifici, GM, Nottoli, R. Placental transfer of drugs administered to the mother. Clin Pharmacokinet 1995;28:235–269.Google Scholar
Cherala, SR, Eddie, DN, Sechzer, PH. Placental transfer of succinylcholine causing transient respiratory depression in the newborn. Anaesth Intensive Care 1989;17:202–204.Google Scholar
Sewall, K, Flowerdew, RM, Bromberger, P. Severe muscular rigidity at birth: malignant hyperthermia syndrome? Can Anaesth Soc J 1980;27:279–282.Google Scholar
Hersch, PE, Matheson, KH. Anaesthetic considerations for a possible malignant hyperthermia susceptible fetus. Anaesthesia 1996;51:99.Google Scholar
Zucchi, R, Ronca-Testoni, S. The sarcoplasmic reticulum Ca2+ channel/ryanodine receptor: modulation by endogenous effectors, drugs and disease states. Pharmacol Rev 1997;49:1–51.Google Scholar
Diszházi, G, Magyar, Z, Mótyán, JA, et al. Dantrolene requires Mg(2+) and ATP to inhibit the ryanodine receptor. Mol Pharmacol 2019;96:401–407.Google Scholar
Driessen, JJ, Wuis, EW, Gielen, MJ. Prolonged vecuronium neuromuscular blockade in a patient receiving orally administered dantrolene. Anesthesiology 1985;62:523–524.Google Scholar
Shin, YK, Kim, YD, Collea, JV, et al. Effect of dantrolene sodium on contractility of isolated human uterine muscle. Int J Obstet Anesth 1995;4:197–200.Google Scholar
Weingarten, AE, Korsh, JI, Neuman, GG, et al. Postpartum uterine atony after intravenous dantrolene. Anesth Analg 1987;66:269–270.Google Scholar
Shime, J, Gare, D, Andrews, J, et al. Dantrolene in pregnancy: lack of adverse effects on the fetus and newborn infant. Am J Obstet Gynecol 1988;159:831–834.Google Scholar
Brandom, BW, Larach, MG, Chen, MS, et al. Complications associated with the administration of dantrolene 1987 to 2006: a report from the North American Malignant Hyperthermia Registry of the Malignant Hyperthermia Association of the United States. Anesth Analg 2011;112:1115–1123.Google Scholar
Craft, JB, Jr., Goldberg, NH, Lim, M, et al. Cardiovascular effects and placental passage of dantrolene in the maternal-fetal sheep model. Anesthesiology 1988;68:68–72.Google Scholar
Morison, DH. Placental transfer of dantrolene. Anesthesiology 1983;59:265.Google Scholar
Fricker, RM, Hoerauf, KH, Drewe, J, et al. Secretion of dantrolene into breast milk after acute therapy of a suspected malignant hyperthermia crisis during cesarean section. Anesthesiology 1998;89:1023–1025.Google Scholar

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