Emergency Treatment of Acutely Presenting Inborn Errors of Metabolism

1. Guidelines for the Emergency Treatment of Inborn Errors of Metabolism Dr/ Tahany Nabil Mahmoud, MD • Consultant of Pediatrics & Neonatology • Toukh Central Hospital, Ministry of Health, Egypt • 2023

2. Introduction • When To Consider …… IEM • Acute presentations of IEM • Guidelines • Investigations • Treatment • Special considerations • Take Home Message • References

3. Introduction • Metabolic disorders are a large group of inherited conditions resulting from a block (partial or complete) to a pathway in the body’s metabolism, or defects in the transport of substances.

5. Introduction • Although IEM are individually rare, collectively they represent an important cause of childhood morbidity and mortality. • Newborn screening will diagnose many but not all metabolic disorders and a newborn may also become unwell before results are available. • Many inborn errors are stable for long period but still have episodes of acute illness.

6. Introduction • Unfortunately, the early symptoms and signs of acutely presented IEM are non-specific. • Therefore, treatment should start immediately and does not wait for a diagnosis to prevent permanent damage.

7. When To Consider …… IEM ?

8. Acute presentations where a metabolic disorder should be considered

9. Guidelines Initial general management in all patients suspected of presenting acutely with an inherited metabolic disorders

10. Initial Investigations • Serves as a guide only: so consult the metabolic team with abnormal results • During Interpretation of Investigations: considerthe period of fasting, hydration status, stage of illness and what fluids or other management have already been started • A normal newborn screen, although possibly reassuring, does not rule out the possibility of an IEM. • These findings are Non-specific and may be present in an unwell child without a metabolic disorder • Careful collection and handling of blood, urine and CSF samples is important, but should not delay management of the unwell child

11. Investigations

13. Treatment • The initial management should be started immediately but the biochemical results can guide subsequent treatment. • Confirmation of the diagnosis by molecular genetic testing is useful, but results are rarely available during the acute illness. • Early consultation with metabolic team: • As soon as a metabolic disorder is suspected • For children who present with a known metabolic condition.

16. 1) Stop feeding 2) Supportive therapy : • ABC  Secure air way +Ensure goodhydration & tissue perfusion (Glucose 10% + NaCL 0.9%) • Treat underlying or precipitating illnesseg., sepsis, gastroenteritis • Prevent catabolism: high calories (Dextrose 10%) Check blood sugar hourly. If plasma glucose > 14mmol/L (hyperglycemia) • Generally start IV insulin infusion rather than decrease glucose. • In lactic acidosis Reduce glucose infusion? as insulin can aggravate acidosis

17. 3) Specific therapy: • Treat hypoglycemia: IV Dextrose containing fluids • Correction of metabolic acidosis:

18. c) Treatment of hyperammonemia:

19. c) Treatment of hyperammonemia:

24. Nutrition • Aim to give 100kcal/kg/day, if possibleas enteral feed(even during hemofiltration). • Parenteral nutrition can be given initially as intralipid (up to 4g/kg/day, 40kcal/kg/day) and 10% glucose IV (40kcal/kg/day at 100ml/kg/day). • It may be difficult to achieve a total of 100kcal/kg/day with IV therapy alone.

25. Nutrition • Once ammonia and / or pH are normalized and stable start • Protein, 0.5 g/kg/day only • Lipid, 20% of total energy intake • Carbohydrate to provide at least the minimum necessary energy intake) • Patients with inherited metabolic disease should not have protein free nutrition for longer than 48 hours, as this can lead to protein catabolism and exacerbate decompensation • Monitor ammonia and / or blood gas twice daily as protein increased.

26. 6) Nutrition

27. Special Considerations • Preoperative: • Always be planned early with the metabolic team • Avoid prolonged fasting with provision of sufficient calories (using IV glucose-containing solutions) to prevent catabolism • Transfer when: A child requiring care beyond the comfort level of the hospital

28. Take Home Message

29. Take Home Message • Acute metabolic emergencies in neonates represent a challenge to the medical staff. • Many inborn errors are stable for long periods but still have episodes of acute illness. • IEM that present acutely have non- specific symptoms and the delayed treatment will worsen the outcome. • A normal newborn screen, although possibly reassuring, does not rule out the possibility of an IEM.

30. Take Home Message • Management is a Multidisciplinary care and should start immediately and does not wait for a final diagnosis. • The gold-standard treatment include; high index of suspicion of IEM, correcting abnormalities, providing calories/reducing catabolism/ providing cofactors and specific measures addressing the disturbed metabolic process . • Don’t forget the basics ( i.e, treatment of precipitating factors e.g., sepsis) to prevent acute decompensation

31. References • British Inherited Metabolic Disease Group: Undiagnosed hyperammonaemia. Diagnosis and immediate management, 2008. Accessed January 2019 at http://www.bimdg.org.uk/site/index.asp • CAEC Registration Identifier: 1245 Sheffield Children’s (NHS) Foundation Trust;Guideline for the Emergency Treatment of Inborn Errors Mark Sharrard Review date: August 2022. Page 7 of 9 • Jeanmonod R, Asuka E, Jeanmonod D. Inborn Errors of Metabolism. [Updated 2023 Jul 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459183/ • North West & North Wales Paediatric Transport Service. Guidelines for the Management of Neonatal and Paediatric Hyperammonaemia, 2018. Accessed online at http://www.nwts.nhs.uk/_file/iKiUZIP7gM_290986.pdf • SC(NHS)FT Drugs for the Treatment of Inborn Metabolic Diseases 2019 (CAEC Reg ID 807) • SC(NHS)FT Investigation of Suspected Inherited Metabolic Disorders 2019 (CAEC ID 1067) • SC(NHS)FT Unexplained hypoglycaemia – guide to emergency investigations and management (CAEC ID 293) • Saudubray J-M, Baumgartner M, Walter J (Eds.). Inborn Metabolic Diseases Diagnosis and Treatment 6th edition; 2016. • The NEWT Guidelines. October 2016 http://access.newtguidelines.com/C/Carglumic_acid.html