This document provides guidelines for the emergency treatment of inborn errors of metabolism (IEM). It outlines that IEM should be considered for acute presentations with non-specific symptoms like encephalopathy, seizures, or multi-system involvement. Initial treatment should start immediately and includes stopping feeding, supportive care, investigating with blood and urine tests, treating abnormalities like hypoglycemia and hyperammonemia, and providing calories to prevent catabolism while consulting metabolic specialists. Ongoing care involves correcting ongoing issues, providing adequate nutrition and calories, and transferring if a higher level of care is needed. The guidelines stress the importance of early treatment without waiting for a diagnosis to prevent permanent damage from IEM emergencies.

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.  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.
Introduction

5.  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
Introduction

6.  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.
Introduction

7. When To Consider …… IEM ?

8. Acute presentations where a metabolic
disorder should be considered
Biochemical
changes
Clinical manifestations
Most common :
 Hyperammonaemia,
 Acid-base imbalance
 Hypoglycemia
 Hepatic dysfunction
•Progressive encephalopathy without clear evidence
• Newborn with poor feeding, weak suck or hypotonia.
•Recurrent seizures
•Presumed sepsis with poor response to treatment
•Unexplained shock or cardiac failure
•Rapid, deep breathing +/- progression to apnea
•Hepatomegaly or splenomegaly
•Any acute presentation with multisystem involvement

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: consider the
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
First line investigations (collection as per local hospital
protocol)
CSF Only if LP is taken
for infection screen
Urine
Blood
 Glucose & Lactate (take
plasma sample
immediately before LP)
 Amino acids – glycine,
threonine, serine (take
plasma sample at the
same time as the LP)
• ketones, glucose,
pH
• Metabolic screen
(including amino
acids and organic
acids)
• Venous or capillary blood
gas
• Glucose (point of care
testing appropriate)
• Serum lactate (venous
sample)
• Serum ammonia (transfer
sample urgently)
• Other tests as clinically
indicated eg FBC, UEC,

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:

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

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

18. c) Treatment of hyperammonemia:

19. c) Treatment of hyperammonemia:

24. Nutrition
 Aim to give 100kcal/kg/day, if possible as 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
1. British Inherited Metabolic Disease Group: Undiagnosed hyperammonaemia. Diagnosis and immediate
management, 2008. Accessed January 2019 at http://www.bimdg.org.uk/site/index.asp
2. 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
3. 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/
4. 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
5. SC(NHS)FT Drugs for the Treatment of Inborn Metabolic Diseases 2019 (CAEC Reg ID 807)
6. SC(NHS)FT Investigation of Suspected Inherited Metabolic Disorders 2019 (CAEC ID 1067)
7. SC(NHS)FT Unexplained hypoglycaemia – guide to emergency investigations and management (CAEC
ID 293)
8. Saudubray J-M, Baumgartner M, Walter J (Eds.). Inborn Metabolic Diseases Diagnosis and Treatment 6th
edition; 2016.