Paediatric Inborn Errors of Metabolism

Introduction

• Consider in all children who present with unexplained hypoglycaemia, acidosis, altered LOC, neurological symptoms or vomiting
• Initial therapy is almost always dextrose while awaiting further Ix
• Individually rare but as a group are not uncommon
• Majority will present already diagnosed in the era of newborn screening
• Consider if both a clinical and biochemical feature from the lists (see next slide)

Guide to identifying IEM

Groups of IEM

Investigations

• Must perform prior to therapy
• Baseline
  • FBC, Chem20, ammonia, CK
  • VBG
  • Serum ketones
• Hypoglycaemia (see next slides)
  • Serum insulin, cortisol, GH, ACTH, Free fatty acids, ketones, acylcarnitine profile (Guthrie card)
  • Urine organic and amino acids

Management

• Correction of altered homeostasis
  • Dextrose 5mL/kg 10% then infusion at maintenance rate 5-6mg/kg/min (up to 10mg/kg/min to suppress catabolism)
    • Higher rates may indicate hyperinsulinism
  • Correction of acidosis – sodium bicarbonate rarely used (sodium load and intracellular acidosis worsens)
• Reduction of toxic compound synthesis
  • Usually dietary modification
  • Increased caloric intake in the form of dextrose initially to combat catabolism is almost universal
  • Protein-containing calories (all infant formulas) should be avoided in undiagnosed IEM as most will have amino acid pathway defects
• Removal or enhancement of excretion of toxic compounds
  • Usually renal excretion, conjugated to carnitine
  • In some instances, dialysis/haemofiltration is the only option e.g. maple syrup urine disease and urea cycle disorders

Hypoglycaemia

• Definition: BSL <2.6mmol/L
• If diabetic, see diabetic emergencies powerpoint
• If not diabetic
  • Take critical blood samples (see next slide)
  • Hyperinsulinism is the most common cause under 2yo
    • Presence of ketonuria/ketonaemia makes this very unlikely
  • Accelerated starvation (ketotic hypoglycaemia) is the most common cause beyond infancy usually due to prolonged fast precipitated by mild illness
  • May be an early manifestation of sepsis, congenital heart disease, tumours, adrenal insufficiency or inborn error of metabolism

• History
  • Fasting/illness
  • History of toxin exposure e.g. alcohol, oral hypoglycaemics, alcohol, beta-blockers
  • Past history of hypoglycaemia, seizures
  • FHx of consanguinity, unexplained infant deaths or endocrine issues

• Critical blood samples
  • Glucose (capillary glucometers are unreliable at low readings)*
  • Ketones*
  • Free fatty acids*
  • Cortisol*
  • Insulin and C-peptide*
  • Lactate
  • Carnitine/acylcarnitine
  • Ammonia
  • Growth hormone
  • Amino acids
  • Electrolytes
  • LFT

• If conscious:
  • <1yo: Milk feed
  • >1yo: 
    • 15-30g oral glucose or 125-200mL soft drink/juice
    • Follow-up in 15-20min with single serve of complex carbohydrate
  • If unwell/vomiting, start IV N/saline + 5% dextrose at maintenance rate

• If unconscious
  • IV 2mL/kg 10% dextrose OR IM glucagon (0.5U if <25kg/8yo; 1U if >25kg/8yo)
• BSL remains <2.6 in 30 min
  • Give 2mL/kg bolus 10% dextrose and if second bolus required, increase maintenance to 10% dextrose

• Disposition
  • All patients with unknown cause require admission
  • Discuss the following with Endocrine/Metabolic
    • FTT (IEM), short stature (hypopituitarism, GH deficiency), macrosomia (Beckwith-Wiedemann)
    • Hepatomegaly (Beckwith-Wiedemann, glycogen storage, defects in gluconeogenesis, galactosaemia, fructose intolerance)
    • Midline facial defects (hypopituitarism)
    • Micropenis (GH deficiency)
    • Skin pigmentation (adrenal insufficiency)

Chronic presentations

• Some IEM present with chronic progressive degenerative manner (see next slide)

Metabolic encephalopathy

• 0.1% of babeis have IEM
• Acute presentations occur in neonatal/early infancy periods
• Symptoms often vague – poor feeding, lethargy, vomiting
• Hypoglycaemia – Organic acidurias, Reye’s syndrome, fat oxidation defects, MCAD
• Ketoacidosis – DM, organic acidurias
• Lactic acidosis – Mitochondrial disorders, respiratory chain disorders, pyruvate decarboxylase deficiency
• Hyperammonaemia (2-3x normal) – Reye’s, urea cycle defects, fat oxidation defects, organic acidurias, MCAD

Lovejoy Staging

Reye’s syndrome

• Rare disorder, exclusive to children
• Acute encephalopathy, cerebral oedema, fatty degeneration of viscera (liver)
• Typically intractable vomiting with encephalopathy
• Associate with aspirin and preceding varicella infection
• Diagnosis by hx + hyperammonaemia and LFT >2x ULN with normal bilirubin
• Hypoglycaemia seen in patients under 2yo
• Rx – Correct hypoglycaemia, neurological monitoring and ICP management

Last Updated on November 22, 2021 by Andrew Crofton