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Approach to Inborn Errors of Metabolism. Dr Yaser A. Mohammad. Why did you choose this topic ?. 2 Cases. 2 yrs old boy KCO Ethylmalonic Aciduria. Presenting with bronchopneumonia & Metabolic crisis. Drowsy, acidotic breathing, tachycardic , BP & SPo2 maintained with O2.

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Approach to Inborn Errors of Metabolism

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Approach to inborn errors of metabolism

Approach to Inborn Errors of Metabolism

Dr Yaser A. Mohammad

Approach to inborn errors of metabolism

Why did you choose this topic ?

2 cases

2 Cases

  • 2 yrs old boy KCO Ethylmalonic Aciduria.

  • Presenting with bronchopneumonia & Metabolic crisis.

  • Drowsy, acidotic breathing, tachycardic , BP & SPo2 maintained with O2.

  • BGA PH: 7.15 CO2: 2 HCO3: 12 BE: -15

    RBS : 8 Lactate: 6.5 Ammonia : 40

Approach to inborn errors of metabolism

  • 5 yrs old boy KCO Arginosuccinic Aciduria.

  • Presenting sleepy & vomiting after taking an overdose of his antiepileptics(phenobarbitone & Keppra) & missing 2-3 doses of his metabolic medicine.

  • Drowsy GCS 11-12 , HR 70, BP & SPo2 maintained in R.A.

  • BGA PH 7.43 PC02: 5 HCO3: 23 BE : -1.5

    K : 1.9 RBS : 8 Ammonia 246



  • Brief description of types of IEM that have an acute presentation.

  • Approach to metabolic emergencies.

  • Diagnostic clues

  • Quiz

Organic acid disorders

Organic Acid Disorders

- Results from enzyme deficiencies in the pathway of Amino acids degradation.

  • Presentation with acidosis, hypoglycaemia lactic acidosis & hyperammonaemia. Ketosis may also occur.

  • Analysis of the urine for Organic Acids is the mainsty of the Dx.

  • E.g. Methylmalonic, Ethylmalonic & propionic Acidaemia.

  • Rx low protein diet, avoid catabolic state; high carbs feeds during illness & carnitine.

Urea cycle defect

Urea Cycle Defect

  • Defect in the metabolism of Ammonia in the Urea Cycle, so high Ammonia.

  • Presentation : poor feeding, lethargy, convulsion, coma & Resp. alkalosis.

  • Difficult to Dx due to lack of biochemical abnormality apart of hyperammonaemia.

  • Treated as sepsis initially.

  • Dx with raised Plasma Amino Acids.

  • E.g. Ornithine transcarbomylase, Arginosuccinicaciduria.

  • Rx low protein diet, Na benzoate, phenylbutyrate & arginine. Avoid catabolic state.

Fatty acid oxidation defect

Fatty acid oxidation defect

  • FA oxidised in skeletal muscle, heart & liver.

  • 4 enzymes inolved (Chain Acyl-CoA Dehydrogenase).


  • Presentation: Non-ketotichypoglycaemia, lethargy, siezures, myoglubiuria, mucsle weakness & cardiomyopathy.

  • Dx: Reye like illness ( hypoglycaemia, raised ALT & AST , no ketosis). Hyperammonaemia.

  • Dx: Acylcarnitine profile by tandem mass spectrometry. Urine O.A & skin fibroblasts enzyme assay.

  • Rx prevention of fasting stress & carnitine.

Mitochondrial do

Mitochondrial DO

  • Have their own DNA & are derived from the ovum, so all mtDNA DO are mternally inherited.

  • Presentation: weakness, abnormal tone, opthalmoplegia, seizures, cadiomyopathy, liver failure. Lactic acidosis with normal glucose.

  • Dx enzyme analysis of fibroblast, muscle or liver biopsy.

  • E.g MELAS ( Mitochondrial Encephalopathy, Lactic acidosis & Stroke like episodes).

    MERRF ( Myoclonic Epilepsy with ragged red fibres)

Carbohydrate metabolism do

Carbohydrate metabolism DO

  • Galactosaemia; GAL-1-PUT. Accumulatiomof GAL-1 phosphate damages liver , brain & kidney

  • Presentation: vomiting, hypoglycaemia, irritibilitysiezures, jaundice, hepatomegaly & cataracts.E.coli sepsis.

  • Dx enzyme assay in RBC. Urine: non-glucose reducing substance.

  • Rx Lactose & galactose free diet.

Carbohydrate metabolism do1

Carbohydrate metabolism DO

  • Glycogen Storage disease

  • Threre are several enzyme deficiencies that leads to glycogen accumulation.

  • Primarly affect liver, muscle or both.

  • Presentation : hypoglycaemia, hepatomegaly, lactic acidosis, weakness & cardiomyopathy.

  • Dx : enzyme assay of blood, liver or muscle biopsy.

  • Rx : avoidance of fasting, continuous overnight feeds & uncooked corn starch.

How iem present

How IEM present?

  • Non-specific symptoms

  • Attributed to infection or sepsis

  • Routine blood tests could be normal

  • Suspect when lack of improvement with standard therapy.

  • Neontal screening.

Metabolic crisis

Metabolic crisis

  • Metabolic crisis occur when there is build up of toxic metabolites. Triggers factors that increase catabolism:

  • Infection

  • Fasting

  • trauma

  • Surgery

  • Increase consumption of protein.

Clinical presentation

Clinical presentation

  • An acute presentation with multisystem involvement is strongly suggestive of an IEM. It can include:

    - Vomiting and anorexia or failure to feed.

    - Lethargy that can progress to coma.

    - Seizures, particularly intractable.

    - Rapid, deep breathing that can progress to apnea.

    - Hypothermia (related to illness, not specific to a particular metabolic pathway).

Approach to inborn errors of metabolism

  • In one review of 53 patients who presented to an emergency department and were subsequently diagnosed with an IEM:-

  • 85 % had neurologic signs or symptoms.

  • 58 % had gastrointestinal signs or symptoms.

  • 51 % had both neurologic and gastrointestinal signs and/or symptoms.



  • Glucose

  • ABG

  • CBC, U &E, LFT

  • Urine: color, odor, dipstick & ketones

  • Ammonia

  • Lactate

Diagnostic clues

Diagnostic clues

Diagnostic clues1

Diagnostic clues

Diagnostic clues2

Diagnostic clues

Immediate mx

Immediate Mx

  • Fluid resuscitation

  • Treatment of hypogycaemia

  • Ventilation support

  • HCO3 for correction of acidosis ( rapid correction have adverse effect on CNS).

  • Empiric IV antibiotic

  • Stop oral feeding pending Dx.

  • Avoid catabolism by administration of IV D10% with electrolyte. 8-10mg/kg/min.

Provision of co factors

Provision of co-factors:

  • Pyridoxine: 100mg iv for uncontrolled seizures.

  • Cobalmine: (Vit B 12 1mg im) metabolic acidosis & suspected organic acidaemia.

  • Carnitine: (100 mg/kg per day in three divided doses either orally or IV) may be useful in patients with organic acidemias, fatty acid oxidation disordersorcarnitinedefeciency.

  • Biotin: 10 mg for neonate with recurrent seizures

Approach to inborn errors of metabolism




  • Optimal outcome of IEM depends on early recognition, diagnosis, treatment of metabolic decompensation.

  • Symptoms are non-specific

  • Initial investigation could give a clue to diagnosis pending more detailed ones.

  • management of metabolic decompensation must be initiated promptly to avoid long term sequele.



  • Inborn Errors of Metabolism overview & specific disorders by Paul Levy. Pediatrics in review vol 30. No. 4 April 2009.

  • Inborn errors of metabolism : metabolic emergencies. Uptodate, pediatrics. Reid Sutton.

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