Inborn errors of metabolism
Perturbation of these metabolic pathways results in a spectrum of clinical findings affecting multiple organ systems.
Inborn errors of metabolism (IEM) are genetic conditions that block metabolic pathways involved in the breakdown of nutrients and the generation of energy. Perturbation of these metabolic pathways results in a spectrum of clinical findings affecting multiple organ systems.
The common presentations of IEM
- Encephalopathy without metabolic acidosis: e.g. pyridoxine-dependent seizures, urea cycle enzyme defects;
- Encephalopathy with metabolic acidosis: e.g. organic acidurias;
- Hepatic failure: e.g. galactosaemia;
- Non-immune hydrops: can be haematological, e.g.β-thalassaemia, or due to lysosomal storage disorder, e.g. Gaucher disease;
- Significant dysmorphism: these can be divided into lysosomal disorders,e.g. mucopolysaccharidosis; peroxisomal disorders, e.g. Zellweger syndrome; mitochondrial disorders; biosynthetic defects, e.g. albinism; receptor defects, e.g. pseudo-hypoparathyroidism;
- Other: non-specific illness; severe hypotonia; resistant hypoglycaemia; cataracts; odours; cardiomyopathy; severe diarrhoea.
- Initial: blood for U&E, SBR, gas analysis, glucose, Ca2+, Hb, ammonia, and anion gap (normal range 12–16mmol/L). Urine for ketones and reducing substances.
- ‘Metabolic screen’ (for amino acid and organic acid analysis): take and save blood in heparinized (1–2mL) and EDTA (3–5mL) tubes and save urine (5–10mL) in a sterile container with no preservatives.
- Subsequent investigation after discussion with an expert: if the child dies prior to diagnosis, seek permission to take:
- further blood for storage (clotted and heparinized);
- skin biopsy placed in sterile saline;
- liver and muscle biopsy;
- send immediately to a pathology laboratory for preservation.
- Stop all protein intake, including milk, and start a 10% glucose IV infusion.
- Correct electrolyte/acid-base imbalance.
- Broad-spectrum antibiotics in case the crisis were precipitated by infection.
- Specific treatments after expert advice.
Depends on the disease.