Inborn errors of metabolism

Inborn errors of metabolism

The common presentations of IEM are as follows:

• 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.

Investigations

• 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 sterile container with no preservatives.

• Subsequent investigation after discussion with expert: if 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 pathology laboratory for preservation.

Acute management

• Supportive.

• Stop all protein intake, including milk, and start 10% glucose IV infusion.

• Correct electrolyte/acid-base imbalance.

• Broad spectrum antibiotics in case crisis was precipitated by infection.

• Specific treatments after expert advice.

Prognosis

Depends on disease.