Inborn Errors of Metabolism

Question 1

IEM

Answer 1

Most autosomal recessive

Error in metabolism - disrupt normal function by either lack of end product or accumulation of toxic chemical

Question 2

IEM - can present in a multitude of ways at any age, most present in early childhood

Answer 2

Raised anion gap
Significant metabolic acidosis
Unexplained resp alkalosis
Hypoglycaemia 
Cardiac failure / cardiomyopathy 
Hepatomegaly / hepatosplenomegaly / liver dysfunction
Unexplained drowsiness, coma or irritability 
Early onset seizures
Dysmorphic features
Developmental regression 
Sudden unexplained death

Question 3

Hx

Answer 3

Normal paeds Hx

Plus: FH of IEM, FH of sudden unexplained deaths, consanguinity

IF IEM SUSPECTED CONTACT SPECIALIST METABOLIC CENTRE FOR ADVICE

Question 4

Hyperammonaemia

Answer 4

Toxic chemical derived from the break down of proteins

Should be measured if encephalopathy (irritability and reduced LOC), resp alkalosis, recurrent vomiting, unexplained seizures, unexplained severe illness in a baby or child

Management: stop feeds + 10% dextrose and IV ammonia scavenging meds + arginine

Question 5

Hypoglycaemia

Answer 5

< 2.6

Common in first day of life in infants who are pre term / growth restricted / ill

After this check in child who - appears seriously ill, prolonged seizure, developed altered state of consciousness

Question 6

Neonatal Jaundice

Answer 6

50% of all newborn infants become visibly jaundiced

May be a sign of another disorder
Unconjugated bilirubin can be deposited in the basal ganglia and brainstem nuclei causing Kernicterus

Question 7

Kernicterus

Answer 7

Encephalopathy
Occurs when level of uncong bili exceeds the albumin binding capacity of bilirubin

Lethargy, poor feeding, irritability, seizures, coma

Can be cause of brain damage in children with rhesus haemolytic disease - rhesus D prophylaxis to all rhesus negative mothers has made this rare

Question 8

Jaundice < 24 h

Answer 8

Always pathological
Usually results from haemolysis - rhesus / ABO incompatability, G6PD deficiency, spherocytosis

Important to recognise during newborn examination

Question 9

Jaundice 24h - 2 weeks

Answer 9

Very common
Tx: phytotherapy - converts ungonjugated bili into water soluble pigment excreted in urine

Physiological - occurs as the neonate is adapting to the transition from foetal life, only diagnosed after other causes have been considered

Breast milk jaundice - more common and more prolonged, unconjugated bilirubinaemia

Question 10

Overview

Answer 10

Errors in the way chemicals are built up - lack of product or accumulation of a toxic chemical
Often affects the brain - neuro problems
Usually autosomal recessive 
Often treatable, usually by diet
Prenatal diagnosis possible