Inborn Errors of Metabolism

Question 1

What are the different mechanisms that disease can occur?

Answer 1

• Accumulation of a toxin
• Energy deficiency
• Deficient production of essential metabolite/structural component

Question 2

What are the clinical effects of acute hyperammonaemia toxicity?

Answer 2

• Accumulation of a toxin
• Lethargy
• Poor feeding
• Vomiting
• Tachycardia
• Convulsions
• Coma
• Death

Question 3

What are possible signs of acute porphyria?

Answer 3

-Accumulation of a toxin
-severe abdominal pain
-pain in chest,legs,back
-constipation/diarrhoea
-insomnia
-vomiting
-palpitations
hypertension
-anxiety/restlessness
-mental changes
-seizures
-breathing problems
-red/brown urine
-Muscle pain/tingling/weakness

Question 4

What are possible signs of photosensitive porphyria?

Answer 4

• Accumulation of toxin
• Sensitivity to sunlight
• Sudden painful erythema & oedema
• itching
• blisters taking weeks to heal
• fragile skin
• red/brown urine
• increased hair growth

Question 5

How is haem produced and what problems can occur?

Answer 5

Alanine>PBG (acute porphyria)>uroporphrin> coproporphrin>protoporphrin (photosensitive porphyria)>haem

Question 6

What can defective receptors in females lead to and how does this present?

Answer 6

• Androgen insensitivity syndrome
• Female phenotype normal breast development, absent pubic hair, genetic male
• Partial defect=ambiguous genitalia
• Primary amenorrhoea, infertility
• Surgical resection
• Dependant on genetic variability & environment

Question 7

How are inborn errors diagnosed?

Answer 7

• pre-symptomatic screening = whole population/selected groups
• Investigation of symptomatic individuals= test body fluids, DNA analysis, histochemical, enzyme activity

Question 8

What are the clinical problems of homocystinuria?

Answer 8

• Homocysteine inhibited from becoming cysteine so builds in body w/methionine
• Mental retardation
• Marfinoid habitus
• Ectopia lentis
• Osteoporosis
• Thromboembolism

Question 9

What are the defects in classic organic acidaemias?

Answer 9

Defect in branched chain amino acid catabolism

Question 10

What pre-natal screening tests are available and what do they test for?

Answer 10

• Neural tube defects=maternal serum & amniotic fluid, ultrasound at 16weeks
• Down Syndrome=PAPA,HCG & nuchal translucency, maternal serum, inhibin,estriol, free fetal DNA