Inborn errors of metabolism

Question 1

What pathology occurs in urea cycle defects?

Answer 1

Accumulation of ammonia.

Question 2

What are the clinical effects of acute hyperammonia toxicity?

Answer 2

• lethargy
• poor feeding
• vomiting
• tachypnoea
• convulsions
• coma
• death

Question 3

What is porphyria?

Answer 3

A rare hereditary disease in which there is abnormal metabolism of the blood pigment haemoglobin. Porphyrins are required for the synthesis of haem. Individuals with porphyria lack one of the enzymes in this pathway. Porphyrins accumulate.

Question 4

What are the symptoms of acute porphyria?

Answer 4

• Severe abdominal pain
• Pain in your chest, legs or back
• Constipation or diarrhoea
• Vomiting
• Insomnia
• Heartbeat you can feel (palpitations)
• High blood pressure
• Anxiety or restlessness
• Seizures
• Mental changes
• Breathing problems
• Muscle pain/tingling/weakness/paralysis
• Red or brown urine

Question 5

What are the symptoms of photosensitive porphyria?

Answer 5

• Sensitivity to the sun/artificial light
• Sudden painful erythema and oedema
• Blisters that take weeks to heal
• Itching
• Fragile skin
• Increased hair growth
• Red or brown urine

Question 6

What is the difference between acute and photosensitive porphyria?

Answer 6

In acute there is a blockage at the beginning of the haem synthesis pathway - acute attacks occur only during times of stress when the body needs to synthesise more haem.
In photosensitive porphyria the pathway is blocked further down and the porphyrins build up more chronically.

Question 7

What might be the result of fatty acid synthesis defects?

Answer 7

Fatty acids are metabolised to ketones, used by the brain. In defects hypoketone hypoglycaemia occurs.

Question 8

What is androgen insensitivity syndrome?

Answer 8

• Healthy female phenotype normal breast development absent pubic hair, genetic male
• Partial defect results in ambiguous genitalia
• Presentation: primary amenorrhoea, infertility
• Usually need surgical resection of residual gonads

Question 9

What is homocytsinuria?

Answer 9

Defect of methionine metabolism homocysteine and cystathionine. Leads to an accumulation of homocysteine.

Symptoms may include:

Mental retardation
Marfinoid habitus
Ectopia lentis
Osteoporosis
Thromboembolism