Multisystem Disorders

Question 1

What inheritance pattern is Wilson’s disease?

Answer 1

Autosomal recessive
Chrom 13,
ATP7B gene.

Question 2

What’s the diagnostic test for wilsons?

Answer 2

⬇️ serum caeruloplasmin
⬇️ serum copper
⬆️ urinary copper excretion
Increased copper in a liver biopsy

Question 3

What’s the treatment in Wilson’s disease?

Answer 3

Penicillamine Or trientine hydrochloride
(Both cheating compounds )

Zinc reduced absorption.

Liver transplant for end stage disease or fulminant hepatic failure.

Question 4

What is whipples disease?

Answer 4

Multi system disorder, caused by tropheryma whippelii infection.

Features: diarrhoea, wt loss, joint arthraligia, LNs, pleurisy and pericarditis, neuro (seizure, ophthalmoplegia, dementia.)

Dx: jejunal biopsy, with macrophages containing PAS (periodic acid-schiff) granules.

Question 5

What are the gene involved in haemochromatosis?

Answer 5

HFE gene mutations on chromosome 6. Autosomal recessive pattern.

Defect causes accumulation of iron.

Question 6

What are the features in haemochromatosis?

Answer 6

Early - fatigue, erectile dysfunction, arthalgia,

Late - skin hyperpigmentation , diabetes, liver, cardiomyopathy, arthritis. Pituitary : loss of libido, impotence,

Question 7

Blood test results in a person with haemochromatosis?

Answer 7

Liver biochem might be normal or Raised liver transminases,

Blood
Raised iron eg ferritin ⬆️⬆️⬆️ (>500)
Total iron binding capacity is reduced
Transferritin Saturation is >45% (normal <33%).

Question 8

What is sicca syndrome and what are its associations?

Answer 8

Dryness - of eyes, mouth etc.

Seen in Sjögren’s syndrome
Also seen in 70% of primary biliary cirrhosis pts.

To differentiate between the cause, do LFTs

Question 9

What is the pathophysiology in hereditary haemochromatosis?

Answer 9

Inappropriately increased iron absorption for the upper small intestine.

Question 10

Management of hereditary haemochromatosis?

Answer 10

Venesection 500ml twice weekly until stores normalise.

Then few times a year lifelong.

Question 11

What are the features of Wilson’s disease?

Answer 11

Liver cirrhosis
Basal ganglia : Parkinson’s, dementia
Eyes : kayser fleiser rings
Kidny - renal tubules

Question 12

What are the features of a1-antitrypsin deficiency?

Answer 12

Liver disease due to accumulation of abnormal protein.

Emphysema (loss of elastase (proeolytic enzyme not inhibited) )

Question 13

What is carcinoid syndrome? And it’s main features?

Answer 13

Neuroendocrine tumours, in epithelium of either lung or gut, stomach or liver (also liver mets).

Produce - serotonin, noradrenaline, dopamine, bradykinin and prostaglandins. Vasoactive substances are inactiviated by the liver therefore carcinoid syndrome only occurs when there is hepatic mets!

Serotonin - flushing
Diarrhoea
Bronchospasm

Question 14

Investigations for carcinoid syndrome?

Answer 14

Urinary 5- HIAA (>25mg per day)

Plasma chromogranin A Y

Question 15

What’s the treatment for carcinoid syndrome?

Answer 15

Somatostatin analogues (octreotide)