Hereditary Haemochromatosis Flashcards

1
Q

What is hereditary haemochromatosis?

A

Inherited disorder of iron metabolism in which increaed intestinal iron absorption leads to iron deposition in joints, the liver, heart, pancreas, pituitary, adrenals, and skin

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2
Q

Who does haemochromatosis most commonly affect?

A

Middle aged men

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3
Q

What gene is responsible for haemochromatosis?

A

HFE - commonest mutations are C282Y and H63D

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4
Q

What is the mechanism of damage in hereditary haemochromatosis?

A

HFE gene protein interacts with the transferrin receptor 1 -> Iron is taken up by the mucosal cells inappropriately, exceeding the binding capacity of transferrin.

Hepcidin, a protein synthesized in the liver, is central to the control of iron absorption; it is increased in iron deficiency states and decreased with iron overload. The mutations described above disrupt hepcidin expression, thereby internalizing ferroportin leading to uninhibited iron overload.

Hepatic expression of the hepcidin gene is decreased in HFE haemochromatosis, facilitating liver iron overload. Excess iron is then taken up by the liver and other tissues gradually over a long period. It seems likely that it is the iron itself that precipitates fibrosis.

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5
Q

What are clinical features of hereditary haemochromatosis?

A

Initially

  • Tiredness
  • Arthalgia
  • Decreased libido

Later

  • Slate-grey/bronze skin pigmentation
  • Signs of chronic liver disease
  • Endocrinopathies
  • Hepatomegaly
  • Cirrhosis
  • Dilated cardiomyopathy
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6
Q

What endocrinopathies can occur with hereditary haemochromatosis?

A
  • Diabetes mellitus - bronze diabetes
  • Hypogonadism
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7
Q

Why can diabetes occur in hereditary haemochromatosis?

A

Build up of iron in the pancreas -> bronze diabetes

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8
Q

Why does arthralgia/arthopathy occur in hereditary haemochromatosis?

A

Calcium pyrophosphate deposition in the joints - leading to chondrocalcinosis

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9
Q

Why does bronze pigmentation occur in hereditary haemochromatosis?

A

Melanin deposition

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10
Q

What is the classic traid of features seen in hereditary haemochromatosis?

A
  • Skin pigmentation
  • Diabetes mellitus
  • Hepatomegaly
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11
Q

What complications can occur from hereditary haemochromatosis?

A

Hepatocellular Carcinoma - if cirrhotic, 30% chance

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12
Q

What investigations would you consider doing in someone with suspected haemochromatosis?

A
  • Bloods - LFTs, Iron studies, glucose, HFE genetic analysis, testosterone, FSH, LH
  • MRI liver
  • Liver biopsy
  • Consider echocardiogram/ECG
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13
Q

What tests are included in iron studies?

A
  • Ferritin
  • Serum Iron
  • Transferrin/Total iron binding capacity (TIBC)
  • Transferrin saturations
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14
Q

What can cause ferritin to rise?

A

Acute phase protein

  • Liver disease
  • Malignancy
  • Inflammation
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15
Q

What does TIBC show?

A

Reflects the availibility of iron binding sites on transferrin

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16
Q

How is TIBC affected in Iron overload?

A

Decreased TIBC - the amount of transferrin that is available for iron to bind to is decreased

17
Q

What might iron studies show in someone with haemochromatosis?

A
  • Elevated serum iron
  • Decreased TIBC
  • Transferrin saturation > 45%
  • Elevated serum ferritin
18
Q

Why might you consider doing serum testosterone, FSH and LH in someone with suspected haemochromatosis?

A

May be low in those with hypogonadism

19
Q

Why might you do an echo/ECg in someone with suspected haemochromatosis?

A

Look for features of cardiomyopathy

20
Q

What might you find on liver biopsy in someone with haemochromatosis?

A

Iron loading and cirrhosis

21
Q

How would you manage someone with hereditary haemochromatosis?

A
  • Venesection - until ferritin < 50 ug/L
  • Low iron diet + food/drink which decreases iron absorption
  • Ensure vitamin preparations do not contain iron
  • Family screening
22
Q

What can cause secondary haemochromatosis?

A

Repeated transfusion

23
Q

What is the mode of inheritence of heredittary haemochromatosis?

A

Autosomal recessive inheritence

24
Q

What does serum total iron represent?

A

Measures the total amount of iron in the liquid portion of the blood, nearly all of which is bound to transferrin.

25
Q

What does measurement of serum ferritin represent?

A

Measures the level of ferritin, a protein made by almost all cells in response to increased iron to sequester it and prevent it causing toxic damage. The ferritin level reflects the total body iron.

It will be low when there is iron deficiency and high when there is an excess of iron in the body.

26
Q

What does a measurement of transferrin saturation represent?

A

Saturation = iron concentration/TIBC

Produces an estimate of how many of transferrin iron-binding sites are occupied; this is called the transferrin saturation. Under normal conditions, transferrin is typically one-third saturated with iron. This means that about two-thirds of its capacity is held in reserve