Haemochromatosis – At A Glance

Haemochromatosis is an autosomal recessive disease which is caused by an impairment in iron regulation leading to accumulation of iron in the parenchyma various organs.
It is the most common genetic disease among Caucasians.

Incidence – 1 in 300 to 500 individuals in Caucasians 

Inheritance

It is an autosomal recessive disease which occurs due to the mutation of HFE gene on both copies of chromosome 6.

Autosomal recessive inheritance

Secondary Causes

  • Thalassaemia with iron overload
  • Hemolytic anemia

Clinical presentation

  • Has an adult onset, usually in 30 – 50 years 
  • Most patients remain asymptomatic in early disease
  • Arthralgia is the most common problem that brings the patient to the doctor
  • Iron is deposited in the parenchyma of various organs  
  • Early presentation
    • Fatigue
    • Erectile dysfunction 
    • Arthralgia (Commonly affecting the hands)
  • Bronze pigmentation
  • Pancreatic involvement
    • Diabetes mellitus
  • Hepatic involvement
    • Hepatomegaly
    • Cirrhosis (Stigmata of CLCD)
  • Cardiac involvement
    • Restrictive cardiomyopathy
    • Heart failure
  • Pituitary involvement
    • Hypogonadism
    • Amenorrhoea
    • Impotency
  • Osteoporosis / osteopenia
  • Loss of hair, specially in the pubic region
  • Koilonychia

Investigations

  • Iron profile
    • Transferrin saturation
      • This is the earliest manifestations 
      • Transferrin saturation in haemachromatosis is > 60% in men and 50% in women (Normal transferrin saturation is about 25%)
      • If transferrin saturation is > 45% – Need further investigations to evaluate for haemachromatosis 
    • Serum ferritin
      • Serum ferritin is also elevated > 500 mcg/L
      • Less sensitive than transferrin saturation
    • Low TIBC
  • Gene testing for haemochromatosis 
  • Imaging studies
    • X-ray of joint
      • Most patients present with arthralgia 
      • Chondrocalcinosis is a characteristic feature
    • Chest X-Ray
      • Cardiomegaly
      • Increase pulmonary vascular markings
    • ECG – Features suggestive of restrictive type cardiomyopathy
    • MRI – Helps to identify organs with iron deposition 

Diagnostic Tests

  • Genetic testing for the C282Y mutation
  • Liver biopsy (Not done nowadays)
    • Hepatic iron index is calculated
    • Iron staining with Perls Prussian blue stain

Screening

  • Not done as a global protocol
  • High risk groups are subjected for screening test
  • Best screening test – Transferrin saturation 
  • If transferrin saturation > 45% – Further investigations are done to confirm the diagnosis

Treatment

The aim is remove the deposited iron in organs, so that it would not cause irreversible parenchymal damage and prevent future accumulation of iron in organs. 
Early diagnosis carries very good prognosis and can have a normal life span if organs are not permanently damaged at the time of diagnosis. 

Cardiomyopathy, skin pigmentation, hepatomelagaly or elevated LFTs without cirrhosis is considered reversible and the rest are irreversible (Diabetes, hypogonadism, arthropathy)

  • Phlebotomy – Best treatment modality
    • This is a life long treatment and the frequency depends on the patient’s serum ferritin levels 
    • This is done to remove the excess amount of iron from the body
    • Initially phlebotomy is performed weekly where blood is withdrawn at 7 mL/kg per phlebotomy (Maximum : 550 mL per phlebotomy)
      Weekly phlebotomy is continued till serum ferritin level reaches the upper limit of normal (300 mcg/L in males & 200 mcg/L in females)
    • Thereafter plebotomy is performed at a frequency of 2 – 4 months, till serum ferritin become < 50 mcg/mL
    • Continue life long phlebotomy depending on the level of serum ferritin
  • Iron chelation
    • Done in patients who cannot remove phlebotomy 
    • Deferasirox is an oral iron chelating agent
    • Deferasirox should be dissolved in water or milk and should be taken in an empty stomach
  • Dietary modification
    • Avoid excess iron containing food – Red meat, liver, spinach 
    • Avoid multivitamins, iron supplements, vitamin C supplements 
    • Avoid citric food (Lemon, lime, etc)
    • Tea (tannates) after meals reduce the absorption of iron
  • Treatment of complications
    • Severe arthropathy – May warrant Surgical arthroplasty
    • Control of diabetes mellitus

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Бети Маринова
Бети Маринова
1 year ago

Wanted to learn more about phlebotomy and you have explained it very clearly, thank you!