Hereditary Haemochromatosis:Diagnosis and Management

Hereditary Haemochromatosis (HH) is a common autosomal recessive disorder occurring at a frequency of 1 in 200-250 among Anglo-Celtic Caucasian population in Australia. Most general practices, depending on the size, will have few to several of these patients . Most patients present with abnormal iron studies and or elevated liver tests and some with family history and can be managed at the general practice .

Fe Studies: Most patients present with elevated ferritin. For HIC requirement and the fact that fasting iron saturation of greater than 55% is more sensitive than ferritin, a fasting iron study should be ordered. If raised ferritin is demonstrated again, HIC requirement is then met for gene testing and a raised fasting iron saturation would further support the possibility of HH. Ferritin level can also be elevated with regular intake of even small amount of alcohol, in chronic inflammatory conditions, fatty liver and viral hepatitis.

Gene tests: Since the discovery of the HFE(HH gene) in chromosome 6 and availa- bility of blood tests to detect gene mutations(C282Y and H63D),the need for liver biopsies have rightfully declined.
Homozygous(two copies)C282Y is seen in greater than 90% of Australian HH. This with increased iron saturation and ferritin is almost diagnostic of HH without the history of regular moderate to heavy alcohol intake. This situation does not require liver biopsy unless patient exhibits features of liver failure.

Heterozygous (one copy) C282Y by itself rarely leads to iron overload unless combined with regular intake of alcohol. A liver biopsy in this situation may help to determine contribution from alcohol, fatty liver etc.
Compound heterozygous (one copy each of C282Y and H63D) could lead to iron overload in 3-5% of HH patients. Liver biopsy may determine any contribution from alcohol, fatty liver and viral hepatitis.

Homozygous (two copies) H63D: This situation is believed not to lead to HH. If liver tests are abnormal with abnormal iron studies, suspect contribution from alco- hol, fatty liver etc and consider a liver biopsy.
Heterozygous (one copy) H63D does not cause HH. If liver tests are also abnormal, then consider liver biopsy.

Liver Biopsy: has a prognostic value to determine if cirrhosis has already developed and useful if albumin is low and bilirubin and prothrombin times are elevated indicating progressive liver failure. While liver biopsy does not add to typical gene studies for HH, it does help to determine contribution from alcohol, fatty liver and viral hepatitis in cases with non-diagnostic gene mutation pattern as indicated in the previous section.

Treatment: Most patients find weekly venesections (500ml or less), as recommended by experts, difficult to comply with and is hard on the old veins. My prac- tice is to start with 2 weekly venesections for patients with ferritin>2000 and 3 weekly venesections for those with ferritin <2000. I do a set of iron studies and Hb after every 3rd venesection and dictated by the magnitude of improvement in these parameters, I space out intervals between venesections by 1-2 week each time. It usually takes between 9-16 months of venesection to attain normal iron studies and then maintenance venesection can be instituted at 3-4 monthly intervals. Blood Bank, S&N and QML provide venesection services.

Patients with cirrhosis and liver failure may need to be considered for liver trans- plantation. The Risk of liver cancer in HH patients with cirrhosis is 6% in males and 1.5% in females and need to be monitored with 3-6 monthly alfa-fetoprotein and 12 monthly ultrasound of the liver.

Family Screening: All first degree relatives should be screened for genetic mutations. Spouse of the index case should also be tested. If the spouse even has a single copy of a known mutation e.g., C282Y,then children should be tested probably after they have reached the age of 10 or older.

Future: Various other gene and their mutation and peptide products of these genes with relevance to HH has been identified. Hepcidin, produced in the liver, relates to hepatic iron stores. Transferrin receptor 2 protein is involved in iron transport. Ferroprotein I is involved in iron export. Ferritin H chain is involoved in iron storage. No doubt we shall hear more about the relevance of mutations in the genes of these peptides in near future.

Happy to provide references on request on this topic.


Investigation of small bowel: The last Frontier: Capsule Endoscopy or Push enteroscopy or both?

We are the only centre in Gold Coast and one of three centres in QLD to provide push enteroscopy for investigation of small bowel for gastroscopy and colonoscopy negative iron deficiency anaemia or overt GI bleeding, suspected small bowel Crohn’s, diarrhoea with wt loss etc. The push enteroscope is 2.3 metre long and is able to inspect upto 1.5 metre distal to the pylorus and can take biopsies, coagu- late bleeding vessels and remove polyps. Overall strike rate is 30-35%. It takes 20-30 minutes for the procedure. Patient requires sedation.

We also provide capsule endoscopy service. Radio-frequency signals transmitted by the swallowed capsule is recorded and analyzed for the entire 6 metre of small bowel . It is relatively non-invasive and takes 7-8 hr for the patient and 1-2 hours to report. Strike rate is 50-70%.It has poorer image quality than push enteroscope and can not biopsy, coagulate or remove polyps. Patient does not require sedation.

For gastroscopy and colonoscopy negative GI bleeding, either push enteroscopy followed by capsule endoscopy or capsule followed by push enteroscopy is recom- mended depending on individual clinical circumstances. Happy to discuss individ- ual cases. Currently, the two procedures are complementary.

The new double-balloon enteroscope by Fuji, yet to be officially available in Aus- tralia, views the entire small bowel and takes biopsies , coagulates bleeders and removes polyps and thus combines features of both capsule and push enteroscopy. However, It takes 2.5 hours or more to examine the entire small bowel and pa- tient requires sedation. It has the potential to replace both the capsule and the push enteroscope.

Happy to provide references on this topic on request.

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