Testing for HH

An iron studies profile can assist in an initial diagnosis. This test includes: an iron count; transferrin saturation (normal less than 45% in women and 50% in men); and serum ferritin (normal less than 200mg/L). If high levels are confirmed, other tests may be necessary to assess organ damage, such as a genetic test and liver biopsy.

Transferrin saturation (TS):
This is calculated by dividing the Serum Iron level by the total iron binding capacity (TIBC). A normal average is 30%. If it is over 55% in men and 50% in women, HH is very likely.

Serum Ferritin: Reflects level of iron stores in the body. If it is over the upper limit of 300ug/l in men and 200ug/l in women this is further evidence of HH – a raised TS with a normal SeFn does not rule out HH.
Biochemical testing is limited by the fact that serum iron and ferritin levels may be affected by factors such as liver disease and inflammation, while DNA testing provides a reliable diagnostic tool. To date, more than three genes underlying inherited iron overload have been identified.

​African-specific mutations identified locally have been detected in Black patients referred for genetic testing and might contribute to iron overload in this population. It is extremely important to detect a genetic predisposition for HH at an early age, before irreversible damage to cardiac, hepatic and endocrine tissue occurs.

Genetic testing and in particular the PCR HAEMOCHROMATOSIS test can be carried out in South Africa through LANCET LABORATORIES on referral by a doctor. It is important that the blood tests be done after a period of fasting. It is also important to remember that ferritin is an acute phase reactant, which means it is affected by any kind of inflammatory process. Inflammation can occur as a result of taking certain medications, or can be due to the presence of chronic or current disease/illness. Professional diagnosis by a specialist who is familiar with Haemochromatosis is therefore vital.

The objective of the guidelines provided below is to assist health care providers in the effective identification of individuals with Haemochromatosis or a genetic predisposition for this condition, in order to prevent the many common conditions that may be caused by iron overload resulting in organ damage.

OPTION 1 Transferrin saturation 50%, ferritin 250 mg/L: Test the HFE-gene Mutations H63D, S65C and C282Y account for the condition in more than 80% of affected individuals.
Those who inherit a mutation from both parents are homozygous and are likely to develop the condition, whereas those who inherit from one parent are carriers who may show a lesser increase in iron absorption. The presence of a single mutation – carrier frequency of C282Y is 1/6 – is associated with an increased risk of heart disease and cancer in the general population.
Molecular diagnosis of hereditary haemochromatosis –Identify an affected person and save a family” –
Editorial: S Afr Med J 1999; 89: 263-264.

OPTION 2 Patients with iron overload who test negative for mutations in the HFE gene may choose to proceed with testing of two newly identified genes. Mutation-negative patients with abnormal iron status: test new genes, including TFR-2 & SLC11A3. Although HFE gene mutations H63D, S65C and C282Y account for HH in more than 80% of affected South Africans, a large proportion of patient referrals test negative for these mutations or carry only a single copy of one of these mutations. Iron overload in individuals without mutations in the HFE gene may be caused by defects in newly identified genes such as the -2 (TFR-2) and ferroportin (SLC11A3) genes.
​Genetic counselling and, if necessary, a simple and comprehensive mutation detection test for mutations in the HFE gene is available.