From the Guidelines
The specificity of Transferrin Saturation (TSAT) for diagnosing Hereditary Hemochromatosis (HH) is approximately 90-95% [ 1 ], meaning that about 5-10% of individuals with elevated TSAT may not have hemochromatosis.
Key Points:
- A TSAT level above 45% in men and above 35% in women should be further evaluated with genetic testing for HFE mutations, liver function tests, and serum ferritin levels to confirm the diagnosis of hemochromatosis [ 1 ].
- The sensitivity and specificity of serum ferritin level and TSAT can vary depending on the cutoff values used, with lower cutoffs being more sensitive but less specific [ 1 ].
- The diagnostic cutoff levels of 500 µg/L for serum ferritin and 62% for TSAT have been shown to identify a subgroup of patients with hereditary hemochromatosis [ 1 ].
- The prevalence of hereditary hemochromatosis is estimated to be around 3-5 people per 1000 in the general population, with a higher prevalence among non-Hispanic white persons [ 1 ].
From the Research
Transferrin Saturation (TSAT) Specificity for Diagnosing Hereditary Hemochromatosis (HH)
- The specificity of TSAT for diagnosing HH has been evaluated in several studies 2, 3, 4, 5, 6.
- A study published in 1998 found that a transferrin saturation threshold of 45% identified 98% of homozygotes without misidentifying any normal individuals 2.
- Another study published in 2002 found that the optimum threshold for transferrin saturation was 43%, giving a sensitivity of 0.88 and specificity of 0.95 3.
- A study published in 2003 found that a TSAT cut off >45% provided a good combination of sensitivity and specificity for detecting C282Y homozygosity, but a cut off >60% provided the best combination 6.
- However, a study published in 2007 found that the within-person biological variability of TSAT limits its usefulness as an initial screening test for expressing C282Y homozygotes, with 33% of C282Y homozygotes being missed at a TSAT cut point of 45% for women and 50% for men 5.
Comparison of TSAT with Other Tests
- A study published in 2002 found that unsaturated iron binding capacity (UIBC) has equal reliability to TSAT in detecting HFE hemochromatosis, with a sensitivity of 0.91 and specificity of 0.95 3.
- Another study published in 1998 found that serum ferritin has a higher sensitivity than TSAT in detecting iron overload in C282Y homozygotes, with a sensitivity of 96% in men and 97% in women 4.
Clinical Implications
- The use of TSAT as a screening test for HH has been advocated due to its high specificity and sensitivity 2, 3, 6.
- However, the within-person biological variability of TSAT limits its usefulness as an initial screening test, and a combination of TSAT and other tests such as UIBC and serum ferritin may be more effective in detecting HH 5.