Sample Stability:
- 1 week at 4 o C
50-80%
Glycosylated ferritin (GF) can be useful in differentiating causes of high ferritin.
A. Very low levels (< 20%) especially in those with significantly elevated ferritin (>10, 000ug/L) can be suggestive of Adult onset Still's disease (AOSH), haemophagocytic lymphohistocytosis (HLH) or drug induced hypersensitivity syndrome [1].
B. Lower levels of glycosylated ferritin (between 20-55%) can be associated with Hereditary Hyperferritinaemia Cataract Syndrome (HHCS) which is a genetic condition affecting the iron regulation element leading to increased L-ferritin synthesis, unregulated by iron reserve. This condition is not associated with raised transferrin saturation or soluble transferrin receptor [2].
C. Persistently high Glycosylated ferritin (> 90%) level can be found in Benign hyperferritinaemia (BH) which is linked to a genetic variant of the L-ferritin chain. In this condition, the transferrin saturation is also not raised and there is no iron overload nor cataract [3].
D. In patients with hepatocellular injury, metabolic syndrome, renal failure, infections, malignancy and hereditary haemochromatosis, their glycosylated ferritin generally falls within the 20-80% range. Other than to aid the diagnosis of the 2 hereditary conditions HHCS and BH, testing glycosylated ferritin for mild to moderately raised ferritin is usually not helpful in differentiating the above mentioned acquired conditions[4].
E. For diagnosis of Adult onset Still's disease:
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The combination of a GF <= 20% and plasma ferritin more than 5 times the upper reference limit had been reported in one study with a sensitivity of 43.2% and specificity of 92.9% for Adult Onset Still's Disease [5].
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Glycosylated ferritin of <20% is a major criterion in the Fautrel classification criteria for Adults onset Stills disease. This criterion carries a sensitivity of 87% and specificity of 97.8%.
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Minor criteria include: maculopapular rash; leukocyte > 10,000/mm 3
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Major criteria include: Spiking fever 39 o C; Arthalgia, Transient erythema, pharyngitis, polymorphonuclear percentage > 80% and glycosylated ferritin < 20%.[6]
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4 Major Criteria OR 3 Major with 2 Minor
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While total ferritin levels may fall, glycoslyated ferritin remains low in both the active and remission phase of ASOD [7].
References:
- Ben M'rad M, Leclerc-Mercier S, Blanche P, Franck N, Rozenberg F, Fulla Y, et al. Drug-induced hypersensitivity syndrome: clinical and biologic disease patterns in 24 patients . Medicine (Baltimore) 2009 88:131-140.
- Cazzola M, Bergamaschi G, Tonon L, Arbustini E, Grasso M, Vercesi E, et al. Hereditary Hyperferritinemia-Cataract Syndrome: Relationship Between Phenotypes and Specific Mutations in the Iron-Responsive Element of Ferritin Light-Chain mRNA . Blood 1997 90:814-821.
- Thurlow V, Vadher B, Bomford A, DeLord C, Kannengiesser C, Beaumont C, et al. Two novel mutations in the L ferritin coding sequence associated with benign hyperferritinaemia unmasked by glycosylated ferritin assay . Ann Clin Biochem 2012 49:302-5.
- Chapman RW, Gorman A, Laulicht M, Hussain MA, Sherlock S, Hoffbrand AV Binding of serum ferritin to concanavalin A in patients with iron overload and with chronic liver disease . J Clin Pathol 1982 35:481-6.
- Fautrel B, Le Mo?l G, Saint-Marcoux B, Taupin P, Vignes S, Rozenberg S, et al. Diagnostic value of ferritin and glycosylated ferritin in adult onset Still's disease . J Rheumatol 2001 28:322-9.
- Lebrun D, Mestrallet S, Dehoux M, Golmard JL, Granger B, Georgin-Lavialle S, et al. Validation of the Fautrel classification criteria for adult-onset Still's disease . Semin Arthritis Rheum 2018 47:578-585.
- Vignes S, Le Moel G, Fautrel B, Wechsler B, Godeau P, Piette JC Percentage of glycosylated serum ferritin remains low throughout the course of adult onset Still's disease . Ann Rheum Dis 2000 59:347-50.
- Crook MA. Hyperferritinaemia; laboratory implications. Ann Clin Biochem 2012; 49:211-213
The chemical pathology team can be reached via email: chemicalpathologist@adhb.govt.nz or via Lablink (09) 307 4949 ext 22000 or 09-3078995
Emails will receive priority attention from the on-call chemical pathologist. Include the patients NHI.
After-hours: contact Lablink (Auckland City Hospital ext. 22000 or 09-3078995) or hospital operator for on duty staff after hours .
- Dr Samarina Musaad (Clinical Lead) : SamarinaM@adhb.govt.nz ext. 22402
- Dr Cam Kyle : CampbellK@adhb.govt.nz ext 22052
- Dr Weldon Chiu : WeldonC@adhb.govt.nz ext. 23427
- Dr Campbell Heron : CHeron@adhb.govt.nz ext. 23427
- Dr Sakunthala Jayasinghe Saku.Jayasinghe@adhb.govt.nz
- Dr Owen Yi WenyiYi@adhb.govt.nz
- Send samples to Middlemore Hospital (MMH) Lab at 4 o C if receipt time is anticipated to be within 1 week; otherwise freeze specimen at -20 o C and send frozen
- As Glycosylated Ferritin is expressed as percentage of total ferritin, the total ferritin level will be re-measured at MMH laboratory even if it was already done by referring laboratory to avoid any significant inter-platform or inter-instrument variation.