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When Hypotransferrinemia Obscures the Diagnosis of Hereditary Hemochromatosis: a Case Report

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When Hypotransferrinemia Obscures the Diagnosis of Hereditary Hemochromatosis: a Case Report Chris Whittington, MB BS, MBA, FCFP, FACRRM When hypotransferrinemia obscures the diagnosis of hereditary hemochromatosis: A case report A patient with an iron overload disorder benefits from genetic test- ing that has become more readily available in BC. ABSTRACT: By impairing erythro- Case data blood pressure was normal. An ultra- poiesis, hypotransferrinemia may A thin 53-year-old white male who sound image of his liver showed a cause anemia. Hypotransferrinemia had been diagnosed with hypotransfer- slightly enlarged organ but no other may also be a rare cause of iron over- rinemia 5 years previously presented abnormalities. A different laboratory load. Another common cause of iron for reinvestigation of iron overload. with differing standards was used in overload is C282Y homozygous At the time that the patient’s hypo- the follow-up evaluation. The patient’s hemochromatosis. While it is unusu- transferrinemia was initially docu- ferritin level was 623 μg/L and his al to find the two disorders in the mented, he had a ferritin level of liver function tests were normal. He same patient, in this case, a 53- 465 μg/L (normal 15–250 μg/L). His had a slightly elevated cholesterol year-old male was found to have both transferrin level was 1.91 g/L (normal level at 5.6 mmol/L (normal 2.0–5.2 conditions. 2.20–3.80 g/L), and total iron-binding mmol/L). His renal function, thyroid capacity (TIBC) was reduced at 39 function, fasting blood sugar level, μmol/L (normal 45–73 μmol/L), in complete blood count, serum cerulo- concert with the hypotransferrinemia. plasmin, and copper levels were all He had borderline anemia and his normal. Total iron was elevated at 32 major complaint was fatigue. μmol/L (normal 9–30 μmol/L) and It was felt at the time of his initial TIBC was reduced at 41 (normal diagnosis that the patient might have 45–70 μmol/L). The TS was 78% an undiagnosed “chronic disease” as (normal 15%–55%). The elevation of well, but hemochromatosis was not the TS was partly explained by the low considered because his transferrin sat- TIBC, as the TS was calculated using uration (TS) was too low at 79%. He the total iron and TIBC. was advised to donate blood and to Consideration was then given to decrease vitamin C and iron intake. the possibility of the patient having With advances in the understand- type 4 hemochromatosis or ferro- ing of iron overload it was decided to portin disease because of the previous reinvestigate the patient 5 years after borderline anemia, high ferritin value, the initial diagnosis of hypotransfer- possible spuriously elevated TS, and rinemia. At this time he was still com- plaining of unremitting fatigue. On Dr Whittington is a clinical associate pro- examination the patient displayed a fessor of family practice at the University of grayish-yellow discoloration of the British Columbia and a staff member at skin. There was no palpable liver or MSA General Hospital, Abbotsford, British stigmata of chronic liver disease. His Columbia. 24 BC MEDICAL JOURNAL VOL. 49 NO. 1, JANUARY/FEBRUARY 2007 When hypotransferrinemia obscures the diagnosis of hereditary hemochromatosis: A case report no evidence of dysmetabolic hepatosi- derosis. Ferroportin disease presents with a variable clinical phenotype. Transferrin saturation may be normal or elevated, ferritin level is elevated, Hypotransferrinemia is a rare disorder, and venesection therapy is often complicated by the development of but it may be more common than is anemia.1 Type 1 or HFE hemochro- clinically diagnosed and may complicate matosis is the most common form of hemochromatosis.2 Because of the the diagnosis of patients with anemia increased availability of HFE gene and other coexisting disorders. testing for first-line genetic investiga- tion of iron overload, the decision was made to test for this disorder before any testing for ferroportin disease was initiated. HFE gene testing subsequently revealed the patient to be a C282Y homozygote. He then underwent vene- predisposition and the recurrent bor- References section for the removal of 12 units of derline anemia produced by venesec- 1. Pietrangelo A. The ferroportin disease. blood (equivalent to 3 g of iron) over 14 tion therapy. Paradoxically, in C282Y Blood Cells Mol Dis 2004;32:131-138. months until his ferritin level reached homozygous hemochromatosis body 2. Feder JN, Gnirke A, Thomas W, et al. A 66 μg/L. The iron reduction was delib- hair loss correlates with markedly novel MHC class I-like gene is mutated in erately prolonged as venesection ther- increased iron stores and is related to patients with hereditary haemochro- apy tended to precipitate red blood hypogonadism. matosis. Nat Genet 1996;13:399-408. cell, hemoglobin, and hematocrit val- 3. Knisely AS, Gelbart T, Beutler E. Molecu- ues below the normal range. After iron Summary lar characterization of a third case of reduction, the patient’s fatigue did not Hypotransferrinemia is a rare disor- human atransferrinemia. Blood 2004; improve and he complained of balding. der, but it may be more common than 104:2607. However, his complexion assumed a is clinically diagnosed and may com- 4. Beutler E, Gelbart T, Lee P, et al. Molecu- more normal hue and a follow-up ultra- plicate the diagnosis of patients with lar characterization of a case of atransfer- sound image of the liver was normal. anemia and other coexisting disor- rinemia. Blood 2000;96:4071-4074. ders. This can be seen in the case re- 5. Stavem P, Saltvedt E, Elgjo K, et al. Con- Discussion ported here, where a 53-year-old male genital hypochromic microcytic anaemia Hypotransferrinemia is a relatively who had been diagnosed with hypo- with iron overload of the liver and hyper- rare condition and is held to be auto- transferrinemia 5 years earlier pre- ferraemia. Scand J Haematol 1973;10: somal recessive.3-5 In hypotransfer- sented with iron overload. The avail- 153-160. rinemia the transferrin deficiency ability of HFE gene testing made it 6. Ponka P. Rare causes of hereditary iron causes dietary nontransferrin-bound possible to consider coexisting hered- overload. Semin Hematol 2002;39:249- iron to be deposited in the liver via itary hemochromatosis. The patient 262. the portal circulation.6 Impaired eryth- tested positive for two copies of the ropoiesis can also occur due to the C282Y mutation and was then treated decreased availability of transferrin for coexisting hypotransferrinemia to transport iron to erythrocytes, and and C282Y homozygous hemochro- anemia may result. matosis. It is possible that in this case the concomitant C282Y homozygosity Competing interests mitigated the tendency to anemia in None declared. the patient. The patient’s balding was likely due to a combination of genetic VOL. 49 NO. 1, JANUARY/FEBRUARY 2007 BC MEDICAL JOURNAL 25.
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