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CASE REPORT |
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Year : 2015 | Volume
: 8
| Issue : 1 | Page : 95-97 |
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Anemia with jaundice: An unusual cause
K. V. S. Hari Kumar, AK Gupta
Department of Medicine, Command Hospital, Chandimandir, Haryana, India
Date of Web Publication | 8-Jan-2015 |
Correspondence Address: K. V. S. Hari Kumar Department of Medicine, Command Hospital, Chandimandir - 134 107, Haryana India
Source of Support: None, Conflict of Interest: None | Check |
DOI: 10.4103/0975-2870.148865
Anemia and jaundice are two important clinical signs in medicine. Occurrence of these two signs together in a patient suggests hemolytic disorders. Hemochromatosis is a disease characterized by hyperpigmentation, arthralgia and diabetes. The disease usually presents in elderly individuals and is rare in menstruating females. We present a case of a young lady with anemia and unexplained jaundice with extensive work-up leading to the diagnosis of hereditary hemochromatosis with megaloblastic anemia. We present the case to highlight the unusual presentation of anemia and jaundice in a case of hemochromatosis. Keywords: Hemochromatosis, hepatocellular jaundice, megaloblastic anemia
How to cite this article: Kumar KH, Gupta A K. Anemia with jaundice: An unusual cause. Med J DY Patil Univ 2015;8:95-7 |
Introduction | | |
Hereditary hemochromatosis is an inherited disorder characterized by excess iron deposition in tissues. The disease is silent in heterozygous form and presents with iron overload state in homozygous individuals. HFE gene mutations located on chromosome 6p, are responsible for the majority of the disease. [1] The disease presents with hepatomegaly, increased skin pigmentation, arthralgia and endocrine features such as diabetes and hypogonadism. The disease is rarely seen in premenopausal females due to the natural protection of menstrual blood loss. The patients with hemochromatosis are usually managed with phlebotomy coupled with iron chelating agents. [2]
Hematological picture is unremarkable in most cases of hemochromatosis and anemia is uncommon due to the availability of excess iron for hematopoiesis. Anemia is reported in hereditary hemochromatosis associated with hemolytic anemia's and congenital dyserythropoietic anemia. [3] The presence of anemia with jaundice suggests an underlying hemolytic disorder with unconjugated hyperbilirubinemia. However, conjugated hyperbilirubinemia with anemia poses a diagnostic dilemma. We recently encountered a young lady who presented with prolonged unexplained jaundice with anemia. Extensive work-up leads us to the diagnosis of hereditary hemochromatosis and megaloblastic anemia and we present the same in this report.
Case Report | | |
A 41-year-old female patient presented with a history of yellowish discoloration of the eyes and urine of 2 weeks duration. The patient denied history of bleeding tendencies, swelling legs, distension of abdomen, hematemesis, melena and pruritus. She denied a history of blood transfusions, intravenous drug abuse or alcohol consumption. She had no musculoskeletal complaints and her menses were regular. She had normal appetite and sleep rhythm with no symptoms of encephalopathy. She denied previous therapy with iron supplements, chronic blood loss and past history of blood transfusions. She denied a past history of diabetes, hypertension or tuberculosis and similar history in the family. Examination revealed normotensive lady with pallor, pedal edema and icterus. There was no evidence of chronic liver disease such as spider nevi and palmar erythema. Abdominal examination revealed hepatosplenomegaly without ascites. Other systemic examination was essentially normal.
Her investigations revealed anemia (Hemoglobin-7.1 g/dL, Mean Corpuscular Volume-116 fl) with no evidence of hemolysis. Peripheral blood smear showed macrocytosis with hypersegmented neutrophils. Her serum bilirubin was 12.3 mg/dL, (conjugated-10.1), alanine aminotransferase -340 U/L, aspartate aminotransferase-425 U/L, alkaline phosphatase-98 U/L, serum proteins 64 g/L, albumin 38 g/L, globulin 26 g/L and international normalized ratio was 2.36. Other biochemical parameters including glucose and lactate dehydrogenase were normal. Serum vitamin B12 (92 pg/mL) and folic acid (2 μg/L) were decreased. Ultrasonography revealed slightly enlarged liver and spleen with no focal deficit. She was considered as a case of viral hepatitis with macrocytic anemia and was treated with hematinics and B12/folate replacement.
The patient's hemoglobin improved rapidly and the viral marker screen was negative for all hepatotropic viruses. The patient was investigated for other atypical causes of hepatitis and was noticed to have a diffuse increase in skin pigmentation [Figure 1]. Immunological profile of autoimmune hepatitis was negative including antinuclear antibodies, anti-liver-kidney-mitochondrial antibodies. Magnetic resonance imaging of the abdomen showed a diffusely increased echogenicity of the liver and spleen in comparison with other tissues [Figure 2]. Her total iron binding capacity-224 μg/dL (normal 230-400), serum iron 190 μg/dL (normal 80-176), ferritin-1210 ng/mL (normal 30-280) and transferrin saturation (85%) were suggestive of iron excess state. Upper Gastrointestinal endoscopy revealed no varices and normal gastric mucosa. Bone marrow examination for megaloblasts was not carried out due to the coagulopathy and established diagnosis. She was diagnosed as a case of hemochromatosis with early hepatic dysfunction in association with megaloblastic anemia due to B12 and folate deficiency. All the screened family members had normal iron parameters and we could not perform the genetic analysis for hemochromatosis due to lack of facilities at our center. The financial condition of the patient precluded the genetic analysis at another center. She was treated with oral deferiprone and the hematinics. During the last follow-up after 6 months of therapy, her hemoglobin improved to 12 g/dL with complete normalization of hepatic dysfunction. The liver function tests including coagulation parameters were normal during last follow-up and her total iron binding capacity-295 μg/dL, serum iron 127 μg/dL, ferritin-322 ng/mL showed a trend toward improvement. | Figure 1: Recent (a) and old (b) photograph of the patient along with daughter's hand (c) for comparison, highlighting the change in skin color
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| Figure 2: Magnetic resonance imaging abdomen showing increased signal intensity of liver and spleen
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Discussion | | |
Our case is unique in its presentation with prolonged unexplained jaundice. Initial presentation was similar to viral hepatitis, but the detailed work-up lead to the diagnosis of hemochromatosis with megaloblastic anemia. Hemochromatosis is a disorder characterized by increased absorption and storage of iron. The disease may remain silent even in advanced stages and the common presentations include musculoskeletal or hepatic features. Presence of co-existing diseases like pernicious anemia may have a protective role and prevent the full manifestation of the disease. [4] Diabetes and hypogonadism are common due to iron deposition but are absent in our patient. The typical symptoms of hemochromatosis include polyarthralgia seen in about 60-70% of the patients. The absence of arthralgia and diabetes in our patient could be explained by her premenstrual status, megaloblastic anemia and early identification of the disease without significant tissue iron deposition. Previous reports also suggest that hereditary hemochromatosis may remain undiagnosed for >10 years even with typical symptoms. [5] The HFE mutation has poor penetrance with <1% of homozygous individuals manifesting the disease. [6] The presence of co-existing megaloblastic anemia also masks the clinical features and delayed the development of cirrhosis in our patient. Genetic analysis for the HFE mutation conclusively establishes the diagnosis but could not be performed due to lack of facilities.
Hereditary hemochromatosis is a condition with iron excess and the patients usually have normal hemoglobin concentration. The presence of anemia in a patient with hemochromatosis could be explained by the association of hemolytic anemia's with hemochromatosis. [3] Previous reports describe the association of sickle cell disease, thalassemia, dyserythropoietic anemia and hereditary spherocytosis with hemochromatosis. [7] There is also an interesting link between HFE gene and anemia of chronic disease (ACD). In conditions of iron excess, the HFE gene signals to hepcidin, which decreases the body iron stores. [8] Thus, HFE gene has an important role in the pathogenesis of ACD.
In our case, the diagnosis of hemochromatosis was missed initially, due to the absence of musculoskeletal complaints and diabetes. However, prolonged jaundice with no apparent underlying etiology lead us to explore the case further. Her change of appearance was so gradual that patient did not complain about the darkening of the skin. The presence of anemia also misled us not to consider a diagnosis of hemochromatosis. The treatment of hereditary hemochromatosis includes dietary modifications, phlebotomy for non-anemic patients and iron chelating agents. The clinical stage of the disease determines the therapeutic options and the associated response. The disease is managed by phlebotomy alone in the initial stages and iron chelators in advanced disease. The presence of megaloblastic anemia precluded us to use the option of phlebotomy and hence we resorted to the use of iron chelating agents.
Conclusion | | |
We present an interesting case of prolonged jaundice with anemia due to hereditary hemochromatosis and macrocytic anemia. Our case highlights the need of looking for alternate etiology in atypical cases of jaundice and anemia.
References | | |
1. | Crownover BK, Covey CJ. Hereditary hemochromatosis. Am Fam Physician 2013;87:183-90. |
2. | Panigrahi I, Ahmad F, Kapoor R, Sharma PK, Makharia G, Saxena R. Evidence for non-HFE linked hemochromatosis in Asian Indians. Indian J Med Sci 2006;60:491-5. [ PUBMED] |
3. | Fargion S, Valenti L, Fracanzani AL, Sampietro M, Cappellini MD, Scaccabarozzi A, et al. Hereditary hemochromatosis in a patient with congenital dyserythropoietic anemia. Blood 2000;96:3653-5. |
4. | Bonafoux B, Henry L, Delfour C, Arnaud A, Brun S, Mercier E, et al. Association of familial pernicious anaemia and hereditary haemochromatosis. Acta Haematol 2008;119:12-4. |
5. | Bulaj ZJ, Ajioka RS, Phillips JD, LaSalle BA, Jorde LB, Griffen LM, et al. Disease-related conditions in relatives of patients with hemochromatosis. N Engl J Med 2000;343:1529-35. |
6. | Beutler E, Felitti VJ, Koziol JA, Ho NJ, Gelbart T. Penetrance of 845G - > A (C282Y) HFE hereditary haemochromatosis mutation in the USA. Lancet 2002;359:211-8. |
7. | Conrad ME. Sickle cell disease and hemochromatosis. Am J Hematol 1991;38:150-2. |
8. | Singh B, Arora S, Agrawal P, Gupta SK. Hepcidin: A novel peptide hormone regulating iron metabolism. Clin Chim Acta 2011;412:823-30. |
[Figure 1], [Figure 2]
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