Case report

A 73-year-old normotensive Asian man presented with generalized weakness, dizziness, and palpitations for two weeks. He had experienced such symptoms at frequent intervals since adolescence. In the past, he had also been hospitalized on multiple occasions for fever, chills, rigors, cough, and diarrhea. Seven years ago, he was diagnosed with diabetes mellitus. He did not report anorexia, nausea, vomiting, prolonged bleeding, epistaxis, hematemesis, and melena. He consumed a mixed diet. He had smoked 48 pack-years of cigarettes, and had consumed seven units of alcohol daily for 33 years, from the age of 20 to 53. His family did not have history of similar illnesses or consanguinity.
On examination, the patient appeared ill, and had visible muscle wasting. His vital signs were normal. Pallor was observed; icterus, cyanosis, clubbing, and lymphadenopathy were absent. Respiratory and cardiovascular examination findings were normal. Abdominal examination revealed a distended abdomen with shifting dullness on percussion. The liver was enlarged, and had an irregular surface. The liver span measured 19 cm, and the lower edge was palpated 10 cm below the right subcostal margin. The spleen was enlarged, too, and the splenic notch was palpated 11 cm below the left subcostal margin. The pubic hair had a normal pattern of distribution. Digital rectal examination revealed grade-II prostatomegaly.
The patient was admitted, and investigations were done. Complete blood count revealed the following findings: hemoglobin (Hb), 6.4 g/dL (13.5-17.5); mean corpuscular volume (MCV), 69.4 µm3 (80-100); mean corpuscular Hb (MCH), 20.6 pg/cell (25.4-34.6); mean corpuscular Hb concentration (MCHC), 29.5% (31-36); RBC count, 3.1 million/µL (4.3-5.9); white blood cell (WBC) count, 3870 cells/µL (4000-11000); and platelet count 60000 cells/µL (150000-450000). Liver function test revealed the following findings: total bilirubin, 14 µmol/L (3-21); direct bilirubin, 4 µmol/L (0-5); alanine aminotransferase (ALT), 48 IU/L (5-45); aspartate aminotransferase (AST), 51 IU/L (5-40); alkaline phosphatase (ALP), 48 IU/L (5-45); lactate dehydrogenase (LDH), 422 IU/L (<460); albumin 30 g/L (38-49); prothrombin time (PT), 18 s (11-15); and international normalized ratio (INR), 1.31 (0.8-1.1). Iron profile revealed the following findings: serum ferritin, 1215.9 ng/mL (22-322); serum iron, 188 µg/dL (65-175); transferrin saturation, 94.5% (25-45); and total iron binding capacity, 199 µg/dL (250-450). Other laboratory findings were: fasting blood glucose, 130 mg/dL (70-110); two hours postprandial blood glucose, 190 mg/dL (<140); HbA1C, 5.5 g/dL (4.5-6.4); c-peptide, 3.8 ng/mL (0.78-5.19); and a normal renal function test. Mentzer index, the ratio of MCV (in fL) to RBC count (in millions/µL), was 22.39. Peripheral blood smear showed microcytic RBCs with anisopoikilocytosis, target cells, teardrop cells, few microspherocytes, and schistocytes. High-performance liquid chromatography (HPLC, Bio-Rad D-10 hemoglobin testing system) revealed 5.9% HbA2 (1.5-3.5) and 1.7% HbF (0-2.0). High HbA2, low MCV, and low MCHC indicated BTM. Serological spot tests for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen (HBsAg), and hepatitis C virus (HCV) antibody were negative. The ascitic fluid analysis revealed high serum ascites albumin gradient (SAAG ≥ 1.1 g/dL) and a low total protein (< 2.5 g/dL).
Contrast enhanced computed tomography scan of the abdomen and pelvis revealed HCC in segment IVb of liver along with cirrhosis and portal hypertension (Figure 1). The Child-Pugh score for the severity of liver disease was 10 (Child class C). As the mass was in contact with anterior abdominal wall with loss of fat plane, it was unresectable, and liver transplantation was not possible. The serum alpha-fetoprotein (AFP) was 600 ng/mL (<10).
To rule out hereditary hemochromatosis, the HFE  gene was genotyped by multiplex polymerase chain reaction method, which showed H63D homozygous mutation. Thus, the final diagnosis of BTM with H63D homozygous HH complicated with liver cirrhosis and HCC was made. Body iron stores could not be estimated with magnetic resonance imaging (MRI) due to financial constraints.
Following this, the patient was started on iron chelation therapy with subcutaneous deferoxamine infusion (1 g/day). After one month of treatment, his iron profile was: iron, 170 µg/dL; TIBC, 220 µg/dL; and ferritin, 800 ng/mL. As tumor resection and liver transplantation were not possible, he was discharged on palliative care. His symptoms had improved marginally at the time of discharge. The patient had a son whose genetic analysis could not be performed due to financial constraints, but his iron profile was normal. He was counseled about its necessity to diagnose the disease early.
The patient followed up twice in the next month. His symptoms had not improved further. Unfortunately, he passed away after one month of the last follow-up, at his own home. The immediate cause of death could not be established.