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.