Number | Case number | Age | Sex | Iron Test | End-organ manifestations | Patterns of iron deposition on liver biopsy | Iron overload presented on MRI | Stage* | Known mutation or predicted deleterious variant in HH related gene† | |
Serum ferritin (ng/ml) | Transferrin saturation (%) | |||||||||
1 | H1‡ | 67 | M | 1102 | 92.3 | Liver fibrosis | Predominant in hepatocytes | Liver and Spleen | 3 |
SUGP2 p.R639Q DENND3 p.L708V (homozygote) |
2 | H1-2 (sister) | 77 | F | 365 | 31.1 | Asymptomatic | ND | ND | 2 | SUGP2 p.R639Q |
3 | H13‡ | 26 | M | 7004 | 92.1 | Lethargy, dyspnea, diabetes, cardiopathy | Predominant in hepatocytes | Liver | 3 | HJV p.Q6H/C321X/I281T |
4 | H13-1 (brother) | 27 | M | 6269 | 95.4 | Skin pigmentation, loss of libido, abnormal liver function test | Predominant in hepatocytes | Liver and pancreas | 3 | HJV p.Q6H/C321X/I281T |
5 | H22‡ | 18 | M | 6678 | 100.0 | Abnormal liver function test | Predominant in hepatocytes | ND | 3 |
HJV p.Q6H/C321X/H104R TFR2 p.A75V |
6 | H22-1 (father) | 46 | M | 266 | 56.2 | Asymptomatic | ND | ND | 2 |
HJV p.H104R TFR2 p.A75V |
7 | H25‡ | 33 | M | 421 | 84.0 | Abnormal liver function test | ND | Liver | 3 |
HJV p.E3D TMPRSS6 p.T331M |
8 | H35‡ | 53 | F | 1402 | 49.0 | Lethargy, jaundice, abnormal liver function test | Predominant in hepatocytes | Liver and spleen | 3 |
HJV p.E3D BMP4 p.R269Q |
9 | H35-1 (son) | 30 | M | 79.3 | 46.0 | Asymptomatic | ND | ND | 2 |
HJV p.E3D BMP4 p.R269Q |
10 | H40‡ | 57 | M | 4001 | 93.0 | Abnormal liver function test | Predominant in hepatocytes | Liver | 3 | HJV p.Q6H/C321X/V274M |
11 | H2 | 46 | M | 1100 | 42.5 | Asymptomatic | ND | Liver and Spleen | 2 | DENND3 p.L708V |
12 | H5 | 22 | F | 2995 | 89.1 | Lethargy, skin pigmentation, amenorrhea, abnormal liver function test | Predominant in hepatocytes | Liver and pancreas | 3 | HJV p.Q312X (homozygous) |
13 | H9 | 58 | M | 5949 | 28.4 | Lethargy, diabetes and abnormal liver function test | Predominant in hepatocytes | Liver and spleen | 3 | SLC40A1 p.V162del |
14 | H10 | 62 | F | 5346 | 99.0 | Abnormal liver function test | Predominant in hepatocytes | Liver, spleen and pancreas | 3 | - |
15 | H11 | 48 | F | 7078 | 99.6 | Diabetes, amenorrhea and abnormal liver function test | Predominant in hepatocytes | Liver and spleen | 3 | SLC40A1 IVS3+10delGTT |
16 | H19 | 50 | F | 9272 | 81.6 | Cardiac failure, diabetes, abnormal liver function test | Predominant in hepatocytes | Liver, spleen and pancreas | 3 | - |
17 | H31 | 28 | M | 738 | 46.4 | Jaundice, abnormal liver function test | Predominant in hepatocytes | ND | 3 | DENND3 p.L708V |
18 | H34 | 38 | F | 843 | 96.2 | Skin pigmentation, liver cirrhosis, diabetes, amenorrhea | Predominant in hepatocytes | ND | 3 |
SLC40A1 IVS1-8C/G DENND3 p.L708V |
19 | H41 | 53 | M | 1030 | 96.8 | Cardiac failure, diabetes, liver fibrosis | Predominant in hepatocytes | Liver | 3 | - |
20 | H45 | 46 | M | 2000 | 85 | Abnormal liver function test | ND | Liver, spleen | 3 | - |
21 | H46 | 36 | F | 2000 | 96 | Abnormal liver function test, amenorrhea | Predominant in hepatocytes | Liver | 3 | HJV p.F103L (homozygous) |
22 | H49 | 49 | M | 7445 | 97 | Abnormal liver function test | Predominant in hepatocytes | Liver, spleen | 3 | SLC40A1 p.Y333H |
*According to 2011 hemochromatosis guidelines from the AASLD, stages are defined as follows: Stage one refers to those patients with the genetic disorder with no increase in iron stores; Stage two refers to those patients with the genetic disorder who have phenotypic evidence of iron overload but who are without tissue or organ damage; Stage three refers to those individuals who have the genetic disorder with iron overload and have iron deposition to the degree that tissue and organ damage occurs.
†Whole exome sequencing was conducted for cases with HJV E3D (Cases H1, H25, and H35).
‡Cases with family genetic analysis.
HH, hereditary haemochromatosis; ND, not done.