Genetic diagnosis history and osteoarticular phenotype of a non-transfusion secondary hemochromatosis

BACKGROUND It is not easy to identify the cause of various iron overload diseases because the phenotypes overlap. Therefore, it is important to perform genetic testing to determine the genetic background of patients. AIM To investigate the genetic background of a patient with hemochromatosis complicated by psoriasis on both lower extremities. METHODS Ten years ago, a 61-year-old male presented with iron overload, jaundice, hemolytic anemia and microcytic hypochromic anemia. Computed tomography of the left knee joint showed enlargement of the tibial medullary cavity and thinned bone cortices. Magnetic resonance imaging showed hepatic hemochromatosis, extensive abnormal signals from bone marrow cavities and nodular lesions in the lateral medullary cavity of the upper left lateral tibia. Single photon emission computed tomography showed radial dots of abnormal concentration in the upper end of the left tibia and radial symmetry of abnormal concentrations in joints of the extremities. The patient showed several hot spot mutations of the HFE and G6PD genes detected by next-generation sequencing, but no responsible gene mutation was found. The thalassemia gene was detected by gap-PCR. RESULTS The patient was found to carry the -α4.2 and --SEA deletion mutations of the globin gene. These two mutations are common causes of Southeast Asian α-thalassemia, but rarely cause severe widespread non-transfusion secondary hemochromatosis osteoarthropathy. The simultaneous presence of an auxiliary superposition effect of a rare missense mutation of the PIEZO1 gene (NM_001142864, c.C4748T, p.A1583V) was considered. Moreover, several rare mutations of the IFIH1, KRT8, POFUT1, FLG, KRT2, and TGM5 genes may be involved in the pathogenesis of psoriasis. CONCLUSION The selection of genetic detection methods for hemochromatosis still needs to be based on an in-depth study of the clinical manifestations of the disease.