When hepcidin binds ferroportin, ferroportin is phosphorylated, endocytosed, tagged with ubiquitin, and degraded. More than 39 mutations to the SLC40A1 gene have been identified in patients with type 4 hemochromatosis. The misregulation of ferroportin in type 4 hemochromatosis can involve a failure of ferroportin to be properly expressed at the cell membrane, or it can involve a failure of ferroportin to respond to negative regulation by hepcidin.Hemochromatosis type 4A is characterized by impaired iron export in cells. Reticuloendothelial macrophages are most affected. Iron accumulates preferentially in Kupffer cells, which are located in the liver, and serum ferritin increases; less iron is available for circulating transferrin, a protein that binds iron and transports it through the bloodstream to cell receptors. This means that, while iron is trapped in certain types of tissues, it cannot be transported to tissues where it is needed. The accumulation of iron in tissues due to impaired iron export can lead to increasing transferrin iron saturation and liver parenchymal iron overload in advanced stages of the disease. More ferritin is produced to suppress oxidative cell damage, although the amount of ferritin that cells can accumulate is limited.Hemochromatosis type 4B is characterized by abnormal iron release from macrophages and enterocytes because the mutant ferroportin is resistant to the hepcidin protein, which serves a regulatory function in wild-type ferroportin. Intestinal iron absorption and release of iron from macrophages is increased. Thus, this form of the disease leads to elevated transferrin saturation levels. Systemic iron overload results, and liver iron deposition is primarily in the hepatocytes.
Associated conditions
Patients with a horseshoe kidney can develop sequelae related to the abnormal anatomy and present with symptoms related to them.The general categories a horseshoe kidney may increase the risk for fall under the following categories:

Kidney obstruction – commonly causes ureteropelvic junction obstruction (UPJ) which is a blockage at the area where the ureter connects to the renal pelvis. This can lead to urinary stasis which can promote infection and stone formation. Kidney infections – associated with vesicoureteral reflux (present in approximately 50% of all patients with renal fusion) which is an abnormal reflux of urine back into the ureters that increases risk of urinary tract infections. Kidney stones – deviant orientation of kidneys combined with slow urine flow and kidney obstruction may increase the risk of developing kidney stones. Treatment is further complicated if patient possesses aberrant skeletal anatomy. It is estimated 36% of patients with horseshoe kidneys will develop kidney stones. Kidney cancer – increased frequency of certain renal cancers such as transitional cell tumors, Wilms tumors, and carcinoid tumors. Heart abnormalities – ventricular septal defect
Neurological abnormalities - encephalocoele, myelomeningocoele, spina bifida
Skeletal abnormalities - kyphosis, scoliosis, hemeivertebra, and micrognathia. Genitourinary abnormalities - septate vagina, bicornuate uterus, hypospadias, undescended testis, adult polycystic kidney disease, and more than two kidneys. Genetic abnormalities - Turner syndrome, Down syndrome, Patau syndrome, Edward syndrome, oro-cranial-digital syndrome

Cause
There have been several proposed factors that may contribute to the development of a horseshoe kidney. Different exposures to the developing fetus such as different teratogens (e.g.