Additional symptoms of NPC include facial pain or numbness, blurred or double vision, trouble opening the mouth, or recurring ear infections. If the ear infection does not present with an upper respiratory tract infection, then an examination should be done on the nasopharynx. This is due to the fact that, in adults, ear infections are less common than in children. Signs and symptoms related to the primary tumor include trismus, pain, otitis media, nasal regurgitation due to paresis (loss of or impaired movement) of the soft palate, hearing loss and cranial nerve palsy (paralysis). Larger growths may produce nasal obstruction or bleeding and a "nasal twang". Metastatic spread may result in bone pain or organ dysfunction. Rarely, a paraneoplastic syndrome of osteoarthropathy (diseases of joints and bones) may occur with widespread disease. Causes
NPC is caused by a combination of factors: viral, environmental influences, and heredity. The viral influence is associated with infection with Epstein–Barr virus (EBV). The Epstein-Barr virus is one of the most common viruses. 95% of all people in the U.S. are exposed to this virus by the time they are 30–40 years old. The World Health Organization does not have set preventative measures for this virus because it is so easily spread and is worldwide. Very rarely does Epstein-Barr virus lead to cancer, which suggests a variety of influencing factors. Other likely causes include genetic susceptibility, consumption of food (in particular salted fish) containing carcinogenic volatile nitrosamines.
Because iron export is impaired, iron is unavailable for transport by circulating transferrin. This iron unavailability potentially leads to mild anemia in type 4A hemochromatosis patients because iron is necessary for hemoglobin synthesis, and red blood cells have a relatively high turnover rate. Over time, iron stores increase, and individuals with type 4A hemochromatosis may develop hepatic fibrosis.The symptoms of type 4B hemochromatosis tend to be more severe. They resemble the symptoms of hemochromatosis types 1, 2, and 3. Plasma iron concentration is elevated, and symptoms include joint pain, diabetes, and arrhythmia. Liver iron deposition tends to be greater in type 4B than in type 4A. Liver damage occurs more frequently in this form of hemochromatosis than in type 4A, and some individuals develop cirrhosis of the liver. Genetics
Type 4 hemochromatosis is caused by mutations of the SLC40A1 gene, located on the long arm of chromosome 2, specifically at 2q32.2. The SLC40A1 gene encodes ferroportin, a protein responsible for exporting iron from cells in the intestine, liver, spleen, and kidney, as well as from reticuloendothelial macrophages and the placenta. More than 39 mutations to the SLC40A1 gene have been identified in patients with type 4 hemochromatosis. All reported SLC40A1 mutations are deletions or missense mutations, which lead to amino acid substitution.Mutations to SLC40A1 that change the amino acid sequence can result in loss of function or gain of function for the resulting ferroportin protein.