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Definition Hereditary hemochromatosis is an inherited disorder that leads to iron overload due to excessive absorption of dietary iron because of a deficiency of hepcidin, which is an iron regulatory peptide hormone. A homozygous C282Y mutation in HFE is responsible for the vast majority of hereditary cases. However, iron overload due to hyperabsorption of dietary iron may result from other genetic mutations, chronic anemias associated with…
Definition Wilson disease is an autosomal recessive disorder of copper transport. Affected individuals accumulate toxic levels of copper in the liver and later in the brain as a consequence of mutations in both alleles of the Wilson disease gene ( ATP7B ). The gene encodes a copper-transporting ATPase expressed primarily in hepatocytes in the liver, where its major function is excretion of hepatic copper into the…
Definition The porphyrias, which are a group of disorders that arise from disturbances in heme synthesis, are characterized by the accumulation of porphyrins or their precursors on the heme biosynthetic pathway. Most porphyrias are genetic and heritable, except for the sporadic form of porphyria cutanea tarda and rare instances of porphyria arising from acquired somatic mutations. Approximately 90% of heme biosynthesis occurs within the erythron, where…
Definition Homocysteine, which is a nonprotein amino acid, is a key metabolic branch point metabolite between the trans-sulfuration and remethylation pathways of methionine metabolism. The many conditions associated with high homocysteine levels encompass a wide range of clinical manifestations. The normal level of plasma total homocysteine is below 15 µM. However, the threshold of total homocysteine above which a disorder of homocysteine metabolism should be suspected…
The lysosomal storage diseases encompass a group of more than 70 different inherited disorders, all sharing a defect in lysosomal function. Lysosomes are acidic, membrane-bound organelles that are located in the cytoplasm and contain enzymes that degrade macromolecules. Lysosomal storage disorders ensue when one or more of the hydrolytic enzymes are deficient or when essential lysosomal transporters, receptors, cofactors, or protective proteins are defective or lacking.…
Definition Glycogen storage diseases are a group of disorders resulting from inherited defects in the biochemical pathways of glycogen metabolism. Based on organ involvement, glycogen storage diseases are broadly categorized into two groups: hepatic glycogen storage diseases and muscle glycogen storage diseases. Epidemiology The individual incidence rate of each glycogen storage disease is very rare. However, the collective incidence of all glycogen storage diseases is approximately…
Disorders of lipid metabolism are an increasingly common consequence of modern industrial lifestyles. With increasing prosperity, the spread of Western-style diets and sedentary habits is resulting in dramatic rises in obesity in countries around the world. Poor lifestyle habits coupled with genetic predisposition commonly result in dyslipidemia, which is characterized by higher levels of the atherogenic cholesterol- and triglyceride-rich apolipoprotein (apo) B-100 lipoproteins, higher levels of…
Overview Definition The definition of inborn errors of metabolism includes not only enzyme deficiencies but also any condition in which perturbation of a biochemical pathway is intrinsic to the pathobiology of the disorder. Inborn errors of metabolism can be classified as disorders that result in the accumulation or deficiency of small molecules, thereby leading to intoxication disorders; the abnormal accumulation or deficiency of complex molecules such…
Melanoma Epidemiology The incidence of melanoma continues to rise rapidly worldwide, but mortality rates are declining. Each year in the United States, nearly 100,000 new cases of invasive melanoma are detected, and approximately 7000 patients die from melanoma. Melanoma is the leading cause of death from cutaneous malignant disease, and it accounts for 1 to 2% of all cancer deaths in the United States. The rising…
Bone Tumors Primary bone tumors include osteosarcomas, chondrosarcomas, and Ewing sarcoma. These rare tumors, which arise from the normal cellular components of bone and can potentially metastasize, have an incidence of 1.8 new cases per 100,000 population per year and account for only 0.2% of all cancers. Tumors that originate in other organs can metastasize to bone and represent the vast majority of bone cancers in…
Epidemiology Prostate cancer is the most common nonskin cancer that affects U.S. men, with approximately 270,000 new cases diagnosed annually and approximately 35,000 deaths each year. Worldwide, approximately 1.4 million cases of prostate cancer are diagnosed annually and lead to approximately 375,000 deaths each year. The disease is the most common cancer among men in much of Europe, North America, and Australia, but lower rates are…
Epidemiology Testicular cancer has an annual incidence of about 8700 cases per year in the United States and accounts for only 1% of all male malignancies. Nevertheless, it is the most common carcinoma in men ages 15 to 35 years. In the United States, testicular cancer is four to five times more common in White men compared with men of other ethnicities, but incidence rates are…
Gynecologic cancers are not common, but earlier diagnosis is always associated with improved survival and a greater chance for cure. Although most care is provided by gynecologic surgeons and oncologists, patients may first present to other physicians with signs or symptoms that require evaluation. Furthermore, all physicians share responsibility for encouraging recommended cancer screening. Cervical Cancer Epidemiology Cancer of the uterine cervix is the third most…
Breast Cancer Epidemiology and Pathobiology Invasive breast cancer, which is the most common nonskin cancer in women in the United States, is diagnosed in approximately 290,000 women annually and results in approximately 43,000 deaths each year. Worldwide, about 2.25 million cases are diagnosed annually. The incidence and mortality from breast cancer appear to be declining in the United States and parts of Western Europe, likely because…
Renal Cell Carcinoma Definition Cancers of the kidney are a heterogeneous group of neoplasms, the majority of which are of epithelial origin and malignant. Renal cell carcinoma, classically referred to as clear cell carcinoma or hypernephroma, is not a single malignancy. Rather, renal cell carcinoma comprises a group of distinguishable entities ( Table 182-1 ), each with a strong relationship between its morphologic and genetic features.…
Definition Cancers arising from the liver and biliary tract include hepatocellular carcinoma, cholangiocarcinoma, and gallbladder adenocarcinoma, as well as other less common malignant histologies ( E-Table 181-1 , Fig. 181-1 ). Cholangiocarcinomas are further subclassified by their anatomic location along the biliary tract: intrahepatic (also known as peripheral) or extrahepatic, which includes hilar (also known as Klatskin tumors) and distal locations. These cancers collectively represent the…
Definition More than 90% of pancreatic tumors are adenocarcinomas that arise from the ductal epithelium. Other major tumors of the pancreas include acinar cell, intraductal papillary mucinous neoplasm, mucinous cystic neoplasm, mixed histology, endocrine malignancies, carcinoid tumors, lymphomas, and a variety of rare sarcomas. Epidemiology Pancreatic ductal adenocarcinoma has one of the highest mortality-to-incidence ratios of any disease. Although it represents the tenth leading cause of…
Neoplasms of the Small Intestine Epidemiology Small bowel malignancies are relatively rare and account for only approximately 3% of all cancers involving the gastrointestinal (GI) tract and less than 0.5% of all cancers in the United States. In 2022, an estimated 11,790 new cases of small bowel cancers will be diagnosed, and this disease accounts for nearly 1960 deaths annually. The four major histologic subtypes, which…