Succinate dehydrogenase (SDH) is an enzyme complex found within the mitochondria of cells, which are often called the “powerhouses” of the cell. Being an SDH carrier means an individual has inherited a mutation in one copy of an SDH gene. While one copy carries this change, the other remains normal and functional. This genetic status does not mean a person has a disease, but rather that they carry a predisposition.
What Being an SDH Carrier Means
SDH plays a dual role in cellular energy production, participating in both the Krebs cycle and the electron transport chain. Specifically, it converts succinate to fumarate and transfers electrons for ATP generation. A mutation in one of the SDH genes, commonly SDHA, SDHB, SDHC, SDHD, or SDHAF2, can lead to reduced SDH enzyme activity. This causes succinate to accumulate in the cell. This accumulation can interfere with normal cellular processes and increase the risk of developing certain health conditions, although it does not guarantee their occurrence.
Health Conditions Linked to SDH Carriers
SDH carriers have an increased risk of developing specific types of tumors. These include hereditary paraganglioma-pheochromocytoma syndrome (HPPS), which involves tumors arising from neuroendocrine tissues, often in the head, neck, abdomen, or adrenal glands. Gastrointestinal stromal tumors (GISTs), a type of tumor found in the digestive tract, are also linked to SDH mutations, particularly those that often occur in the stomach. Certain kidney cancers, known as renal cell carcinomas, are observed in SDH carriers. Regular monitoring and early detection efforts are important for carriers to manage these potential health implications.
Inheritance and Family Impact
SDH mutations are inherited in an autosomal dominant pattern, meaning each child of an SDH carrier has a 50% chance of inheriting the mutation. For SDHD and SDHAF2 genes, a paternal inheritance effect means the risk of developing a tumor is higher if the mutation is inherited from the father. This inheritance pattern has broader implications for family members, including parents, siblings, and children, as they may also be carriers. Genetic counseling is recommended for SDH carriers and their relatives to understand these risks, explore genetic testing options, and make informed decisions about family health management and planning.