In many patients, mitochondrial disease is caused by an inherited gene mutation or multiple mutations.
In others, external environmental factors may be responsible for mitochondrial dysfunction.
Many different types of mito can develop in patients in contrasting ways. It often takes more work for healthcare teams to de!ne direct causes. Primary mitochondrial disease (PMD) exists from birth, and is genetic, meaning that the disease is inherited or passed down from one or both parents. In some rare cases, mito can be caused by a “spontaneous mutation”, meaning it occurs randomly at or before conception.
Within the mitochondria are two types of genetic material, mitochondrial DNA (mtDNA) and nuclear DNA (nDNA). mtDNA is passed on from the mother to her children, and nDNA is passed on from both parents.
Maternal inheritance is defined as a mother with a mitochondrial DNA (mtDNA) gene mutation that passes along the mutation to all of her children. Typically, all children will be affected but with varying degrees of severity, from no symptoms to severe disease. This does not mean that all of her children will be affected in the same way, and it is rarely possible to predict how children will be affected. This may cause stress for family planning.
Mitochondrial diseases and disorders can be caused in a variety of different ways, and knowing how a person with mito got their disorder/disease may help with understanding family history or family planning.
Autosomal recessive inheritance is when the nuclear DNA (nDNA) that makes up part of the mitochondria is inherited by both parents, half from each. Autosomal recessive mitochondrial disease can only be passed on if BOTH parents are carriers. Meaning, each parent carries the mutated gene but not the disease, so they do not have any symptoms. When both parents are carriers, there is a 25% chance of having a child that will not carry the mutation nor the disease, a 25% chance of having a child with mito and a 50% chance of having a child who will carry the mutation but will not have mito.
Autosomal dominant inheritance occurs if one parent has a dominant nDNA gene mutation and the other parent does not have any nDNA mutations, 50% of their children will inherit the mutation with the disease and symptoms, and 50% of their children will inherit normal genes; therefore, no disease or symptoms.
X-linked inheritance conditions are caused by genetic variants on the X chromosome, one of the two sex chromosomes. Because females have two X chromosomes and males only one, the disorders can appear different in the two sexes. Males are nearly always more severely affected than females. The rules for inheritance are also different since men cannot transmit X-linked genes to their sons but will always transmit them to their daughters.