An individual with an organic acidemia has a change in their DNA that causes certain proteins to not work properly. These proteins are responsible for breaking down certain nutrients, often amino acids. Organic acidemias are recessive conditions because they require both copies of the gene to be altered. An individual with only one altered allele is called a carrier. Often, the type of change in DNA can play a role in how severe the disease presents. However, even two individuals with the same clinically diagnosed organic acidemia and genetic variant can have a greatly different expression of the condition, due to other environmental or biological factors. This means that even people with the same genetic diagnosis may not experience the condition the same way and therefore require separate and individualized treatment. 

Genotype and phenotype information work together in informing precision medicine. The genotype identifies the specific disease-causing variant, while the phenotype is the clinical presentation. For organic acidemias, phenotypes can include symptoms like poor feeding, vomiting, lethargy, and metabolic decompensation, as well as biochemical features like organic acid buildup. Studying both is important because the features of a rare disease alone are not specific enough to distinguish it from conditions caused by different variants.

By documenting physical features and symptoms along with genetic findings, researchers can correlate phenotypic data with genetic variants to better define the full spectrum of a genetic disorder and ultimately guide more targeted treatment. In organic acidemias, certain variants may have a greater risk of specific health complications. For example, propionic acidemia (PA) in an infant can include neurological disorders presenting as lethargy or seizures. Later onset of PA can be triggered through a metabolic crisis resulting in developmental delays, movement disorders, or, most commonly, cardiac abnormalities. Glutaric Acidemia Type 1 (GA-1) in an infant is most commonly characterized by an unusually large head and, if left untreated, can lead to a metabolic crisis, most commonly resulting in involuntary movement disorders.

It is important to let researchers know what genetic variants are causing diseases. Patients can contribute data to longitudinal and natural history studies to help researchers better understand rare diseases, ultimately leading to more individualized and impactful treatment options for those living with organic acidemias. OAA now collects genetic information in our Organic Acidemia Natural History Registry. If you would like to contribute to this type of research, simply upload a PDF copy of your genetic report to the registry. If you don’t feel comfortable sharing your report, it is not required. You can participate in other registry-sponsored research without completing the genetic survey. If you participate in the genetic survey but don’t want to participate in the future, you can request that your data be removed from the registry.