SNP Shot: Genomic Insights

Dihydropyrimidine dehydrogenase (DPD) deficiency is a condition with varying degrees of severity. Some individuals experience neurological issues, while others show no apparent symptoms.

In severe cases of DPD deficiency, symptoms manifest in infancy. These individuals may exhibit neurological problems such as recurrent seizures (epilepsy), intellectual disability, abnormally small head size (microcephaly), increased muscle stiffness (hypertonia), delayed motor development (e.g., walking), and autistic-like behaviors impacting communication and social skills. Conversely, some individuals with DPD deficiency are asymptomatic, displaying no noticeable signs or symptoms. These individuals may only be identified through laboratory testing.

Individuals with DPD deficiency, regardless of whether they exhibit other symptoms, are at risk of experiencing severe and potentially life-threatening toxic reactions to fluoropyrimidine drugs, commonly used in cancer treatment. Examples include 5-fluorouracil and capecitabine. Because individuals with DPD deficiency cannot effectively break down these drugs, they accumulate to toxic levels in the body, leading to fluoropyrimidine toxicity. This toxicity can cause mucositis (inflammation and ulceration of the gastrointestinal tract lining), resulting in symptoms like mouth sores, abdominal pain, bleeding, nausea, vomiting, and diarrhea. Additionally, fluoropyrimidine toxicity can lead to neutropenia (low white blood cell count), increasing the risk of infections, and thrombocytopenia (low platelet count), impairing blood clotting and potentially causing abnormal bleeding (hemorrhage). Other possible side effects include hand-foot syndrome (redness, swelling, numbness, and peeling of skin on the palms and soles), shortness of breath, and hair loss.

Inheritance:

DPD deficiency follows an autosomal recessive inheritance pattern. This means that an individual must inherit two copies of a mutated *DPYD* gene (one from each parent) to manifest the condition. The severity of these mutations influences whether an individual with two mutated copies will display the characteristic signs and symptoms or remain asymptomatic but vulnerable to fluoropyrimidine toxicity. The parents of an individual with an autosomal recessive condition typically carry one copy of the mutated gene and usually do not exhibit any symptoms themselves. However, even individuals with only one mutated copy of the *DPYD* gene may experience toxic reactions to fluoropyrimidine drugs.