SNP Shot: Genomic Insights

Dihydropyrimidinase deficiency is a condition that can manifest with neurological and gastrointestinal issues in some patients. However, others with this deficiency may show no noticeable symptoms, and their diagnosis relies solely on laboratory findings.

Common neurological symptoms associated with dihydropyrimidinase deficiency include intellectual disability, seizures, and reduced muscle tone (hypotonia). Some individuals also experience an unusually small head (microcephaly) and autistic-like behaviors that impact their communication and social skills.

Gastrointestinal complications of dihydropyrimidinase deficiency can include gastroesophageal reflux (where stomach acid flows back into the esophagus) and recurring episodes of vomiting (cyclic vomiting). Affected individuals may also develop villous atrophy, a condition where the villi (small projections in the small intestine responsible for nutrient absorption) deteriorate. This atrophy can impair nutrient absorption (malabsorption), potentially causing failure to thrive, characterized by inadequate growth and weight gain.

Individuals with dihydropyrimidinase deficiency, even those without other symptoms, face an increased risk of severe, potentially fatal reactions to fluoropyrimidine drugs, which are used in cancer treatment. Examples of these drugs include 5-fluorouracil and capecitabine. Due to impaired drug breakdown, fluoropyrimidines can accumulate to toxic levels (fluoropyrimidine toxicity), resulting in adverse reactions like gastrointestinal problems, blood disorders, and other symptoms.

Inheritance:

Dihydropyrimidinase deficiency follows an autosomal recessive inheritance pattern. This means that both copies of the responsible gene within each cell must contain mutations for the condition to develop. Individuals with only one copy of the mutated gene are carriers, typically without exhibiting any signs or symptoms of the condition.