If a patient is found to have a partial DPD deficiency, how is chemotherapy dosing adjusted?

For heterozygous carriers, many oncologists start with a 50 % dose reduction of the fluoropyrimidine and then titrate based on tolerance; some use alternative non‑fluoropyrimidine regimens altogether.

Is DPD deficiency inherited, and can family members be tested?

DPD deficiency follows an autosomal recessive pattern; if a pathogenic DPYD variant is identified, first‑degree relatives can be offered genetic testing to guide future chemotherapy decisions.

Should every cancer patient be tested for DPD deficiency before receiving 5‑fluorouracil or capecitabine?

Guidelines recommend pre‑treatment DPD screening—either genotyping for common DPYD variants or phenotyping with a uracil test—especially for colorectal, breast, or head‑and‑neck cancers where fluoropyrimidines are standard.

What symptoms indicate a severe fluoropyrimidine toxicity that requires emergency care?

Rapid onset of severe mouth sores, profuse diarrhea, fever with neutropenia, bleeding from low platelets, or sudden skin changes on palms/soles (hand‑foot syndrome) should prompt immediate hospitalization.

Dihydropyrimidine Dehydrogenase Deficiency

Dihydropyrimidine dehydrogenase deficiency is a genetic condition ranging from asymptomatic to severe neurological impairment, which also causes life-threatening toxic reactions to certain cancer drugs.

Overview & Symptoms

Dihydropyrimidine dehydrogenase deficiency is a disorder characterized by a wide range of severity. Some individuals experience severe neurological problems, while others show no signs or symptoms.

Severe Infantile-Onset Form

In people with severe dihydropyrimidine dehydrogenase deficiency, the disorder becomes apparent in infancy. Affected individuals have neurological problems, including:

Recurrent seizures (epilepsy)
Intellectual disability
A small head size (microcephaly)
Increased muscle tone (hypertonia)
Delayed development of motor skills, such as walking
Autistic behaviors that affect communication and social interaction

Asymptomatic Form & Fluoropyrimidine Toxicity

Some individuals are asymptomatic and may only be identified through laboratory testing. However, all individuals with dihydropyrimidine dehydrogenase deficiency—including those who otherwise exhibit no symptoms—are vulnerable to severe, potentially life-threatening toxic reactions to cancer drugs called fluoropyrimidines (such as 5-fluorouracil and capecitabine). Because these drugs are not broken down efficiently, they build up to toxic levels (fluoropyrimidine toxicity), causing:

Severe inflammation and ulceration of the digestive tract lining (mucositis), leading to mouth sores, abdominal pain, bleeding, nausea, vomiting, and diarrhea
Low numbers of white blood cells (neutropenia), increasing infection risk
Low numbers of platelets (thrombocytopenia), which impairs blood clotting and can lead to abnormal bleeding (hemorrhage)
Redness, swelling, numbness, and peeling of the skin on the palms and soles (hand-foot syndrome)
Shortness of breath
Hair loss

Frequency

Severe dihydropyrimidine dehydrogenase deficiency with early-onset neurological symptoms is a rare disorder of unknown prevalence. However, between 2 and 8 percent of the general population may be vulnerable to toxic reactions to fluoropyrimidine drugs due to otherwise asymptomatic dihydropyrimidine dehydrogenase deficiency.

Causes & Genetic Factors

Dihydropyrimidine dehydrogenase deficiency is caused by mutations in the DPYD gene. This gene provides instructions for making an enzyme called dihydropyrimidine dehydrogenase, which is involved in the breakdown of molecules called uracil and thymine.

Uracil and thymine are pyrimidines, which are a type of nucleotide (the building blocks of DNA, RNA, and energy-serving molecules like ATP and GTP). Mutations in the DPYD gene result in a lack of functional dihydropyrimidine dehydrogenase, interfering with the breakdown of uracil and thymine. This leads to excess quantities of these molecules in the blood, urine, and cerebrospinal fluid. Mutations causing a complete absence of the enzyme generally lead to more severe symptoms than those causing a partial deficiency.

Inheritance

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Depending on the severity of the mutations, individuals with two mutated copies of the DPYD gene may show severe symptoms or remain asymptomatic but at risk for drug toxicity.

The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. However, individuals carrying only one mutated copy of the DPYD gene in each cell may still experience toxic reactions to fluoropyrimidine drugs.

Other Names for This Condition

Dihydropyrimidinuria
DPD deficiency
Familial pyrimidemia
Hereditary thymine-uraciluria