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Dihydropyrimidine Dehydrogenase Deficiency

DPD Deficiency


Presentation

  • In the present study, we demonstrated that only a slightly decreased concentration of beta-alanine was present in the urine and plasma, whereas normal levels of beta-alanine were present in the cerebrospinal fluid of patients with a DPD deficiency.[ncbi.nlm.nih.gov]
  • Anoxic stress may have contributed to the clinical presentation and brain findings in this case.[ncbi.nlm.nih.gov]
  • We also present the complex management problems that have to be anticipated in treating such systemically compromised patients.[ncbi.nlm.nih.gov]
  • DPD deficiency is a pharmacogenetic syndrome which is also present in the Indian population. If undiagnosed, the DPD deficiency can lead to death.[ncbi.nlm.nih.gov]
  • We present the clinical and biochemical features of a boy with dihydropyrimidine dehydrogenase deficiency, which seem to underline a disease entity of developmental retardation, epilepsy and muscular hypertonia.[ncbi.nlm.nih.gov]
Hypoventilation
  • To further understanding of the spectrum of brain abnormalities associated with DPD deficiency, we report a 17-month-old girl, born to a consanguineous Pakistani couple, who had a history of encephalopathy, prolonged hypoventilation, developmental delay[ncbi.nlm.nih.gov]
  • Previously, the c.1651G A mutation was detected in the parents of a deceased DPD-deficient patient who had a history of epileptic manifestation in earlier childhood, encephalopathy, prolonged hypoventilation, developmental delay and failure to thrive,[karger.com]
Aspiration
  • At age 15 months, she was hospitalized for aspiration pneumonia and seizures, and also manifested hepatosplenomegaly.[ncbi.nlm.nih.gov]
Hepatosplenomegaly
  • At age 15 months, she was hospitalized for aspiration pneumonia and seizures, and also manifested hepatosplenomegaly.[ncbi.nlm.nih.gov]
Lower Lid Ectropion
  • A bilateral cicatrizing lower lid ectropion, bilateral upper lid shortening, cicatrizing and sclerosing facial skin changes occurred in an 80-year-old male, undergoing preoperative chemoradiotherapy, incorporating Capecitabine, an oral 5-FU prodrug for[ncbi.nlm.nih.gov]
Suggestibility
  • Another approach is to determine DPD activity in peripheral blood mononuclear cells, with low activity suggesting an increased risk of toxicity.[ncbi.nlm.nih.gov]
  • It has been suggested that an altered homoeostasis of beta-alanine underlies some of the clinical abnormalities encountered in patients with a DPD deficiency.[ncbi.nlm.nih.gov]
  • Current research suggests that nearly 8% of the population has at least partial DPD deficiency.[en.wikipedia.org]
  • We describe a 1-year-old Tunisian girl with a dramatic onset of neurological symptoms suggesting the possible triggering role of environmental factors.[ncbi.nlm.nih.gov]
  • The authors suggest that MIL is a direct result of 5-FU chemotherapy and that patients with dihydropyrimidine dehydrogenase deficiency are at increased risk for this and other toxic effects of 5-FU.[ncbi.nlm.nih.gov]
Psychomotor Retardation
  • We report a case of an 8-year-old girl with psychomotor retardation and mild course of the disease. Analysis of urine showed strongly elevated levels of uracil and thymine, and no DPD activity could be detected in peripheral blood mononuclear cells.[ncbi.nlm.nih.gov]
  • In a patient presenting with convulsions, psychomotor retardation and Reye like syndrome, strongly elevated levels of uracil and thymine were detected in urine. No DPD activity could be detected in peripheral blood mononuclear cells.[ncbi.nlm.nih.gov]
  • Haploinsufficiency of NTNG1, LPPR4, GPSM2, COL11A1 and VAV3 might have contributed to the severe psychomotor retardation and unusual craniofacial features in this patient.[ncbi.nlm.nih.gov]
  • {menu2} DIHYDROPYRIMIDINE DEHYDROGENASE DEFICIENCY (DPD) Bakker HD Dihydropyrimidine dehydrogenase deficiency presenting with psychomotor retardation and ocular abnormalities, 1994 , P. 640-641 et al.[metagene.de]
  • retardation in the first Polish patient. ( 19081848 ) Mazur A....Van Kuilenburg A.B. 2008 42 5-Fluorouracil-related severe toxicity: a comparison of different methods for the pretherapeutic detection of dihydropyrimidine dehydrogenase deficiency. ( 17064846[malacards.org]
Psychomotor Retardation
  • We report a case of an 8-year-old girl with psychomotor retardation and mild course of the disease. Analysis of urine showed strongly elevated levels of uracil and thymine, and no DPD activity could be detected in peripheral blood mononuclear cells.[ncbi.nlm.nih.gov]
  • In a patient presenting with convulsions, psychomotor retardation and Reye like syndrome, strongly elevated levels of uracil and thymine were detected in urine. No DPD activity could be detected in peripheral blood mononuclear cells.[ncbi.nlm.nih.gov]
  • Haploinsufficiency of NTNG1, LPPR4, GPSM2, COL11A1 and VAV3 might have contributed to the severe psychomotor retardation and unusual craniofacial features in this patient.[ncbi.nlm.nih.gov]
  • {menu2} DIHYDROPYRIMIDINE DEHYDROGENASE DEFICIENCY (DPD) Bakker HD Dihydropyrimidine dehydrogenase deficiency presenting with psychomotor retardation and ocular abnormalities, 1994 , P. 640-641 et al.[metagene.de]
  • retardation in the first Polish patient. ( 19081848 ) Mazur A....Van Kuilenburg A.B. 2008 42 5-Fluorouracil-related severe toxicity: a comparison of different methods for the pretherapeutic detection of dihydropyrimidine dehydrogenase deficiency. ( 17064846[malacards.org]
Anger
Hyperactivity
  • […] metabolism, systemic and rheumatological Phenotypes Agenesis of corpus callosum ; Autism ; Autosomal recessive inheritance ; Cerebral atrophy ; Coloboma ; Delayed speech and language development ; Failure to thrive ; Generalized hypotonia ; Growth delay ; Hyperactivity[mousephenotype.org]
Delayed Speech and Language Development
  • speech and language development ; Failure to thrive ; Generalized hypotonia ; Growth delay ; Hyperactivity ; Hypertonia ; Intellectual disability ; Lethargy ; Microcephaly ; Microphthalmia ; Motor delay ; Muscular hypotonia ; Nystagmus ; Optic atrophy[mousephenotype.org]
Hyperactivity
  • […] metabolism, systemic and rheumatological Phenotypes Agenesis of corpus callosum ; Autism ; Autosomal recessive inheritance ; Cerebral atrophy ; Coloboma ; Delayed speech and language development ; Failure to thrive ; Generalized hypotonia ; Growth delay ; Hyperactivity[mousephenotype.org]
Gait Ataxia
  • Neurologic examination on October 22, 1998, was normal except for mild gait ataxia, with the patient completing three of five serial seven calculations and recalling two of three objects at 5 minutes.[neurology.org]

Workup

Gliosis
  • Cranial magnetic resonance imaging at 14 months indicated severe hypomyelination with gliosis. Her basal ganglia were also involved.[ncbi.nlm.nih.gov]

Treatment

  • We also discuss whether screening for DPD deficiency is warranted to identify patients at risk for severe toxicities from 5-FU treatment.[ncbi.nlm.nih.gov]
  • To date, screening of patients for the presence of a DPD deficiency prior to the treatment is not yet routinely performed.[ncbi.nlm.nih.gov]
  • For patients with complete DPD deficiency, fluoropyrimidine-treatment has generally been discouraged.[ncbi.nlm.nih.gov]
  • After the first cycle of chemotherapy, the patient manifested grade 2 mucositis and febrile neutropenia, and when her treatment was subsequently continued with doxifluridine she developed severe mucositis and febrile neutropenia.[ncbi.nlm.nih.gov]

Prognosis

  • Prognosis - Dihydropyrimidine dehydrogenase deficiency Not supplied. Treatment - Dihydropyrimidine dehydrogenase deficiency Not supplied. Resources - Dihydropyrimidine dehydrogenase deficiency Not supplied.[checkorphan.org]
  • This recommendation is further confounded by the therapeutic dilemma that tumors with low DPD levels are associated with improved 5-FU sensitivity 30,31 and better prognosis than high level DPD tumors. 32,33 Capecitabine offers an improved safety profile[pjms.com.pk]
  • Active carcinoma affect to prognosis. 18. Congenial hemorrhage or clotting abnormality 19. Current serious, uncontrolled infection or current known HIV infection. 20.[upload.umin.ac.jp]

Etiology

  • DPD deficiency might be an etiological factor in the clinical picture of these patients. An autosomal recessive mode of inheritance of this deficiency was found.[ncbi.nlm.nih.gov]
  • We evaluated the importance of DPD deficiency, gender and the presence of the IVS14 1G A mutation in the etiology of 5-FU toxicity. In 61% of cases, decreased DPD activity could be detected in peripheral blood mononuclear cells.[ncbi.nlm.nih.gov]
  • In conclusion, a partial DPD deficiency appears to play an important role in the etiology of 5FU-associated toxicity.[clincancerres.aacrjournals.org]
  • Her CBC revealed leucopenia (1.600 10 9 /l), neutropenia (0.421 10 9 /l), and thrombocytopenia (41 10 9 /l), and after admission, the patient also manifested a fever of unidentified etiology.[kjim.org]
  • On the one hand, the differential diagnosis of a skin reaction in a cancer patient with chemotherapy treatment includes a large number of etiologies: toxicity by the drug itself, infections, paraneoplastic syndromes, tumour dissemination, or nutritional[omicsonline.org]

Epidemiology

  • Future epidemiological studies would be helpful to determine the prevalence of DPD deficiency among racial and ethnic groups, allowing for the optimization of 5-FU chemotherapy.[ncbi.nlm.nih.gov]
  • Epidemiology Current research suggests that nearly 8% of the population has at least partial DPD deficiency.[ipfs.io]
  • […] convulsive disorders of variable clinical expression,motor and mental retardation,mild or quite severe,hereditary and sensitivity to fluorouracyl in heterozygotes Relevant External Links for DPYD Genetic Association Database (GAD) DPYD Human Genome Epidemiology[genecards.org]
  • Future epidemiological studies would be helpful to determine the prevalence of DPD deficiency among racial and ethnic groups, allowing for the optimization of 5-FU chemotherapy. References Lu Z, Zhang R, Carpenter JT, Diasio RB.[joplink.net]
Sex distribution
Age distribution

Pathophysiology

  • […] variants associated with decreased or absent DPD enzyme activity Genetics Test Information Provides information that may help with selection of the correct genetic test or proper submission of the test request Clinical Information Discusses physiology, pathophysiology[mayomedicallaboratories.com]

Prevention

  • With the ever-increasing number of patients with cancer likely to be treated with fluoropyrimidines, predicting and preventing the occurrence of such toxicities is now a major issue in clinical oncology.[ncbi.nlm.nih.gov]
  • Abstract A rapid yet reliable chemical diagnosis for dihydropyrimidine dehydrogenase (DHPD) deficiency, and possibly dihydropyrimidinase (DHP) deficiency in cancer patients, prior to therapy with pyrimidine analogues such as 5-fluorouracil, is desired for prevention[ncbi.nlm.nih.gov]
  • Overview Dihydropyrimidine dehydrogenase deficiency: A metabolic error where a deficiency of an enzyme called dihydropyrimidine dehydrogenase prevents the normal metabolism of certain proteins.[checkorphan.org]
  • Our goal is to provide information that can be used to develop effective means to prevent or reduce the severity of this metabolic condition. .[mayo.edu]
  • This could be the first indication that there is a potential risk for DPD Deficiency and further blood tests before chemotherapy could prevent severe 5-FU toxicity.[strongmom.org]

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