Dihydropyrimidine Dehydrogenase Deficiency: Metabolic Disease or Biochemical Phenotype?
| Autor: | Marielle Alders, Rutger Meinsma, J Willomitzer, A. B. P. Van Kuilenburg, Martina Huemer, Judith Meijer, Raoul C.M. Hennekam, Martin Fleger |
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| Přispěvatelé: | Amsterdam Reproduction & Development (AR&D), Human Genetics, Other departments, APH - Quality of Care, Paediatric Genetics, Laboratory Genetic Metabolic Diseases, Amsterdam Gastroenterology Endocrinology Metabolism, ACS - Pulmonary hypertension & thrombosis, University of Zurich, Huemer, Martina |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Microcephaly 610 Medicine & health 1301 Biochemistry Genetics and Molecular Biology (miscellaneous) Article 03 medical and health sciences Dihydropyrimidine dehydrogenase deficiency 0302 clinical medicine Internal medicine Angelman syndrome medicine Dihydropyrimidine dehydrogenase Allele Exome sequencing business.industry medicine.disease Phenotype eye diseases 2712 Endocrinology Diabetes and Metabolism 030104 developmental biology Endocrinology Biochemistry 10036 Medical Clinic 2724 Internal Medicine DPYD business 030217 neurology & neurosurgery |
| Zdroj: | JIMD Reports ISBN: 9783662563588 JIMD reports, 37, 49-54. Springer Berlin |
| ISSN: | 2192-8304 |
| Popis: | Dihydropyrimidine dehydrogenase (DPD) deficiency is an autosomal recessive disorder of pyrimidine metabolism that impairs the first step of uracil und thymine degradation. The spectrum of clinical presentations in subjects with the full biochemical phenotype of DPD deficiency ranges from asymptomatic individuals to severely affected patients suffering from seizures, microcephaly, muscular hypotonia, developmental delay and eye abnormalities.We report on a boy with intellectual disability, significant impairment of speech development, highly active epileptiform discharges on EEG, microcephaly and impaired gross-motor development. This clinical presentation triggered metabolic workup that demonstrated the biochemical phenotype of DPD deficiency, which was confirmed by enzymatic and molecular genetic studies. The patient proved to be homozygous for a novel c.2059-22T>G mutation which resulted in an in-frame insertion of 21 base pairs (c.2059-21_c.2059-1) of intron 16 of DPYD. Family investigation showed that the asymptomatic father was also homozygous for the same mutation and enzymatic and biochemical findings were similar to his severely affected son. When the child deteriorated clinically, exome sequencing was initiated under the hypothesis that DPD deficiency did not explain the phenotype completely. A deletion of the maternal allele on chromosome 15q11.2-13-1 was identified allowing the diagnosis of Angelman syndrome (AS). This diagnosis explains the patient's clinical presentation sufficiently; the influence of DPD deficiency on the phenotype, however, remains uncertain. |
| Databáze: | OpenAIRE |
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