ABSTRACT
Prolidase deficiency is an autosomal recessive disorder that is characterized by considerable inter- and intrafamilial variability in its clinical presentation, ranging from asymptomatic to severe and fatal illness. We report here, for the first time, prenatal diagnosis of prolidase deficiency in a family whose first child was severely affected since birth and died at an early age. However, unexpectedly, the parents decided to continue the second pregnancy, which produced a full-term, healthy-appearing baby. The diagnosis of severe prolidase deficiency was confirmed in the baby's leukocytes. At age 4 months the baby is asymptomatic. Since the clinical severity of the disorder cannot be predicted, genetic counselling remains problematic despite the feasibility of prenatal diagnosis.
Subject(s)
Amino Acid Metabolism, Inborn Errors/diagnosis , Amniocentesis , Dipeptidases/deficiency , Fetal Diseases/diagnosis , Genetic Diseases, Inborn/diagnosis , Amino Acid Metabolism, Inborn Errors/genetics , Amino Acids/blood , Arabs/genetics , Consanguinity , Dipeptidases/genetics , Dipeptidases/metabolism , Fatal Outcome , Female , Fetal Diseases/enzymology , Genetic Diseases, Inborn/enzymology , Humans , Infant, Newborn , Israel , Jews/genetics , Leukocytes/enzymology , PrognosisSubject(s)
Amidohydrolases/antagonists & inhibitors , Lipid Metabolism, Inborn Errors/enzymology , Nervous System Diseases/enzymology , Propionates/pharmacology , Adult , Amidohydrolases/metabolism , Chromatography, High Pressure Liquid , Female , Humans , Infant, Newborn , Intellectual Disability/genetics , Lipid Metabolism, Inborn Errors/genetics , Liver/drug effects , Liver/enzymology , Male , Nervous System Diseases/genetics , Propionates/blood , Propionates/metabolism , Pyrimidines/metabolismABSTRACT
Recent findings suggest that inborn errors of pyrimidine catabolism are less rare than generally assumed. We propose a complete set of diagnostic methods for these disorders, suitable for the clinical chemistry laboratory, and present relevant reference data. Applications of thin-layer chromatography, high-performance liquid chromatography, and conventional cation-exchange amino acid analysis lead to detection of various defects in pyrimidine degradation, including the recently described deficiencies of dihydropyrimidine dehydrogenase and dihydropyrimidinase. We also illustrate the potential of the methods to analyze for the catabolites expected to be increased in the urine of patients with ureidopropionase deficiency. Possible pitfalls in the diagnosis and ways to prevent misdiagnosis are demonstrated. The methods offer possibilities for clinical chemistry laboratories to extend their diagnostic capacity to the new area of pyrimidine degradation defects.
