Biochemical abnormalities in a patient with thymidine phosphorylase deficiency with fatal outcome.
Deficiency of the cytosolic enzyme thymidine phosphorylase (TP) causes a multisystem disorder called mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) syndrome. Clinical symptoms are gastrointestinal dysfunction, muscle involvement and neurological deterioration. TP deficiency is biochemically characterised by accumulation of thymidine and deoxyuridine in body fluids and compromised mitochondrial deoxyribose nucleic acid (mtDNA) integrity (depletion and multiple deletions). In this report we describe a patient with the clinical and biochemical features related to the end stage of the disease. Home parenteral nutrition had started to improve the clinical condition and preparations were initiated for stem cell transplantation (SCT) as a last resort treatment. Unfortunately, the patient died during the induction phase of SCT. This report shows that TP deficiency is a severe clinical condition with a broad spectrum of affected tissues. TP deficiency can be easily determined by the measurement of pyrimidine metabolites in body fluids and TP activity in peripheral blood leucocytes. Early detection and treatment may prevent the progress of the clinical symptoms and, therefore, should be considered for inclusion in newborn screening programmes.
Department of Clinical Genetics, Laboratory for Biochemical Genetics, Maastricht University Medical Centre, P Debyelaan 25, 6229 HX, Maastricht, The Netherlands. jaap.bakker@gen.unimaas.nl
Jaap A
JA
Bakker
Patrick
P
Schlesser
Hubert J M
HJ
Smeets
Baudouin
B
Francois
Jörgen
J
Bierau
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000032:analysis; D004252:DNA Mutational Analysis; D018450:Disease Progression; D017809:Fatal Outcome; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D007418:Intestinal Pseudo-Obstruction / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics / Q000628:therapy; D008297:Male; D017237:Mitochondrial Encephalomyopathies / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics / Q000628:therapy; D039141:Muscular Dystrophy, Oculopharyngeal; D009886:Ophthalmoplegia / Q000151:congenital; D016331:Parenteral Nutrition, Home; D010375:Pedigree; D010641:Phenotype; D011379:Prognosis; D012720:Severity of Illness Index; D033581:Stem Cell Transplantation; D013939:Thymidine Phosphorylase / Q000172:deficiency* / Q000235:genetics; D013997:Time Factors; D028361:Mitochondrial Diseases
D015415:Biomarkers; C543750:TYMP protein, human; D013939:Thymidine Phosphorylase