Biochemical abnormalities in a patient with thymidine phosphorylase deficiency with fatal outcome

J Inherit Metab Dis. 2010 Dec;33 Suppl 3(Suppl 3):S139-43. doi: 10.1007/s10545-010-9049-y. Epub 2010 Feb 12.

Abstract

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.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers / analysis
  • DNA Mutational Analysis
  • Disease Progression
  • Fatal Outcome
  • Female
  • Genetic Predisposition to Disease
  • Genetic Testing
  • Humans
  • Intestinal Pseudo-Obstruction / diagnosis
  • Intestinal Pseudo-Obstruction / enzymology*
  • Intestinal Pseudo-Obstruction / genetics
  • Intestinal Pseudo-Obstruction / therapy
  • Male
  • Mitochondrial Encephalomyopathies / diagnosis
  • Mitochondrial Encephalomyopathies / enzymology*
  • Mitochondrial Encephalomyopathies / genetics
  • Mitochondrial Encephalomyopathies / therapy
  • Muscular Dystrophy, Oculopharyngeal
  • Ophthalmoplegia / congenital
  • Parenteral Nutrition, Home
  • Pedigree
  • Phenotype
  • Prognosis
  • Severity of Illness Index
  • Stem Cell Transplantation
  • Thymidine Phosphorylase / deficiency*
  • Thymidine Phosphorylase / genetics
  • Time Factors

Substances

  • Biomarkers
  • TYMP protein, human
  • Thymidine Phosphorylase

Supplementary concepts

  • Visceral myopathy familial external ophthalmoplegia

Associated data

  • OMIM/OMIM603041
  • RefSeq/NM_001953