Severe Triosephosphate Isomerase Deficiency in Homozygous Twin Sisters: A Rare Cause of Neonatal Hemolytic Anemia and Neurometabolic Disorder

Abstract

Triosephosphate isomerase (TPI) deficiency is an autosomal recessive glycolytic enzymopathy that usually manifests during infancy. It is characterized by chronic hemolytic anemia beginning in the neonatal period, increased susceptibility to infectious diseases, and, in particular, progressive neurological deterioration that typically leads to death within the first years of life. We present the diagnostic evaluation and clinical course of monozygotic female twins who presented with chronic hemolytic anemia. Routine assessments for hemolysis were normal in both sisters, including the direct Coombs test, hemoglobin (Hb) electrophoresis, and enzymatic assays for pyruvate kinase and glucose-6-phosphate dehydrogenase (G6PD). At 10 months of age, the first twin was hospitalized with severe pneumonia and abnormal movements. Molecular testing confirmed the diagnosis of TPI deficiency in both twins. The other twin developed psychomotor regression at 13 months of age. In patients with unexplained chronic hemolysis, TPI deficiency must be considered, especially when neuromotor disorders develop. Interestingly, despite sharing the same mutation, neurological manifestations varied between the affected twins. Identification of the index case enables genetic counseling, and offers the possibility of prenatal diagnosis in future pregnancies.