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Transaldolase deficiency: report of 12 new cases and further delineation of the phenotype
Author(s) -
Eyaid Wafaa,
Al Harbi Talal,
Anazi Shamsa,
Wamelink Mirjam M. C.,
Jakobs Cornelis,
Al Salammah Mohammad,
Al Balwi Mohammed,
Alfadhel Majid,
Alkuraya Fowzan S.
Publication year - 2013
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-012-9577-8
Subject(s) - transaldolase , human genetics , hepatosplenomegaly , genetics , missense mutation , biology , consanguinity , genetic heterogeneity , phenotype , disease , sanger sequencing , medicine , pediatrics , bioinformatics , mutation , pentose phosphate pathway , pathology , gene , endocrinology , glycolysis , metabolism
Purpose Transaldolase deficiency is a recently described inborn error of pentose phosphate pathway. We conducted this study to further delineate the associated phenotype. Methods and results We report on 12 new cases representing six families with this metabolic defect that were observed over an 8 year span. None of these cases received the correct diagnosis initially because of significant overlap in the presenting symptoms (growth retardation, dysmorphic features, cutis laxa, congenital heart disease, hepatosplenomegaly, pancytopenia, and bleeding tendency) with a wide range of genetic disorders. However, the consanguineous nature of these families allowed us to pursue autozygome analysis, which highlighted TALDO as the likely candidate gene and sequencing confirmed segregation of a novel homozygous mutation with the disease in all the studied families. Biochemical analysis was also consistent with transaldolase deficiency. Conclusion This study expands the clinical definition of transaldolase deficiency, and adds to its allelic heterogeneity. In addition, we emphasize the diagnostic challenge posed by this rare and pleiotropic metabolic disorder.