Department of Pediatrics, Genetics division, King AbdulAziz Medical City, Riyadh, Saudi Arabia,
J Inherit Metab Dis. 2013 Nov;36(6):997-1004. doi: 10.1007/s10545-012-9577-8. Epub 2013 Jan 12.
Transaldolase deficiency is a recently described inborn error of pentose phosphate pathway. We conducted this study to further delineate the associated phenotype.
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.
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.
转醛醇酶缺乏症是戊糖磷酸途径中一种新发现的先天性代谢缺陷。本研究旨在进一步阐明其相关表型。
我们报告了 12 例新病例，代表了 6 个有此代谢缺陷的家系，这些家系在 8 年的时间跨度内被观察到。由于临床表现（生长迟缓、畸形特征、皮肤松弛、先天性心脏病、肝脾肿大、全血细胞减少和出血倾向）与广泛的遗传疾病存在显著重叠，这些病例最初都没有得到正确的诊断。然而，这些家系的近亲婚配性质使我们能够进行自交系分析，这突出了 TALDO 作为可能的候选基因，测序也证实了所有研究家系中疾病的新型纯合突变的分离。生化分析也与转醛醇酶缺乏症一致。
本研究扩展了转醛醇酶缺乏症的临床定义，并增加了其等位基因异质性。此外，我们强调了这种罕见且多效性代谢紊乱带来的诊断挑战。
