Metabolic Laboratory, Department of Clinical Chemistry, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands.
Sanofi Genzyme, Cambridge, Massachusetts, USA.
J Inherit Metab Dis. 2019 Jan;42(1):147-158. doi: 10.1002/jimd.12036.
Transaldolase deficiency (TALDO-D) is a rare autosomal recessive inborn error of the pentose phosphate pathway. Since its first description in 2001, several case reports have been published, but there has been no comprehensive overview of phenotype, genotype, and phenotype-genotype correlation.
We performed a retrospective questionnaire and literature study of clinical, biochemical, and molecular data of 34 patients from 25 families with proven TALDO-D. In some patients, endocrine abnormalities have been found. To further evaluate these abnormalities, we performed biochemical investigations on blood of 14 patients.
Most patients (n = 22) had an early-onset presentation (prenatally or before 1 month of age); 12 patients had a late-onset presentation (3 months to 9 years). Main presenting symptoms were intrauterine growth restriction, dysmorphic facial features, congenital heart disease, anemia, thrombocytopenia, and hepato(spleno)megaly. An older sib of two affected patients was asymptomatic until the age of 9 years, and only after molecular diagnosis was hepatomegaly noted. In some patients, there was gonadal dysfunction with low levels of testosterone and secondary luteinizing hormone (LH) and follicle-stimulating hormone (FSH) abnormalities later in life. This overview provides information that can be helpful for managing patients and counseling families regarding prognosis. Diagnostic guidelines, possible genotype-phenotype correlations, treatment options, and pathophysiological disease mechanisms are proposed.
转醛醇酶缺乏症（TALDO-D）是戊糖磷酸途径中一种罕见的常染色体隐性遗传性先天缺陷。自 2001 年首次描述以来，已经发表了几例病例报告，但尚无对表型、基因型和表型-基因型相关性的全面概述。
我们对 25 个家系的 34 例经证实的 TALDO-D 患者的临床、生化和分子数据进行了回顾性问卷调查和文献研究。在一些患者中发现了内分泌异常。为了进一步评估这些异常，我们对 14 名患者的血液进行了生化研究。
大多数患者（n=22）表现为早发型（产前或 1 月龄前）；12 例表现为晚发型（3 个月至 9 岁）。主要表现症状为宫内生长受限、面部畸形、先天性心脏病、贫血、血小板减少和肝脾肿大。两名受累患者的哥哥/姐姐在 9 岁之前无症状，仅在分子诊断后发现肝肿大。一些患者存在性腺功能障碍，表现为睾酮水平降低以及黄体生成素（LH）和卵泡刺激素（FSH）异常。本综述提供了有助于管理患者和为患者家属提供预后咨询的信息。提出了诊断指南、可能的基因型-表型相关性、治疗选择和病理生理学疾病机制。
