Maines Evelina, Gugelmo Giorgia, Maiorana Arianna, Martinelli Diego, Vitturi Nicola, Lenzini Livia, Piccoli Giovanni, Soffiati Massimo, Franceschi Roberto
Division of Pediatrics, Santa Chiara General Hospital, Azienda Provinciale per i Servizi Sanitari, Largo Medaglie d'oro, 9, 38122 Trento, Italy.
Division of Metabolic Diseases, Department of Medicine, Padova University Hospital, Via Nicolò Giustiniani 2, 35121 Padua, Italy.
J Diabetes Metab Disord. 2024 Dec 27;24(1):27. doi: 10.1007/s40200-024-01527-y. eCollection 2025 Jun.
Untreated patients affected by hereditary fructose intolerance (HFI) present an abnormal transferrin (Tf) glycosylation pattern suggestive of N-hypoglycosylation. Analysis of defects in N-glycosylation is possible by analysis of serum sialotransferrin (sialoTf) pattern. The sialoTf profile is a valuable tool to facilitate the diagnosis of HFI. Its role in the monitoring of the diagnosed patients is less clear and debating.
We examined the literature for the role of profile of serum sialoTf isoforms in monitoring HFI patients aiming at (1) providing an up-to-date summary of the available evidences on the impact of sialoTf isoforms in the follow-up of HFI patients; 2) evaluating the multifactorial effect of genotype and age at diagnosis on sialoTf isoforms; 3) assessing the relation between sialoTf isoforms and long-term liver complications. We used the GRADE approach to rank the quality of evidence.
Nine full papers were identified according to our search criteria. Elevated serum carbohydrate-deficient Tf (CDT) fraction, disialoTf and tetrasialoTf/disialoTf ratio, and the asialoTf, tetrasialoTf and pentasialoTf + hexasialoTf isoforms appeared as the most reliable indicators for a follow up. No clear statistical correlation links sialoTf isoforms and liver damage. Age at diagnosis, potentially related to fructose tolerance, does not overtly impact sialoTf isoforms. Strong genotype-phenotype correlation has not been found so far.
There is no consensus about which isoform of sialoTf is more valuable for monitoring HFI patients. No clear correlation links sialoTf isoforms and liver damage, fructose tolerance and genotype. More robust studies are needed to provide conclusive results.
未经治疗的遗传性果糖不耐受（HFI）患者呈现出异常的转铁蛋白（Tf）糖基化模式，提示N-低聚糖基化。通过分析血清唾液酸转铁蛋白（sialoTf）模式可对N-糖基化缺陷进行分析。sialoTf谱是辅助诊断HFI的一项有价值的工具。其在已确诊患者监测中的作用尚不清楚且存在争议。
我们查阅文献以了解血清sialoTf亚型谱在监测HFI患者中的作用，旨在（1）提供关于sialoTf亚型对HFI患者随访影响的现有证据的最新总结；（2）评估诊断时的基因型和年龄对sialoTf亚型的多因素影响；（3）评估sialoTf亚型与长期肝脏并发症之间的关系。我们采用GRADE方法对证据质量进行分级。
根据我们的检索标准，共确定了9篇全文。血清碳水化合物缺乏型Tf（CDT）分数、双唾液酸Tf和四唾液酸Tf/双唾液酸Tf比值以及去唾液酸Tf、四唾液酸Tf和五唾液酸Tf + 六唾液酸Tf亚型似乎是随访的最可靠指标。sialoTf亚型与肝损伤之间没有明确的统计学相关性。诊断时的年龄可能与果糖耐受性有关，但并未明显影响sialoTf亚型。目前尚未发现强的基因型-表型相关性。
关于哪种sialoTf亚型对监测HFI患者更有价值尚无共识。sialoTf亚型与肝损伤、果糖耐受性和基因型之间没有明确的相关性。需要更有力的研究来提供确凿的结果。
