Abstract Fructose-1,6-bisphosphatase (FBPase) deficiency is a rare inborn error of fructose metabolism caused by pathogenic variants in the FBP1 gene. As gluconeogenesis is affected, catabolic episodes can induce ketotic hypoglycemia in patients. FBP1 analysis is the most commonly used approach for the diagnosis of this disorder. Herein, a Brazilian patient is reported. The proband, a girl born to a consanguineous couple, presented with severe hypoglycemia crisis in the neonatal period. At the age 17 months, presented a new crisis accompanied by metabolic acidosis associated with a feverish episode. Genetic analysis was performed by next-generation sequencing (NGS), identifying the NM_000507.3:c.611_614del variant in homozygosis in the FBP1 gene. In silico analysis and 3D modeling were performed, suggesting that this variant is associated with a loss of sites for substrate and Mg2+ binding and for posttranslational modifications of FBPase. The c.611_614del variant is located in a repetitive region of the FBP1 gene that appears to be a hotspot for mutational events. This frameshift creates a premature termination codon in the last coding exon which escapes the nonsense-mediated decay mechanism, according to in silico analysis. This variant results in an intrinsically disordered protein with loss of substrate recognition and post-translational modification sites.

中文翻译：

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果糖1，，6-双磷酸酶缺乏症和p。（Lys204ArgfsTer72）变体

摘要果糖-1,6-双磷酸酶（FBPase）缺乏症是由FBP1基因的致病变异引起的果糖代谢的先天性错误。由于糖异生作用受到影响，分解代谢发作可诱发患者的酮症性低血糖症。FBP1分析是诊断该疾病的最常用方法。在此，报道了一名巴西患者。该先证者是一对近亲夫妇所生的女孩，在新生儿期出现严重的低血糖危机。在17个月大时，出现了新的危机，伴有伴随发烧发作的代谢性酸中毒。通过下一代测序（NGS）进行了遗传分析，鉴定了FBP1基因纯合性中的NM_000507.3：c.611_614del变体。进行了计算机分析和3D建模，提示该变体与底物和Mg2 +结合位点的缺失以及FBPase的翻译后修饰有关。c.611_614del变体位于FBP1基因的重复区域中，该区域似乎是突变事件的热点。根据计算机分析，此移码会在最后一个编码外显子中产生一个过早的终止密码子，从而逃避了无意义的介导的衰变机制。该变体导致内在无序的蛋白质，其具有底物识别和翻译后修饰位点的损失。根据计算机分析，此移码会在最后一个编码外显子中产生一个过早的终止密码子，从而逃避了无意义的介导的衰变机制。该变体导致内在无序的蛋白质，其具有底物识别和翻译后修饰位点的损失。根据计算机分析，此移码会在最后一个编码外显子中产生一个过早的终止密码子，从而逃避了无意义的介导的衰变机制。该变体导致内在无序的蛋白质，其具有底物识别和翻译后修饰位点的损失。