Department of General Pediatrics, Adolescent Medicine and Neonatology, Medical Center-University of Freiburg, 79106 Freiburg, Germany.
Pediatric Unit, Department of Medical and Surgical Sciences, Regional Center for Expanded Newborn Screening, S. Orsola-Malpighi University Hospital, 40138 Bologna, Italy.
Genes (Basel). 2021 Nov 10;12(11):1785. doi: 10.3390/genes12111785.
Fanconi-Bickel syndrome (FBS) is a very rare but distinct clinical entity with the combined features of hepatic glycogen storage disease, generalized proximal renal tubular dysfunction with disproportionately severe glucosuria, and impaired galactose tolerance. Here, we report five cases (out of 93 diagnosed in our lab) with pathogenic variants on both () alleles. They come from 3 families and presented with an exceptionally mild clinical course. This course was correlated to data from old and most recent expression and transport studies in oocytes. genotype in patients 1 and 2 was p.[153_4delLI];[P417R] with the first variant exhibiting normal membrane expression and partially retained transport activity (5.8%) for 2-deoxyglucose. In patient 3, the very first variant ever detected (p.V197I) was found, but for the first time it was present in a patient in the homozygous state. This variant had also shown unaffected membrane expression and remarkable residual activity (8%). The genotype in patient 4, p.[153_4delLI];[(E440A)], again included the 2-amino-acid deletion with residual transporter function, and patient 5 is the first found to be homozygous for this variant. Our results provide further evidence for a genotype-phenotype correlation in patients with variants; non-functional variants result in the full picture of FBS while dysfunctional variants may result in milder presentations, even glucosuria only, without other typical signs of FBS.
范可尼-比克尔综合征（FBS）是一种非常罕见但独特的临床实体，具有肝糖原贮积病、广泛近端肾小管功能障碍伴葡萄糖尿不成比例严重、以及半乳糖耐量受损等特征。在此，我们报告了 5 例（在我们实验室诊断的 93 例中）在 （）等位基因上均存在致病变异的病例。它们来自 3 个家系，表现出异常轻微的临床病程。这一病程与我们在卵母细胞中进行的旧和最近的表达和转运研究数据相关。患者 1 和 2 的 基因型为 p.[153_4delLI];[P417R]，第一个变异体表现出正常的膜表达和部分保留的 2-脱氧葡萄糖转运活性（5.8%）。在患者 3 中，首次发现了非常早期的 变异体（p.V197I），但这是首次在纯合状态下的患者中发现。该变异体也表现出正常的膜表达和显著的残留活性（8%）。患者 4 的基因型为 p.[153_4delLI];[(E440A)]，再次包含氨基酸缺失和残留的转运体功能，患者 5 是首个被发现该变异体纯合的病例。我们的结果为 变异患者的基因型-表型相关性提供了进一步的证据；无功能变异体导致出现完整的 FBS 表现，而功能失调的变异体可能导致更轻微的表现，甚至只有葡萄糖尿，而没有 FBS 的其他典型体征。
