*Metabolic Disease Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer †Genetics Institute, Assaf Harofeh Medical Center, Zerifin, Israel ‡University of Istanbul, Cerrahpasa Medical Faculty, Department of Pediatrics, Division of Metabolic Diseases, Istanbul, Turkey §Department of Biological Resources Engineering, University of Maryland, College Park ||Pediatric Stem Cell Research Institute, Edmond & Lily Safra Children's Hospital, Sheba Medical Center ¶Pediatric Gastroenterology and Nutrition Unit, Edmond and Lily Safra Children's Hospital.
J Pediatr Gastroenterol Nutr. 2014 Jan;58(1):57-60. doi: 10.1097/MPG.0000000000000114.
Glucose galactose malabsorption (GGM) is a rare autosomal recessive disorder characterized by life-threatening osmotic diarrhea at infancy. When the intake of the offending sugars (namely, glucose, galactose and lactose) is ceased, the diarrhea promptly stops. Mutations in the SLC5A1 gene, encoding the sodium-glucose co-transporter located in the brush border of enterocytes, have been shown to cause the disease. More than 300 subjects of diverse origin have been reported worldwide, most of whom are a result of a consanguineous union. We examined 6 patients from 4 families presenting with complaints consistent with GGM and responsive to the appropriate fructose-based diet. Genomic DNA of the patients was polymerase chain reaction amplified for each of the 15 exons of the SLC5A1 gene and analyzed by nucleotide sequencing. The analysis lead to the identification of 2 novel mutations: a 1915 del C mutation, a frameshift mutation leading to a premature stop at codon 645; and a substitution missense mutation of T to C on nucleotide 947 (exon 9) causing a L316P substitution. In addition, G426R and C255W mutations previously described were identified; in both cases, the patients were shown to be homozygous and their parents heterozygous for the mutation. Of note, additional patients who underwent a similar evaluation at our center for suspected GGM did not show mutations in the SLC5A1 gene. Because the latter did not previously undergo a diagnostic algorithm in full, for instance, one that may consist of a glucose breath hydrogen test and an empiric attempt of a dietary switch to galactomin, we suggest that molecular genotyping of such patients should only follow such appropriate clinical evaluation.
葡萄糖-半乳糖吸收不良症（GGM）是一种罕见的常染色体隐性遗传病，其特征为婴儿期危及生命的渗透性腹泻。当停止摄入引起疾病的糖（即葡萄糖、半乳糖和乳糖）时，腹泻会立即停止。SLC5A1 基因的突变，该基因编码位于肠上皮细胞刷状缘的钠-葡萄糖共转运蛋白，已被证明可导致该疾病。全世界已经报告了超过 300 名来自不同种族的患者，其中大多数是近亲结婚的结果。我们检查了来自 4 个家庭的 6 名患者，他们表现出与 GGM 一致的症状，并对果糖基饮食有反应。对每位患者的 SLC5A1 基因的 15 个外显子进行聚合酶链反应扩增，并进行核苷酸测序分析。分析导致鉴定出 2 种新的突变：1915delC 突变，导致提前在密码子 645 处终止的移码突变；以及核苷酸 947（外显子 9）处 T 到 C 的取代错义突变，导致 L316P 取代。此外，还鉴定出先前描述的 G426R 和 C255W 突变；在这两种情况下，患者均被证实为纯合子，其父母为该突变的杂合子。值得注意的是，在我们中心接受疑似 GGM 类似评估的其他患者并未在 SLC5A1 基因中发现突变。因为后者之前并未完全进行诊断算法，例如，可能包括葡萄糖呼吸氢试验和经验性尝试改用半乳糖素的饮食转换，因此我们建议仅在进行适当的临床评估后对这些患者进行分子基因分型。
