Bhai Pratibha, Bijarnia-Mahay Sunita, Puri Ratna D, Saxena Renu, Gupta Deepti, Kotecha Udhaya, Sachdev Anil, Gupta Dhiren, Vyas Vyomesh, Agarwal Divya, Jain Vivek, Bansal Rajeev K, Kumar Tapisha G, Verma Ishwar Chander
Institute of Medical Genetics, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, India.
Ann Hum Genet. 2018 Sep;82(5):309-317. doi: 10.1111/ahg.12256. Epub 2018 May 18.
Fructose-1, 6-bisphosphatase deficiency is an autosomal recessive disorder of gluconeogenesis caused by genetic defect in the FBP1 gene. It is characterized by episodic, often life-threatening metabolic acidosis, liver dysfunction, and hyperlactatemia. Without a high index of suspicion, it may remain undiagnosed with devastating consequences. Accurate diagnosis can be achieved either by enzyme assay or gene studies. Enzyme assay requires a liver biopsy and is tedious, invasive, expensive, and not easily available. Therefore, genetic testing is the most appropriate method to confirm the diagnosis. Molecular studies were performed on 18 suspected cases presenting with episodic symptoms. Seven different pathogenic variants were identified. Two common variants were noted in two subpopulations from the Indian subcontinent; p.Glu281Lys (E281K) occurred most frequently (in 10 patients) followed by p.Arg158Trp (R158W, in 4 patients). Molecular analysis confirmed the diagnosis and helped in managing these patients by providing appropriate genetic counseling. In conclusion, genetic studies identified two common variants in the Indian subcontinent, thus simplifying the diagnostic algorithm in this treatable disorder.
果糖-1,6-二磷酸酶缺乏症是一种由FBP1基因的遗传缺陷引起的糖异生的常染色体隐性疾病。其特征为发作性、常危及生命的代谢性酸中毒、肝功能障碍和高乳酸血症。如果没有高度的怀疑指数，该病可能仍未被诊断出来，从而导致灾难性后果。通过酶测定或基因研究可实现准确诊断。酶测定需要进行肝活检，且繁琐、有创、昂贵且不易进行。因此，基因检测是确诊的最合适方法。对18例表现为发作性症状的疑似病例进行了分子研究。鉴定出7种不同的致病变异。在来自印度次大陆的两个亚群中发现了两种常见变异；p.Glu281Lys（E281K）出现频率最高（10例患者），其次是p.Arg158Trp（R158W，4例患者）。分子分析确诊了疾病，并通过提供适当的遗传咨询帮助管理这些患者。总之，基因研究在印度次大陆发现了两种常见变异，从而简化了这种可治疗疾病的诊断算法。
