Ijaz Sadaqat, Zahoor Muhammad Yasir, Imran Muhammad, Ramzan Khushnooda, Bhinder Munir Ahmad, Shakeel Hussain, Iqbal Muhammad, Aslam Asim, Shehzad Wasim, Cheema Huma Arshad, Rehman Habib
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J Pediatr Endocrinol Metab. 2017 Oct 26;30(11):1203-1210. doi: 10.1515/jpem-2017-0188.
Fructose-1,6-bisphosphatase (FBPase) deficiency is a rare inherited metabolic disorder characterized by recurrent episodes of hypoglycemia, ketosis and lactic acidosis. FBPase is encoded by FBP1 gene and catalyzes the hydrolysis of fructose-1,6-bisphosphate to fructose-6-phosphate in the last step of gluconeogenesis. We report here FBP1 mutations in nine consanguineous Pakistani families affected with FBPase deficiency.
Nine families having one or two individuals affected with FBPase deficiency were enrolled over a period of 3 years. All FBP1 exonic regions including splicing sites were PCR-amplified and sequenced bidirectionally. Familial cosegregation of mutations with disease was confirmed by direct sequencing and PCR-RFLP analysis.
Three different FBP1 mutations were identified. Each of two previously reported mutations (c.472C>T (p.Arg158Trp) and c.841G>A (p.Glu281Lys)) was carried by four different families. The ninth family carried a novel 4-bp deletion (c.609_612delAAAA), which is predicted to result in frameshift (p.Lys204Argfs*72) and loss of FBPase function. The novel variant was not detected in any of 120 chromosomes from normal ethnically matched individuals.
FBPase deficiency is often fatal in the infancy and early childhood. Early diagnosis and prompt treatment is therefore crucial to preventing early mortality. We recommend the use of c.472C>T and c.841G>A mutations as first choice genetic markers for molecular diagnosis of FBPase deficiency in Pakistan.
果糖-1,6-二磷酸酶（FBPase）缺乏症是一种罕见的遗传性代谢紊乱疾病，其特征为反复出现低血糖、酮症和乳酸性酸中毒。FBPase由FBP1基因编码，在糖异生的最后一步催化果糖-1,6-二磷酸水解为果糖-6-磷酸。我们在此报告9个患有FBPase缺乏症的巴基斯坦近亲家庭中的FBP1突变情况。
在3年时间里招募了9个有1名或2名个体患FBPase缺乏症的家庭。对包括剪接位点在内的所有FBP1外显子区域进行PCR扩增并双向测序。通过直接测序和PCR-RFLP分析确认突变与疾病的家族共分离情况。
鉴定出3种不同的FBP1突变。先前报道的两种突变（c.472C>T（p.Arg158Trp）和c.841G>A（p.Glu281Lys））各被4个不同的家庭携带。第9个家庭携带一种新的4碱基缺失（c.609_612delAAAA），预计会导致移码突变（p.Lys204Argfs*72）并丧失FBPase功能。在120条来自种族匹配的正常个体的染色体中均未检测到这种新变异。
FBPase缺乏症在婴儿期和儿童早期通常是致命的。因此，早期诊断和及时治疗对于预防早期死亡至关重要。我们建议将c.472C>T和c.841G>A突变作为巴基斯坦FBPase缺乏症分子诊断的首选遗传标记。
