背景:儿童低磷血症是一种罕见的疾病,可能是由吸收不良引起的,恶性肿瘤,或遗传因素。长期的低磷酸盐血症会导致生长受损和X线征象。
方法:我们对一名血浆磷酸盐浓度反复低(低于0.60mmol/L)的青春期男孩进行了详细的临床和遗传评估,增长失败。
结果:14岁时,患者出现生长减速和青春期延迟。生化显示尿磷酸盐丢失增加导致低磷酸盐血症;肾功能和维生素D状态正常。放射学照片显示干phy端轻度改变。已知遗传性低磷酸盐血症的基因组为阴性。三联外显子组分析,然后进行Sanger测序,鉴定了PRFP8基因中的致病性杂合从头停止增益变体,c.5548C>Tp.(Arg1850*)。,在保守的RNaseH同源结构域中。PRPF8编码前RNA蛋白8,其在RNA加工中起作用。杂合PRPF8变体与色素性视网膜炎和神经发育障碍有关,但与磷酸盐代谢无关。患者接受了生长激素(GH)刺激试验,证实GH缺乏。头颅MRI提示蝶鞍部分空。GH治疗在15年开始。令人惊讶的是,GH治疗期间磷酸盐代谢正常化,提示低磷血症至少部分继发于生长激素缺乏.
结论:结论:对患有严重的长期低磷酸盐血症的青少年进行的评估显示,垂体发育缺陷与PRFF8的停止增益变异相关.GH治疗可缓解低磷血症。病理性PRFP8变异可能导致垂体发育异常;然而,其在磷酸盐代谢中的作用仍不确定。
BACKGROUND: Childhood hypophosphatemia is a rare condition and may be caused by malabsorption, malignancies, or genetic factors. Prolonged hypophosphatemia leads to impaired growth and radiographic signs of rickets.
METHODS: We performed a detailed clinical and genetic evaluation of an adolescent boy with repeatedly low plasma phosphate concentrations (below 0.60 mmol/L) and growth failure.
RESULTS: At 14 years, the patient presented with decelerating growth and delayed puberty. Biochemistry showed hypophosphatemia due to increased urinary phosphate loss; kidney function and vitamin D status were normal. Radiographs showed mild metaphyseal changes. A gene panel for known genetic hypophosphatemia was negative. Trio exome analysis followed by Sanger sequencing identified a pathogenic heterozygous de novo stop-gain variant in PRPF8 gene, c.5548C>T p.(Arg1850*), in the conserved RNase H homology domain. PRPF8 encodes the pre-RNA protein 8, which has a role in RNA processing. Heterozygous PRPF8 variants have been associated with retinitis pigmentosa and neurodevelopmental disorders but not with phosphate metabolism. The patient underwent growth hormone (GH) stimulation tests which confirmed GH deficiency. Head MRI indicated partially empty sella. GH treatment was started at 15 years. Surprisingly, phosphate metabolism normalized during GH treatment, suggesting that hypophosphatemia was at least partly secondary to GH deficiency.
CONCLUSIONS: The evaluation of an adolescent with profound long-term hypophosphatemia revealed a pituitary developmental defect associated with a stop-gain variant in PRPF8. Hypophosphatemia alleviated with GH treatment. The pathological PRPF8 variant may contribute to abnormal pituitary development; however, its role in phosphate metabolism remains uncertain.