一过性严重低磷血症伴青春期延迟和生长发育迟缓的新PRPF8致病变体。

IF 2.6 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM
Laura Koljonen, Pia Salonen, Salla Rusanen, Mervi K Mäyränpää, Minna Pekkinen, Outi Mäkitie
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引用次数: 0

摘要

简介儿童低磷血症是一种罕见疾病,可能由吸收不良、恶性肿瘤或遗传因素引起。长期低磷血症会导致发育障碍和佝偻病的影像学表现:我们对一名反复出现血浆磷酸盐浓度过低(低于 0.60 mmol/L)和发育不良的青少年男孩进行了详细的临床和遗传评估:结果:14 岁时,患者出现生长减速和青春期延迟。生化检查显示,尿磷酸盐丢失增加导致低磷血症;肾功能和维生素 D 状态正常。X光片显示有轻微的骨骺变化。已知的遗传性低磷血症基因检测呈阴性。通过三重外显子组分析和桑格测序,在 PRPF8 基因的保守 RNase H 同源结构域中发现了一个致病性杂合从新停止增益变异,c.5548C>T p.(Arg1850*).PRPF8 编码前 RNA 蛋白 8,在 RNA 处理中发挥作用。杂合子 PRPF8 变异与视网膜色素变性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,结果证实其缺乏生长激素。头部核磁共振成像(MRI)显示蝶鞍部分空虚。15 岁时开始接受 GH 治疗。令人惊讶的是,磷酸盐代谢在 GH 治疗期间恢复正常,这表明低磷血症至少部分是继发于生长激素缺乏症:总之,通过对一名患有长期严重低磷血症的青少年进行评估,发现其垂体发育缺陷与 PRPF8 停止增益变异有关。经 GH 治疗后,低磷血症有所缓解。病理 PRPF8 变异可能会导致垂体发育异常,但它在磷酸盐代谢中的作用仍不确定。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A de novo PRPF8 Pathogenic Variant in Transient Severe Hypophosphatemia with Delayed Puberty and Growth Failure.

Introduction: 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.

Conclusion: 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.

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来源期刊
Hormone Research in Paediatrics
Hormone Research in Paediatrics ENDOCRINOLOGY & METABOLISM-PEDIATRICS
CiteScore
4.90
自引率
6.20%
发文量
88
审稿时长
4-8 weeks
期刊介绍: The mission of ''Hormone Research in Paediatrics'' is to improve the care of children with endocrine disorders by promoting basic and clinical knowledge. The journal facilitates the dissemination of information through original papers, mini reviews, clinical guidelines and papers on novel insights from clinical practice. Periodic editorials from outstanding paediatric endocrinologists address the main published novelties by critically reviewing the major strengths and weaknesses of the studies.
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