We describe two sporadic and two familial cases with loss-of-function variants in PRPS1, which is located on the X chromosome and encodes phosphoribosyl pyrophosphate synthetase 1 (PRS-1). We illustrate the clinical variability associated with decreased PRS-1 activity, ranging from mild isolated hearing loss to severe encephalopathy. One of the variants we identified has already been reported with a phenotype similar to our patient's, whereas the other three were unknown. The clinical and biochemical information we provide will hopefully contribute to gain insight into the correlation between genotype and phenotype of this rare condition, both in females and in males. Moreover, our observation of a new family in which hemizygous males display hearing loss without any neurological or ophthalmological symptoms prompts us to suggest analysing PRPS1 in cases of isolated hearing loss. Eventually, PRPS1 variants should be considered as a differential diagnosis of mitochondrial disorders.

我们描述了PRPS1中两例散发性和两例家族性功能丧失的病例，它位于X染色体上，编码磷酸核糖焦磷酸合成酶1（PRS-1）。我们举例说明了与PRS-1活性降低相关的临床变异性，范围从轻度孤立性听力损失到严重脑病。我们鉴定出的一种变体已被报道具有与患者相似的表型，而其他三种则未知。我们提供的临床和生化信息有望有助于深入了解这种罕见病的基因型和表型之间的相关性，无论是女性还是男性。而且，我们对半合子男性显示听力下降而没有任何神经或眼科症状的新家庭的观察促使我们建议在孤立性听力下降的情况下分析PRPS1。最终，PRPS1变异体应被视为线粒体疾病的鉴别诊断。