Štajer Katarina, Kovač Neja, Šikonja Jaka, Mlinarič Matej, Bertok Sara, Brecelj Jernej, Debeljak Maruša, Kovač Jernej, Markelj Gašper, Neubauer David, Rus Rina, Žerjav Tanšek Mojca, Drole Torkar Ana, Zver Aleksandra, Battelino Tadej, Jiménez Torres Rosa, Grošelj Urh
Department of Endocrinology, Diabetes, and Metabolic Diseases, University Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia.
Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
Mol Genet Metab Rep. 2023 Jun 19;36:100986. doi: 10.1016/j.ymgmr.2023.100986. eCollection 2023 Sep.
Phosphoribosylpyrophosphate synthetase 1 (PRS-I) is an enzyme involved in nucleotide metabolism. Pathogenic variants in the are rare and PRS-I deficiency can manifest as three clinical syndromes: X-linked non-syndromic sensorineural deafness (DFN2), X-linked Charcot-Marie-Tooth neuropathy type 5 (CMTX5) and Arts syndrome. We present a Slovenian patient with PRS-I enzyme deficiency due to a novel pathogenic variant - c.424G > A (p.Val142Ile) in the gene, who presented with gross motor impairment, severe sensorineural deafness, balance issues, ataxia, and frequent respiratory infections. In addition, we report the findings of a systemic literature review of all described male cases of Arts syndrome and CMTX5 as well as intermediate phenotypes. As already proposed by other authors, our results confirm PRS-I deficiency should be viewed as a phenotypic continuum rather than three separate syndromes because there are multiple reports of patients with an intermediary clinical presentation.
磷酸核糖焦磷酸合成酶1（PRS-I）是一种参与核苷酸代谢的酶。该基因的致病变异罕见，PRS-I缺乏症可表现为三种临床综合征：X连锁非综合征性感音神经性耳聋（DFN2）、X连锁5型夏科-马里-图斯神经病变（CMTX5）和阿茨综合征。我们报告了一名斯洛文尼亚患者，由于该基因出现一种新的致病变异——c.424G>A（p.Val142Ile），导致PRS-I酶缺乏，表现为严重运动功能障碍、重度感音神经性耳聋、平衡问题、共济失调和频繁的呼吸道感染。此外，我们报告了对所有已描述的阿茨综合征和CMTX5男性病例以及中间表型进行系统文献综述的结果。正如其他作者已经提出的那样，我们的结果证实，PRS-I缺乏症应被视为一种表型连续体，而不是三种独立的综合征，因为有多项报告称患者临床表现为中间型。
