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Background <p>Monogenic lupus is a rare but severe form of systemic lupus erythematosus (SLE) that typically manifests during childhood. Mutations in <i>SLC7A7</i> cause lysinuric protein intolerance (LPI), and this gene has been implicated in monogenic lupus. This study aimed to investigate the clinical features, treatment strategies, and outcomes of pediatric patients with monogenic lupus caused by <i>SLC7A7</i> mutations.</p> Methods <p>We conducted a retrospective single-center study of pediatric patients with SLE who fulfilled the 2012 SLICC and/or 2019 EULAR/ACR classification criteria and underwent next-generation sequencing because of early onset or atypical clinical features. Patients carrying biallelic pathogenic or likely pathogenic variants in <i>SLC7A7</i> together with biochemical evidence of LPI were classified as having <i>SLC7A7</i>-associated monogenic lupus. Their clinical and immunological characteristics, treatment strategies, and outcomes were compared with those of SLE patients without identifiable monogenic variants.</p> Results <p>Among pediatric SLE patients who underwent next-generation sequencing for suspected monogenic etiology, six were identified with biallelic <i>SLC7A7</i> variants and biochemical evidence of lysinuric protein intolerance, accounting for 31.6% of all monogenic lupus cases in this cohort. The mean age at SLE diagnosis in the <i>SLC7A7</i>-associated monogenic lupus group was 6.6 years, and patients were followed for an average of 5.5 years. In the overall LPI cohort (<i>n</i> = 12), the median age of symptom onset was 1 year and the mean age at LPI diagnosis was 7.7 years. The recurrent splice-site mutation c.625 + 1G &gt; A was the most frequent variant, detected in 14 of 24 alleles. Compared with gene-negative SLE patients, those with <i>SLC7A7</i>-associated monogenic lupus more frequently exhibited protein intolerance, osteopenia, short stature, and hyperferritinemia (all <i>p</i> &lt; 0.05). Treatment consisted of combined immunosuppressive and metabolic therapies, and at the last follow-up 83.3% (5/6) of patients had achieved and maintained a Lupus Low Disease Activity State (LLDAS).</p> Conclusions <p>In Chinese patients with lysinuric protein intolerance, this study suggests an association with an increased susceptibility to developing SLE. Given the small LPI-SLE subgroup, these findings require validation in larger cohorts. Within this cohort, the splice-site mutation c.625 + 1G &gt; A was the most frequently observed <i>SLC7A7</i> variant. Furthermore, in children diagnosed with SLE, the presentation of a metabolic triad—protein intolerance, short stature, and osteopenia—should raise suspicion for <i>SLC7A7</i>-associated monogenic lupus and prompt genetic and metabolic evaluation, which could facilitate early diagnosis and timely intervention.</p>

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Monogenic lupus with SLC7A7 mutations: a retrospective study from a Chinese center

  • 期刊论文

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  • 发表日期：

    2026年3月13日

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  • Yifan Li,
  • Qianying Lv,
  • Wei Lu,
  • Haimei Liu,
  • Jiayan Feng,
  • Wanzhen Guan,
  • Yinv Gong,
  • Qiaoqian Zeng,
  • Xiaomei Zhang,
  • Hong Xu,
  • Li Sun

摘要

Background

Monogenic lupus is a rare but severe form of systemic lupus erythematosus (SLE) that typically manifests during childhood. Mutations in SLC7A7 cause lysinuric protein intolerance (LPI), and this gene has been implicated in monogenic lupus. This study aimed to investigate the clinical features, treatment strategies, and outcomes of pediatric patients with monogenic lupus caused by SLC7A7 mutations.

Methods

We conducted a retrospective single-center study of pediatric patients with SLE who fulfilled the 2012 SLICC and/or 2019 EULAR/ACR classification criteria and underwent next-generation sequencing because of early onset or atypical clinical features. Patients carrying biallelic pathogenic or likely pathogenic variants in SLC7A7 together with biochemical evidence of LPI were classified as having SLC7A7-associated monogenic lupus. Their clinical and immunological characteristics, treatment strategies, and outcomes were compared with those of SLE patients without identifiable monogenic variants.

Results

Among pediatric SLE patients who underwent next-generation sequencing for suspected monogenic etiology, six were identified with biallelic SLC7A7 variants and biochemical evidence of lysinuric protein intolerance, accounting for 31.6% of all monogenic lupus cases in this cohort. The mean age at SLE diagnosis in the SLC7A7-associated monogenic lupus group was 6.6 years, and patients were followed for an average of 5.5 years. In the overall LPI cohort (n = 12), the median age of symptom onset was 1 year and the mean age at LPI diagnosis was 7.7 years. The recurrent splice-site mutation c.625 + 1G > A was the most frequent variant, detected in 14 of 24 alleles. Compared with gene-negative SLE patients, those with SLC7A7-associated monogenic lupus more frequently exhibited protein intolerance, osteopenia, short stature, and hyperferritinemia (all p < 0.05). Treatment consisted of combined immunosuppressive and metabolic therapies, and at the last follow-up 83.3% (5/6) of patients had achieved and maintained a Lupus Low Disease Activity State (LLDAS).

Conclusions

In Chinese patients with lysinuric protein intolerance, this study suggests an association with an increased susceptibility to developing SLE. Given the small LPI-SLE subgroup, these findings require validation in larger cohorts. Within this cohort, the splice-site mutation c.625 + 1G > A was the most frequently observed SLC7A7 variant. Furthermore, in children diagnosed with SLE, the presentation of a metabolic triad—protein intolerance, short stature, and osteopenia—should raise suspicion for SLC7A7-associated monogenic lupus and prompt genetic and metabolic evaluation, which could facilitate early diagnosis and timely intervention.