From metabolic disorder to autoimmunity: lupus-like immune dysregulation in children with SLC7A7-associated lysinuric protein intolerance.

OBJECTIVE

To characterize the clinical and immunological features of lupus-like immune dysregulation in children with lysinuric protein intolerance (LPI) through case analysis and literature review.

METHODS

This study retrospectively analyzed the clinical records, genetic testing results, and immunological data of two LPI cases treated at Beijing Children's Hospital. A literature review was simultaneously performed to contextualize our findings.

RESULTS

The proband (Patient 1), a 1.5-year-old girl with homozygous SLC7A7 (c.625 + 1G > A) mutation, presented with growth retardation and multisystem involvement (hematologic, digestive, respiratory). Laboratory tests showed ANA positivity and hypocomplementemia. While initial therapy with glucocorticoids, immunosuppressants and dietary protein restriction showed benefit, treatment non-adherence resulted in disease progression culminating in fatal respiratory failure. Patient 2 (the proband's sister), carrying the same mutation, exhibited milder manifestations including growth retardation, interstitial lung disease, ANA positivity, hypocomplementemia, and proteinuria. With treatment, her condition stabilized, showing partial resolution of lung lesions and improved growth. Combining our two cases with 18 previously reported cases (total n = 20), common features included growth retardation (88.9%), renal involvement (72.2%), respiratory disease, and hematologic abnormalities. Rheumatologic markers included ANA positivity (90%), hypocomplementemia (85%), and anti-dsDNA antibodies (45%). Treatment primarily involved glucocorticoids and immunosuppressants, whereas plasma exchange and hematopoietic stem cell transplantation were used only rarely.

CONCLUSION

LPI-associated lupus-like immune dysregulation is rare and clinically heterogeneous. Accurate diagnosis requires an integrated assessment of genetic, metabolic, and immunologic data. Immunomodulatory therapy may be effective, but vigilance is essential due to infection risk and disease flares. Early recognition, management, and long-term follow-up are critical to improving prognosis.