Abstract:

Objective: To summarize and review the clinical data of two children with lysinuric protein intolerance so as to improve its knowledge. Methods: Clinical data of two cases with lysinuric protein intolerance were summarized, including clinical manifestations, laboratory findings, renal pathological changes and family investigation. This study used next generation sequencing to screen all exons of genome in proband and her parents. Significant variants detected by next generation sequencing were confirmed by conventional Sanger sequencing and segregation analysis was performed using parental DNA and her brother samples.Results: The proband, a 10-year-old girl, presented with recurrent vomiting and episodes of diarrhea, aversion to protein-rich food and failure to thrive after weaning. She often had nasal hemorrhage since the age of 5 years. Peripheral blood cell count suggested white blood cell, red blood cell and platelet count were all under normal value. She had mild proteinuria and persistent microscopic hematuria at the age of 9.7 years. At the same time, laboratory tests showed that serum ferritin, lactate dehydrogenase and ammonia increased, and orotic acid increased in urine, but lysine, arginine and citrulline were not changed significantly in serum and urine. The pathology of renal biopsy suggested lupus nephritis. The proband's younger brother, 6.5-year-old, presented with recurrent vomiting, aversion to protein-rich food and failure to thrive after weaning. He had no episodes of diarrhea. laboratory tests also showed that serum ferritin, lactate dehydrogenase and ammonia increased, and orotic acid increased in urine, but lysine, arginine and citrulline were not changed significantly in serum and urine. Whole exon sequencing was performed in core family, including proband and her parents. Homozygous c.625+1G>A mutation in SLC7A7 gene was detected in proband, which was from her parents. The mutation was confirmed by Sanger sequencing in core family. The same mutation was found in proband's younger brother by Sanger sequencing. The proband was diagnosed as LPI complicted with SLE. The proband's younger brother was diagnosed as LPI.Conclusion: Due to the heterogeneity of LPI and lack of understanding of LPI for clinicians, it is easy to cause misdiagnosis or miss diagnosis. The SLC7A7 gene sequencing is the basis for diagnosis. LPI patients with systemic lupus erythematosus (SLE) is very rare. LPI patients complicated with SLE need glucocorticoid or immunosuppressive therapy. Mutations in SLC7A7 gene can cause SLE. whether SLC7A7 is one of the genes causing a single gene type SLE needs further study.

Key words: Lysine, Lysinuric protein intolerance, SLC7A7 gene, Systemic lupus erythematosus