P052: Mitochondrial abnormalities in a patient with ReNU syndrome

episodes of lethargy associated with intercurrent illnesses and protein intake.Additional, poorly understood complications include pulmonary, renal, and inflammatory disorders.Here we describe a female with LPI diagnosed at age 11 years, in whom Trio Genome Sequencing identified biallelic variants of uncertain significance (VUS) in SLC7A7.Biochemical testing in plasma and urine helped to confirm the diagnosis.Treatment was initiated with improvement in the biochemical profile.Case Presentation: At diagnosis, key clinical findings included a history of at least three episodes of lethargy, two of which led to hospital admission in early childhood, as well as growth delay (height A, p.W121R) in trans in SLC7A7.Neither variant had previously been described in ClinVar.Follow-up biochemical testing showed normal plasma ammonia, and markedly elevated plasma glutamine and alanine with low lysine, arginine and ornithine.Urine amino acids showed elevated excretion of lysine approximately 2.5-fold the upper-limit of normal with normal excretion of all other amino acids, including arginine and ornithine.Urine orotic acid was normal.Treatment and Management: Initial treatment included low protein diet (1g/kg/day), citrulline supplementation (50-100mg/kg/day).After initial follow up, an oral nitrogen scavenger will be added.Outcome and Follow-Up: The patient was recently seen in clinic for the first follow-up appointment after approximately 5 weeks of therapy.She showed improvement in weight gain and biochemical profile (decreased plasma glutamine, normalization of alanine, still low but improved lysine and ornithine).Discussion: LPI is a rare and complex inborn error of metabolism with poorly understood multisystem involvement.Review of ten years of urine amino acid data from our laboratory identified only twelve urine amino acids profiles that were from individuals with LPI and only one of these, this patient, was a diagnostic sample.Interestingly, of all the urinary lysine concentrations, this case had the lowest value measuring ~2.5 fold above the normal reference range with normal concentrations of arginine and ornithine.This is not the typical pattern described in the literature.Conclusion: This case highlights the clinical utility of biochemical testing to support pathogenicity of two newly identified VUS, c.796_813dup, p.S266_T271dup and c.361T>A, p.W121R.Biochemical confirmation allowed prompt initiation of treatment.Comparison of urine amino acids from confirmed LPI patients demonstrates the variability of the pattern that can be observed at diagnosis and suggests careful attention should be given to amino acid profiles showing only elevated lysine.The medical management and clinical outcome of this patient have dramatically changed in view of this diagnosis.