Lysinuric protein intolerance: Pearls to detect this otherwise easily missed diagnosis

Abstract

BACKGROUND: Lysinuric protein intolerance (LPI) is a rare autosomal recessive disorder characterized by deficient membrane transport of cationic amino acids. It is caused by pathogenic variants in SLC7A7, resulting in impairment of intestinal import and renal proximal tubule loss of the affected amino acids. LPI typically presents with gastrointestinal symptoms, such as vomiting, diarrhea, and failure to thrive. CASE REPORT: A 4-year-old African-American boy presented with multiple respiratory tract infections, weight loss in the setting of chronic diarrhea and worsening abdominal distention, and multiple episodes of rectal prolapse. Development was unaffected. Laboratory examination demonstrated mild anemia, hypokalemia and hypoalbuminemia, transaminitis, and normal ammonia. Initial urine amino acid analysis did not show major elevations of lysine and ornithine, often lower than expected in the setting of malnutrition. Upon initiation of total parenteral nutrition (TPN), his urine amino acids showed a characteristic profile of dibasic aminoaciduria. CONCLUSIONS: Failure to thrive, chronic diarrhea, and hepatomegaly should raise suspicion for LPI. Urine amino acids can be normal in this condition in the setting of malnutrition, a common complication of the disease. Additionally, it has been previously shown that the plasma arginine and ornithine concentration is higher in LPI subjects.

A complication of lysinuric protein intolerance: Intermittent haemophagocytic lymphohistiocytosis

“…Patients who achieve metabolic control by complying with diet and supportive treatments may experience fewer attacks. 5,6 Unfortunately, it took time to achieve metabolic control and decrease the frequency of attacks in our patients.…”

“…4 It is inherited by pathological variants of the SLC7A7 gene located on the 14q11.2 locus of chromosome 14. 5,6 LPI been considered as a benign urea cycle disease for a long while and suggested receiving adequate treatment with an appropriate low-protein diet and L-citrulline replacement. On the contrary, in the light of our current knowledge, it is an entity with high morbidity and mortality with multi-organ involvement.…”

“…LPI is an autosomal recessively inherited disorder of dibasic amino acid metabolism 4 . It is inherited by pathological variants of the SLC7A7 gene located on the 14q11.2 locus of chromosome 14 5,6 . LPI has been considered as a benign urea cycle disease for a long while and suggested receiving adequate treatment with an appropriate low‐protein diet and L‐citrulline replacement.…”

DefectiveSlc7a7transport reduces erythropoietin compromising erythropoiesis and iron homeostasis

“…CC-BY 4.0 International license made available under a (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is The copyright holder for this preprint this version posted August 16, 2021. ; https://doi.org/10.1101/2021.08.15.456393 doi: bioRxiv preprint 5 mutations in Slc7a7 gene have abnormal blood count, as well as microcytic anemia (Alqarajeh et al, 2020;Rajantie et al, 1980). To date, the standard treatment for LPI mainly consists on a low-protein based diet supplemented with oral citrulline (Lukkarinen et al, 2003), where citrulline is intracellularly converted to arginine in renal epithelial cells.…”

“…Consequently leading to reduced body weight, brain edema and pulmonary alveolar proteinosis between other complications (Bodoy et al, 2019). In addition, several studies found that patients with one or several mutations in Slc7a7 gene have abnormal blood count, as well as microcytic anemia (Alqarajeh et al, 2020; Rajantie et al, 1980). To date, the standard treatment for LPI mainly consists on a low-protein based diet supplemented with oral citrulline (Lukkarinen et al, 2003), where citrulline is intracellularly converted to arginine in renal epithelial cells.…”