Lysinuric protein intolerance (LPI) is an inborn error of metabolism which usually presents in infancy with failure to thrive and vomiting. Two patients are described who presented in adult life with hyperammonaemic coma due to LPI. [ncbi.nlm.nih.gov]

• Unconsciousness

  They were of normal intellect and had maintained good health, until presentation in their thirties, by unconscious dietary protein avoidance. [ncbi.nlm.nih.gov]

• Severe Clinical Course

  However, the severe clinical course of this disorder suggests that LPI should be regarded as a severe multisystem disease with uncertain outcome. [ncbi.nlm.nih.gov]

  Lysinuric protein intolerance characterized by bone marrow abnormalities and severe clinical course. J. Pediatr. 126, 246–251 (1995). 5 Palacin, M., Estevez, R., Bertran, J. & Zorzano, A. [doi.org]

  Lysinuric protein intolerance characterized by bone marrow abnormalities and severe clinical course. J Pediatr. 1995;126:246–51. View Article PubMed Google Scholar Esposito V, Lettiero T, Fecarotta S, Sebastio G, Parenti G, Salerno M. [ojrd.biomedcentral.com]

• Failure to Thrive

  Failure to thrive and signs of haemophagocytic-lymphohistiocytosis were almost constant. Recurrent acute pancreatitis occurred in 2 patients. Ten patients developed an early lung disease. [ncbi.nlm.nih.gov]

• Nausea

  Two patients had mild nausea but no hyperammonemia and one patient had moderate hyperammonemia (peak, 112 micromol/L) at the end of the infusion. [ncbi.nlm.nih.gov]

  Because the body cannot effectively break down these amino acids, which are found in many protein-rich foods, nausea and vomiting are typically experienced after ingesting protein. [ghr.nlm.nih.gov]

  The patients have periods of nausea and vomiting, and they develop an aversion to protein-rich food, fail to thrive, have hepato- and splenomegaly and osteoporosis, and their growth becomes stunted. [link.springer.com]

  Because the body cannot effectively break down these amino acids, which are found in many protein-rich foods, individuals experience nausea and vomiting after ingesting protein. [rarediseases.info.nih.gov]

  Consequently, nausea and vomiting occur, and aversion to protein-rich food develops. The patients fail to thrive, and symptoms of protein malnutrition are further aggravated by lysine deficiency. [ommbid.mhmedical.com]

• Retinal Pigmentation

  RNA in situ hybridization data on mouse embryos confirm the expression in kidney and intestine and, interestingly, reveal that SLC7A8 is also highly expressed in eye, in retinal pigmented epithelium, and in tooth buds at day 16.5 of gestation. [ncbi.nlm.nih.gov]

• Cognitive Disorder

  More than half of the patients presented with cognitive disorders. Though this complication has not been reported in the literature, it can be easily explained by chronic hyperammonemia. [ojrd.biomedcentral.com]

• Ischemic Changes

  Positron emission tomography of the heart and a treadmill test revealed ischemic changes in the patient, which were improved by the L-arginine infusion. [ncbi.nlm.nih.gov]

Management and treatment Treatment revolves around protein-restricted diet and supplement of lysine, ornithine, and citrulline. The complication of pulmonary alveolar proteinosis has been reported to be successfully treated by whole lung lavage. [orpha.net]

Treatment of Acute Hyperammonemic Crises Pharmacologic management. [ncbi.nlm.nih.gov]

Prognosis Prognosis varies depending on pulmonary complications.Pulmonary involvement represents a major cause of impaired clinical course and fatal outcome. The documents contained in this web site are presented for information purposes only. [orpha.net]

The importance of early diagnosis for better prognosis of LPI is emphasized. 2016 Japan Pediatric Society. [ncbi.nlm.nih.gov]

Treatment and prognosis Treatment of LPI consists of protein-restricted diet and supplementation with oral citrulline. [wikidoc.org]

Pulmonary involvement appears to play a major role in the prognosis of the disease. [ojrd.biomedcentral.com]

[…] renal complications, and treatment of such complications with corticosteroids is found to be effective in some patients. [1] Therapy with bisphosphonates is currently under investigation as osteopenia leading to osteoporosis is a major feature. [5] The prognosis [mjdrdypu.org]

Possible etiologic factors responsible for hemophagocytosis and the differential diagnosis of hemophagic syndromes are discussed. [ncbi.nlm.nih.gov]

Etiology It is caused by defective cationic amino acid transport at the basolateral membrane of epithelial cells in the kidney and intestine. LPI is caused by mutations of solute carrier family 7A member 7 ( SLC7A7 ) located at chromosome 14q11.2. [orpha.net]

Summary Epidemiology It is mainly found in Italy and Finland where prevalence is 1/60,000. [orpha.net]

METHODS: An epidemiological nationwide survey of LPI patients was carried out via mail to all domestic university and general hospitals in Japan. [ncbi.nlm.nih.gov]

Nephrotoxins 1275 Urinary Tract Infections 1299 Vesicoureteral Reflux and Renal Scarring 1311 Obstructive Uropathy 1337 Bladder Dysfunction in Children 1379 Urolithiasis 1405 Pediatric Renal Tumors 1431 Epidemiology of Hypertension 1459 Pathophysiology [books.google.com]

Specifically, immune dysfunction potentially attributable to nitric oxide (NO) overproduction secondary to arginine intracellular trapping (due to defective efflux from the cell) might be a crucial pathophysiological route explaining many of LPI complications [ncbi.nlm.nih.gov]

Nephrotoxins 1275 Urinary Tract Infections 1299 Vesicoureteral Reflux and Renal Scarring 1311 Obstructive Uropathy 1337 Bladder Dysfunction in Children 1379 Urolithiasis 1405 Pediatric Renal Tumors 1431 Epidemiology of Hypertension 1459 Pathophysiology [books.google.com]

Lysinuric protein intolerance: mechanisms of pathophysiology. Mol Genet Metab. 2004 Apr;81 Suppl 1:S27-37. Review. Sperandeo MP, Andria G, Sebastio G. Lysinuric protein intolerance: update and extended mutation analysis of the SLC7A7 gene. [ghr.nlm.nih.gov]

In the older sibling, the hyperammonemia induced by the intravenous amino nitrogen load was completely prevented by the oral supplement of citrulline, but not completely prevented in the younger sibling. [ncbi.nlm.nih.gov]