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]

• Poor Growth

  The affected child was an 11-year old girl, who was diagnosed with LPI at 2-years of age, following early signs of protein intolerance, including vomiting, diarrhea, selective aversion, and poor growth. [cags.org.ae]

  Despite compliance with treatment, our patient’s growth remained poor (height −4.0 SDS) and the IGF-I remained low. She was therefore commenced on recombinant IGF-1 therapy at 9.9 years of age. [bone-abstracts.org]

  Lysine deficiency may cause many of the features of the disease that are not corrected by prevention of hyperammonemia, including enlargement of the liver and spleen, poor growth and delayed bone age, and osteoporosis. [ommbid.mhmedical.com]

  Growth, growth hormone deficiency. Growth retardation is commonly observed in children with LPI and is usually related to protein malnutrition. [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]

  With the lack of a clear genotype-phenotype relationship, the identification of mutations in patients may permit confirmation of the diagnosis but is not useful in predicting the severity of the clinical course [ 16 ]. [ojrd.biomedcentral.com]

• Failure to Thrive

  Failure to thrive, hepatosplenomegaly, hematological abnormalities, and hyperammonemic crisis are major clinical features. However, there has been no reported Korean patient with LPI as of yet. [ncbi.nlm.nih.gov]

  Clinical findings in LPI patients include: vomiting, diarrhea, failure to thrive, hepatosplenomegaly, bone marrow abnormalities, osteoporosis, episodes of coma, mental retardation, altered immune response, chronic renal disease and lung involvement, mainly [humpath.com]

• Nausea

  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]

  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]

  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]

• Asterixis

  […] cirrhosis anemia thrombocytopenia osteoporosis protein malnutrition protein intolerance failure to thrive retarded physical development diarrhea malabsorption hepatomegaly (enlarged liver) vomiting liver cirrhosis mental retardation attacks of stupor and asterixis [humpath.com]

• Cyanosis

  Diminished breath sounds, inspiratory crackles, subcostal and suprasternal retractions, cyanosis, and, more rarely, digital clubbing can be found on physical examination. Diffuse reticulonodular densities are common on radiologic evaluation. [ncbi.nlm.nih.gov]

• 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]

• Delayed Bone Age

  The patients show failure to thrive, poor appetite, growth retardation, enlarged liver and spleen, prominent osteoporosis and osteopenia, delayed bone age and spontaneous protein aversion. Forced feeding of protein may lead to convulsions and coma. [en.wikipedia.org]

  The patients show failure to thrive, poor appetite, growth retardation, enlarged liver and spleen, prominent osteoporosis, delayed bone age and spontaneous protein aversion. Forced feeding of protein may lead to convulsions and coma. [wikidoc.org]

  Osteoporosis is prominent, and fractures are not uncommon; bone age is delayed. The mental prognosis varies from normal development to moderate retardation; most patients are normal. Four patients have had psychotic periods. [ommbid.mhmedical.com]

• Bilirubin Increased

  On starting feeds on day 10 of hospitalization, her bilirubin increased to 24.2 mg/dl (direct = 11.5 mg/dl), SGOT to 160 IU/L, SGPT to 66 IU/L, and serum ammonia increased to 160. [mjdrdypu.org]

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]

Citrulline has also been found effective as a treatment option in LPI as it is changed to arginine in our body. [mjdrdypu.org]

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]

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]

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

Etiology In LPI, urinary excretion of cationic amino acids ( ornithine, arginine and lysine ) is increased and these amino acids are poorly absorbed from the intestine. [wikidoc.org]

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]