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Olli Simell - One of the best experts on this subject based on the ideXlab platform.
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Transport Defects of Amino Acids at the Cell Membrane: Cystinuria, Hartnup Disease, and Lysinuric Protein Intolerance
Inborn Metabolic Diseases, 2020Co-Authors: Olli Simell, K Parto, K. Näntö-salonenAbstract:Inherited defects in amino acid transport at the cell membrane are usually expressed as selective renal aminoaciduria, i.e., the concentration of affected amino acids is high in the urine, but normal or low in plasma. Intestinal absorption of the affected amino acids is almost always impaired as well. The clinical symptoms may be due to substrate excess in the urine or deficiency of the substrates in the body. Consequently, the symptoms in cystinuria are caused by formation of renal stones, as cystine is poorly soluble in urine; the pellagra-like skin disease and ataxia in Hartnup disease are due to deficiency of tryptophan and, subsequently, of niacin; and hyperammonemia in Lysinuric Protein Intolerance is the result of deficiency of arginine and ornithine, which are obligatory urea cycle intermediates.
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exploring the transcriptomic variation caused by the finnish founder mutation of Lysinuric Protein Intolerance lpi
Molecular Genetics and Metabolism, 2012Co-Authors: Maaria Tringham, Laura Tanner, Kirsti Nantosalonen, Harri Niinikoski, Johanna Kurko, Johannes Tuikkala, Olli Nevalainen, Marja Hietala, Olli SimellAbstract:Abstract Lysinuric Protein Intolerance (LPI) is an autosomal recessive disorder caused by mutations in cationic amino acid transporter gene SLC7A7 . Although all Finnish patients share the same homozygous mutation, their clinical manifestations vary greatly. The symptoms range from failure to thrive, Protein aversion, anemia and hyperammonaemia, to immunological abnormalities, nephropathy and pulmonary alveolar Proteinosis. To unravel the molecular mechanisms behind those symptoms not explained directly by the primary mutation, gene expression profiles of LPI patients were studied using genome-wide microarray technology. As a result, we discovered 926 differentially-expressed genes, including cationic and neutral amino acid transporters. The functional annotation analysis revealed a significant accumulation of such biological processes as inflammatory response, immune system processes and apoptosis. We conclude that changes in the expression of genes other than SLC7A7 may be linked to the various symptoms of LPI, indicating a complex interplay between amino acid transporters and various cellular processes.
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growth hormone therapy is safe and effective in patients with Lysinuric Protein Intolerance
JIMD reports, 2011Co-Authors: Harri Niinikoski, Olli Simell, Laura Tanner, Risto Lapatto, Matti Nuutinen, Kirsti NantosalonenAbstract:Background: Lysinuric Protein Intolerance (LPI) is an autosomal recessive cationic amino acid transport defect characterized by episodes of postprandial hyperammonemias and spontaneous Protein aversion. Subnormal growth is common in spite of appropriate nutritional therapy. Growth hormone (GH) therapy promotes appetite, Protein synthesis and accretion, but its possible growth-promoting effects and safety in patients with LPI are poorly known.
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Combined hyperlipidemia in patients with Lysinuric Protein Intolerance.
Journal of inherited metabolic disease, 2010Co-Authors: Laura M Tanner, K. Näntö-salonen, Harri Niinikoski, Olli SimellAbstract:Lysinuric Protein Intolerance (LPI) is an autosomal recessive disorder characterized by defective transport of cationic amino acids lysine, arginine, and ornithine. Low plasma concentrations of arginine and ornithine lead to impaired urea cycle function and, subsequently, decreased Protein tolerance. Patients often develop natural aversion to Protein-rich foods, which may predispose them to nutritional problems. The objective of this retrospective study was to investigate lipid values and efficacy of lipid-lowering therapy in patients with LPI. Serum total and high-density-lipoProtein (HDL)-cholesterol and triglyceride concentrations were analyzed in 39 Finnish LPI patients (14 males) aged 3-64 years. Dietary intakes were analyzed from food records. Mean [standard deviation (SD)] serum and HDL-cholesterol and triglyceride concentrations were 7.16 (2.13) mmol/l, 1.21 (0.58) mmol/l, and 4.0 (2.4) mmol/l, respectively. Patients with renal dysfunction had marginally higher total cholesterol and significantly higher triglyceride concentration than patients without renal impairment. Twenty-two patients were started on 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (atorvastatin or simvastatin). After 6 months, serum cholesterol and triglyceride concentrations had decreased by 32% (p < 0.001), whereas HDL-cholesterol had increased by 13% (p = 0.016). Serum cholesterol and triglyceride values are markedly elevated in LPI patients. Although the mechanism of combined hyperlipidemia remains unknown and is not explained by fat consumption, hyperlipidemia is clearly progressive with age, suggesting that starting statin therapy early is probably beneficial. Statins are well-tolerated and efficacious in LPI.
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combined hyperlipidemia in patients with Lysinuric Protein Intolerance
Journal of Inherited Metabolic Disease, 2010Co-Authors: Kirsti Nantosalonen, Laura Tanner, Harri Niinikoski, Olli SimellAbstract:Background and aims Lysinuric Protein Intolerance (LPI) is an autosomal recessive disorder characterized by defective transport of cationic amino acids lysine, arginine, and ornithine. Low plasma concentrations of arginine and ornithine lead to impaired urea cycle function and, subsequently, decreased Protein tolerance. Patients often develop natural aversion to Protein-rich foods, which may predispose them to nutritional problems. The objective of this retrospective study was to investigate lipid values and efficacy of lipid-lowering therapy in patients with LPI.
Laura Tanner - One of the best experts on this subject based on the ideXlab platform.
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inhaled sargramostim induces resolution of pulmonary alveolar Proteinosis in Lysinuric Protein Intolerance
JIMD reports, 2016Co-Authors: Laura Tanner, Kirsti Nantosalonen, Harri Niinikoski, Juha Mykkanen, Johanna Kurko, Maaria Tringham, Heikki LukkarinenAbstract:Pulmonary alveolar Proteinosis (PAP) is a potentially fatal complication of Lysinuric Protein Intolerance (LPI), an inherited disorder of cationic amino acid transport. The patients often present with mild respiratory symptoms, which may rapidly progress to acute respiratory failure responding poorly to conventional treatment with steroids and bronchoalveolar lavations (BALs). The pathogenesis of PAP in LPI is still largely unclear. In previous studies, we have shown disturbances in the function and activity of alveolar macrophages of these patients, suggesting that increasing the activity and the number of macrophages by recombinant human GM-CSF (rhuGM-CSF) might be beneficial in this patient group.
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exploring the transcriptomic variation caused by the finnish founder mutation of Lysinuric Protein Intolerance lpi
Molecular Genetics and Metabolism, 2012Co-Authors: Maaria Tringham, Laura Tanner, Kirsti Nantosalonen, Harri Niinikoski, Johanna Kurko, Johannes Tuikkala, Olli Nevalainen, Marja Hietala, Olli SimellAbstract:Abstract Lysinuric Protein Intolerance (LPI) is an autosomal recessive disorder caused by mutations in cationic amino acid transporter gene SLC7A7 . Although all Finnish patients share the same homozygous mutation, their clinical manifestations vary greatly. The symptoms range from failure to thrive, Protein aversion, anemia and hyperammonaemia, to immunological abnormalities, nephropathy and pulmonary alveolar Proteinosis. To unravel the molecular mechanisms behind those symptoms not explained directly by the primary mutation, gene expression profiles of LPI patients were studied using genome-wide microarray technology. As a result, we discovered 926 differentially-expressed genes, including cationic and neutral amino acid transporters. The functional annotation analysis revealed a significant accumulation of such biological processes as inflammatory response, immune system processes and apoptosis. We conclude that changes in the expression of genes other than SLC7A7 may be linked to the various symptoms of LPI, indicating a complex interplay between amino acid transporters and various cellular processes.
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growth hormone therapy is safe and effective in patients with Lysinuric Protein Intolerance
JIMD reports, 2011Co-Authors: Harri Niinikoski, Olli Simell, Laura Tanner, Risto Lapatto, Matti Nuutinen, Kirsti NantosalonenAbstract:Background: Lysinuric Protein Intolerance (LPI) is an autosomal recessive cationic amino acid transport defect characterized by episodes of postprandial hyperammonemias and spontaneous Protein aversion. Subnormal growth is common in spite of appropriate nutritional therapy. Growth hormone (GH) therapy promotes appetite, Protein synthesis and accretion, but its possible growth-promoting effects and safety in patients with LPI are poorly known.
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combined hyperlipidemia in patients with Lysinuric Protein Intolerance
Journal of Inherited Metabolic Disease, 2010Co-Authors: Kirsti Nantosalonen, Laura Tanner, Harri Niinikoski, Olli SimellAbstract:Background and aims Lysinuric Protein Intolerance (LPI) is an autosomal recessive disorder characterized by defective transport of cationic amino acids lysine, arginine, and ornithine. Low plasma concentrations of arginine and ornithine lead to impaired urea cycle function and, subsequently, decreased Protein tolerance. Patients often develop natural aversion to Protein-rich foods, which may predispose them to nutritional problems. The objective of this retrospective study was to investigate lipid values and efficacy of lipid-lowering therapy in patients with LPI.
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carnitine deficiency and l carnitine supplementation in Lysinuric Protein Intolerance
Metabolism-clinical and Experimental, 2008Co-Authors: Laura Tanner, Kirsti Nantosalonen, Jaana Venetoklis, S Kotilainen, Harri Niinikoski, Kirsi Huoponen, Mohamed S Rashed, Maija Aalto, Olli SimellAbstract:Abstract The aim of the study was to investigate the prevalence and mechanisms of development of carnitine deficiency in patients with Lysinuric Protein Intolerance (LPI). In our cohort of 37 Finnish patients with LPI, 8 (8-52 years of age) have been diagnosed with hypocarnitinemia. Their free and total serum carnitine levels, acyl carnitine profiles, renal function, diet, and medication were compared with the data from 8 age- and sex-matched patients with LPI not treated with carnitine supplementation. In patients with LPI, hypocarnitinemia was strongly associated with female sex, renal insufficiency, and the use of ammonia-scavenging drugs. Of the 8 hypocarnitinemic patients, 3 complained of muscle weakness, and their symptoms disappeared during carnitine supplementation. Oral lysine supplementation did not correct hypocarnitinemia in our patients. The patients with LPI are at considerable risk for carnitine deficiency. Supplementation of hypocarnitinemic LPI patients with oral l -carnitine improved serum total carnitine values, but the ratio of free and total carnitine remained subnormal in all supplemented patients except one. Furthermore, decreased ratio of free and total serum carnitine was common even in LPI patients with normal total serum carnitine concentration.
Kirsti Nantosalonen - One of the best experts on this subject based on the ideXlab platform.
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inhaled sargramostim induces resolution of pulmonary alveolar Proteinosis in Lysinuric Protein Intolerance
JIMD reports, 2016Co-Authors: Laura Tanner, Kirsti Nantosalonen, Harri Niinikoski, Juha Mykkanen, Johanna Kurko, Maaria Tringham, Heikki LukkarinenAbstract:Pulmonary alveolar Proteinosis (PAP) is a potentially fatal complication of Lysinuric Protein Intolerance (LPI), an inherited disorder of cationic amino acid transport. The patients often present with mild respiratory symptoms, which may rapidly progress to acute respiratory failure responding poorly to conventional treatment with steroids and bronchoalveolar lavations (BALs). The pathogenesis of PAP in LPI is still largely unclear. In previous studies, we have shown disturbances in the function and activity of alveolar macrophages of these patients, suggesting that increasing the activity and the number of macrophages by recombinant human GM-CSF (rhuGM-CSF) might be beneficial in this patient group.
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exploring the transcriptomic variation caused by the finnish founder mutation of Lysinuric Protein Intolerance lpi
Molecular Genetics and Metabolism, 2012Co-Authors: Maaria Tringham, Laura Tanner, Kirsti Nantosalonen, Harri Niinikoski, Johanna Kurko, Johannes Tuikkala, Olli Nevalainen, Marja Hietala, Olli SimellAbstract:Abstract Lysinuric Protein Intolerance (LPI) is an autosomal recessive disorder caused by mutations in cationic amino acid transporter gene SLC7A7 . Although all Finnish patients share the same homozygous mutation, their clinical manifestations vary greatly. The symptoms range from failure to thrive, Protein aversion, anemia and hyperammonaemia, to immunological abnormalities, nephropathy and pulmonary alveolar Proteinosis. To unravel the molecular mechanisms behind those symptoms not explained directly by the primary mutation, gene expression profiles of LPI patients were studied using genome-wide microarray technology. As a result, we discovered 926 differentially-expressed genes, including cationic and neutral amino acid transporters. The functional annotation analysis revealed a significant accumulation of such biological processes as inflammatory response, immune system processes and apoptosis. We conclude that changes in the expression of genes other than SLC7A7 may be linked to the various symptoms of LPI, indicating a complex interplay between amino acid transporters and various cellular processes.
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growth hormone therapy is safe and effective in patients with Lysinuric Protein Intolerance
JIMD reports, 2011Co-Authors: Harri Niinikoski, Olli Simell, Laura Tanner, Risto Lapatto, Matti Nuutinen, Kirsti NantosalonenAbstract:Background: Lysinuric Protein Intolerance (LPI) is an autosomal recessive cationic amino acid transport defect characterized by episodes of postprandial hyperammonemias and spontaneous Protein aversion. Subnormal growth is common in spite of appropriate nutritional therapy. Growth hormone (GH) therapy promotes appetite, Protein synthesis and accretion, but its possible growth-promoting effects and safety in patients with LPI are poorly known.
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combined hyperlipidemia in patients with Lysinuric Protein Intolerance
Journal of Inherited Metabolic Disease, 2010Co-Authors: Kirsti Nantosalonen, Laura Tanner, Harri Niinikoski, Olli SimellAbstract:Background and aims Lysinuric Protein Intolerance (LPI) is an autosomal recessive disorder characterized by defective transport of cationic amino acids lysine, arginine, and ornithine. Low plasma concentrations of arginine and ornithine lead to impaired urea cycle function and, subsequently, decreased Protein tolerance. Patients often develop natural aversion to Protein-rich foods, which may predispose them to nutritional problems. The objective of this retrospective study was to investigate lipid values and efficacy of lipid-lowering therapy in patients with LPI.
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carnitine deficiency and l carnitine supplementation in Lysinuric Protein Intolerance
Metabolism-clinical and Experimental, 2008Co-Authors: Laura Tanner, Kirsti Nantosalonen, Jaana Venetoklis, S Kotilainen, Harri Niinikoski, Kirsi Huoponen, Mohamed S Rashed, Maija Aalto, Olli SimellAbstract:Abstract The aim of the study was to investigate the prevalence and mechanisms of development of carnitine deficiency in patients with Lysinuric Protein Intolerance (LPI). In our cohort of 37 Finnish patients with LPI, 8 (8-52 years of age) have been diagnosed with hypocarnitinemia. Their free and total serum carnitine levels, acyl carnitine profiles, renal function, diet, and medication were compared with the data from 8 age- and sex-matched patients with LPI not treated with carnitine supplementation. In patients with LPI, hypocarnitinemia was strongly associated with female sex, renal insufficiency, and the use of ammonia-scavenging drugs. Of the 8 hypocarnitinemic patients, 3 complained of muscle weakness, and their symptoms disappeared during carnitine supplementation. Oral lysine supplementation did not correct hypocarnitinemia in our patients. The patients with LPI are at considerable risk for carnitine deficiency. Supplementation of hypocarnitinemic LPI patients with oral l -carnitine improved serum total carnitine values, but the ratio of free and total carnitine remained subnormal in all supplemented patients except one. Furthermore, decreased ratio of free and total serum carnitine was common even in LPI patients with normal total serum carnitine concentration.
Pentti Aula - One of the best experts on this subject based on the ideXlab platform.
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characterization of the Lysinuric Protein Intolerance lpi region within t cell receptor α δ gene cluster on chromosome site 14qll
Hereditas, 2004Co-Authors: Tuija Lauteala, Olli Simell, Marja-liisa Savontaus, Juha Mykkanen, Nina Horellikuitunen, Johanna Aaltonen, Paulina Paavola, Pentti AulaAbstract:: Lysinuric Protein Intolerance is a recessively inherited metabolic disease characterized by defective efflux of cationic amino acids at the basolateral membrane of the intestinal and renal tubular epithelium. Linkage analysis and further linkage disequilibrium in Finnish LPI families have earlier assigned LPI gene locus within or in close vicinity of T-cell receptor alpha/delta gene cluster on chromosome site 14q11. In the present work we have characterized the linkage defined LPI region using RH-mapping and fiber-FISH and searched the LPI gene from the reported sequence of the T-cell receptor gene.
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Characterization of the Lysinuric Protein Intolerance (LPI) Region within T‐cell Receptor α/δ Gene Cluster on Chromosome Site 14qll
Hereditas, 2004Co-Authors: Tuija Lauteala, Olli Simell, Marja-liisa Savontaus, Juha Mykkanen, Johanna Aaltonen, Paulina Paavola, Nina Horelli-kuitunen, Pentti AulaAbstract:: Lysinuric Protein Intolerance is a recessively inherited metabolic disease characterized by defective efflux of cationic amino acids at the basolateral membrane of the intestinal and renal tubular epithelium. Linkage analysis and further linkage disequilibrium in Finnish LPI families have earlier assigned LPI gene locus within or in close vicinity of T-cell receptor alpha/delta gene cluster on chromosome site 14q11. In the present work we have characterized the linkage defined LPI region using RH-mapping and fiber-FISH and searched the LPI gene from the reported sequence of the T-cell receptor gene.
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genetic homogeneity of Lysinuric Protein Intolerance
European Journal of Human Genetics, 1998Co-Authors: Tuija Lauteala, Olli Simell, G Sebastio, Generoso Andria, Maria Pia Sperandeo, Marja-liisa Savontaus, Juha Mykkanen, Paolo Gasparini, Pentti AulaAbstract:Lysinuric Protein Intolerance (LPI) is an autosomal recessive disorder in which transport of the cationic amino acids lysine, arginine and ornithine is defective at the basolateral membrane of the epithelial cells in the intestine and renal tubules. LPI is unusually common in Finland, but patients have been described on all continents. Linkage analysis in Finnish LPI families recently assigned the LPI gene locus to a 10 cM interval between markers D14S72 and MYH7 on the long arm of chromosome 14. In the present study linkage analysis of LPI families from six different non-Finnish populations strongly suggests genetic homogeneity in LPI. Peak lod scores were obtained at the chromosomal area between D14S72 and MYH7 with the same markers as in the Finnish families. The non-Finnish families showed no linkage disequilibrium except in an Italian family cluster, whereas strong allelic association in the Finnish families implies that LPI in Finland is caused by a founder mutation.
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human cationic amino acid transporter gene hcat 2 is assigned to 8p22 but is not the causative gene in Lysinuric Protein Intolerance
Human Genetics, 1997Co-Authors: Tuija Lauteala, Olli Simell, Marja-liisa Savontaus, Mari Lukkarinen, Nina Horellikuitunen, Ellen I Closs, James M Cunningham, Aarno Palotie, Pentti AulaAbstract:Lysinuric Protein Intolerance (LPI) is a recessively inherited amino acid disorder characterized by defective efflux of cationic amino acids at the basolateral membrane of the intestinal and renal tubular epithelium. Recently, cDNAs encoding the related Proteins hCAT-2A and hCAT-2B have been cloned. These two carrier Proteins are most likely the product of the same gene, hCAT-2. Using the hCAT-2B cDNA, we assigned the hCAT-2 gene to chromosome 8p22. Furthermore, by linkage analysis in Finnish LPI families, we ruled out that hCAT-2B is involved in LPI disease.
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Lysinuric Protein Intolerance lpi gene maps to the long arm of chromosome 14
American Journal of Human Genetics, 1997Co-Authors: Tuija Lauteala, Olli Simell, Pertti Sistonen, Marja-liisa Savontaus, Juha Mykkanen, Jaakko Simell, Mari Lukkarinen, Pentti AulaAbstract:Summary Lysinuric Protein Intolerance (LPI) is an autosomal recessive disease characterized by defective transport of cationic amino acids and by hyperammonemia. Linkage analysis in 20 Finnish LPI families assigned the LPI gene locus to the proximal long arm of chromosome 14. Recombinations placed the locus between framework markers D14S72 and MYH7, a 10-cM interval in which the markers D14S742, D14S50, D14S283, and TCRA showed no recombinations with the phenotype. The phenotype was in highly significant linkage disequilibrium with markers D14S50, D14S283, and TCRA. The strongest allelic association obtained with marker TCRA, resulting in a P excess value of .98, suggests that the LPI gene locus lies in close proximity to this marker, probably within a distance of
Tuija Lauteala - One of the best experts on this subject based on the ideXlab platform.
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characterization of the Lysinuric Protein Intolerance lpi region within t cell receptor α δ gene cluster on chromosome site 14qll
Hereditas, 2004Co-Authors: Tuija Lauteala, Olli Simell, Marja-liisa Savontaus, Juha Mykkanen, Nina Horellikuitunen, Johanna Aaltonen, Paulina Paavola, Pentti AulaAbstract:: Lysinuric Protein Intolerance is a recessively inherited metabolic disease characterized by defective efflux of cationic amino acids at the basolateral membrane of the intestinal and renal tubular epithelium. Linkage analysis and further linkage disequilibrium in Finnish LPI families have earlier assigned LPI gene locus within or in close vicinity of T-cell receptor alpha/delta gene cluster on chromosome site 14q11. In the present work we have characterized the linkage defined LPI region using RH-mapping and fiber-FISH and searched the LPI gene from the reported sequence of the T-cell receptor gene.
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Characterization of the Lysinuric Protein Intolerance (LPI) Region within T‐cell Receptor α/δ Gene Cluster on Chromosome Site 14qll
Hereditas, 2004Co-Authors: Tuija Lauteala, Olli Simell, Marja-liisa Savontaus, Juha Mykkanen, Johanna Aaltonen, Paulina Paavola, Nina Horelli-kuitunen, Pentti AulaAbstract:: Lysinuric Protein Intolerance is a recessively inherited metabolic disease characterized by defective efflux of cationic amino acids at the basolateral membrane of the intestinal and renal tubular epithelium. Linkage analysis and further linkage disequilibrium in Finnish LPI families have earlier assigned LPI gene locus within or in close vicinity of T-cell receptor alpha/delta gene cluster on chromosome site 14q11. In the present work we have characterized the linkage defined LPI region using RH-mapping and fiber-FISH and searched the LPI gene from the reported sequence of the T-cell receptor gene.
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genetic homogeneity of Lysinuric Protein Intolerance
European Journal of Human Genetics, 1998Co-Authors: Tuija Lauteala, Olli Simell, G Sebastio, Generoso Andria, Maria Pia Sperandeo, Marja-liisa Savontaus, Juha Mykkanen, Paolo Gasparini, Pentti AulaAbstract:Lysinuric Protein Intolerance (LPI) is an autosomal recessive disorder in which transport of the cationic amino acids lysine, arginine and ornithine is defective at the basolateral membrane of the epithelial cells in the intestine and renal tubules. LPI is unusually common in Finland, but patients have been described on all continents. Linkage analysis in Finnish LPI families recently assigned the LPI gene locus to a 10 cM interval between markers D14S72 and MYH7 on the long arm of chromosome 14. In the present study linkage analysis of LPI families from six different non-Finnish populations strongly suggests genetic homogeneity in LPI. Peak lod scores were obtained at the chromosomal area between D14S72 and MYH7 with the same markers as in the Finnish families. The non-Finnish families showed no linkage disequilibrium except in an Italian family cluster, whereas strong allelic association in the Finnish families implies that LPI in Finland is caused by a founder mutation.
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Varicella and varicella immunity in patients with Lysinuric Protein Intolerance
Journal of Inherited Metabolic Disease, 1998Co-Authors: M. Lukkarinen, Tuija Lauteala, Matti Nuutinen, K. Näntö-salonen, O. Ruuskanen, S. Säkö, O. SimellAbstract:Two patients with Lysinuric Protein Intolerance (LPI) had near-fatal generalized varicella infection with severe interstitial pneumonitis, hepatitis, decreased platelet count, bleeding and hypoalbuminaemia. Active haemolysis resulted in anaemia and massive haemoglobinuria. Serum lactate dehydrogenase activity and ferritin concentration, which in patients with LPI in normal circumstances exceed the upper reference values 3-fold to 10-fold, increased to >10 000U/L and >10 000 µg/L, respectively. The patients were treated with fresh frozen plasma, red-cell transfusions and intravenous acyclovir for 14 days, and recovered clinically in a month. Retrospectively, 3 of the 32 other known Finnish patients with LPI had had varicella infection that had been more severe than that in the other children in the family or in subjects in the neighbourhood and had led to hospital admission. Varicella antibodies were measured in 24 patients; 5 had no antibodies and 5 had very low antibody titres. Primary vaccination of three patients with living varicella vaccine increased antibody titres measurably in one patient. We suggest that patients with LPI who have no varicella zoster antibodies should be treated with acyclovir if exposed to varicella and should be (re)vaccinated against chickenpox.
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Lysinuric Protein Intolerance (LPI) GeneMapstotheLongArmof Chromosome14
1997Co-Authors: Tuija Lauteala, Pertti Sistonen, Marja-liisa SavontausAbstract:Summary Lysinuric Protein Intolerance (LPI) isanautosomal recessive disease characterized bydefective transport of cationic aminoacids andbyhyperammonemia. Linkage analysis in20Finnish LPIfamilies assigned theLPIgene locus totheproximal long armofchromosome 14.Recombinations placed thelocus between framework markers D14S72andMYH7,a10-cMinterval inwhich themarkers D14S742, D14S50, D14S283, andTCRA showed norecombinations withthephenotype. The phenotype wasinhighly significant linkage disequilibriumwithmarkers D14S50, D14S283, andTCRA.The strongest allelic association obtained withmarker TCRA,resulting inaPexcess value of.98, suggests that theLPIgenelocus lies inclose proximity tothis marker, probably within adistance of
