6R-tetrahydrobiopterin treated PKU patients below 4 years of age: Physical outcomes, nutrition and genotype
Phenylalanine-restricted diets have proven effective in treating phenylketonuria. However, such diets have occasionally been reported to hinder normal development. Our study aimed to assess whether treating 0-4-year-old phenylketonuric patients with 6R-tetrahydrobiopterin might prevent growth retard...
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| Veröffentlicht in: | Molecular genetics and metabolism 2015-05, Vol.115 (1), p.10-16 |
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| creator | Aldámiz-Echevarría, Luis Bueno, María A Couce, María L Lage, Sergio Dalmau, Jaime Vitoria, Isidro Llarena, Marta Andrade, Fernando Blasco, Javier Alcalde, Carlos Gil, David García, María C González-Lamuño, Domingo Ruiz, Mónica Ruiz, María A Peña-Quintana, Luis González, David Sánchez-Valverde, Felix |
| description | Phenylalanine-restricted diets have proven effective in treating phenylketonuria. However, such diets have occasionally been reported to hinder normal development. Our study aimed to assess whether treating 0-4-year-old phenylketonuric patients with 6R-tetrahydrobiopterin might prevent growth retardation later in life.
We conducted a longitudinal retrospective study which examined anthropometric characteristics of phenylketonuric patients on 6R-tetrahydrobiopterin therapy (22 subjects), and compared them with a group of phenylketonuric patients on protein-restricted diets (44 subjects). Nutritional issues were also considered. We further explored possible relationships between mutations in the PAH gene, BH4 responsiveness and growth outcome.
No significant growth improvements were observed in either the group on 6R-tetrahydrobiopterin treatment (height Z-score: initial= -0.57 ± 1.54; final=-0.52 ± 1.29; BMI Z-score: initial=0.17 ± 1.05; final=0.18 ± 1.00) or the diet-only group (height Z-score: initial=-0.92 ± 0.96; final= -0.78 ± 1.08; BMI Z-score: initial=0.17 ± 0.97; final=-0.07 ± 1.03) over the 1-year observation period. Furthermore, we found no significant differences (p>0.05) between the two groups at any of the time points considered (0, 6 and 12 months). Patients on 6R-tetrahydrobiopterin increased their phenylalanine intake (from 49.1 [25.6-60.3] to 56.5 [39.8-68.3] mgkg(-1)day(-1)) and natural protein intake (from 1.0 [0.8-1.7] to 1.5 [1.0-1.8] g kg(-1)day(-1)), and some patients managed to adopt normal diets. Higher phenylalanine and natural protein intakes were positively correlated with better physical outcomes in the diet-only group (p |
| doi_str_mv | 10.1016/j.ymgme.2015.03.007 |
| format | Article |
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We conducted a longitudinal retrospective study which examined anthropometric characteristics of phenylketonuric patients on 6R-tetrahydrobiopterin therapy (22 subjects), and compared them with a group of phenylketonuric patients on protein-restricted diets (44 subjects). Nutritional issues were also considered. We further explored possible relationships between mutations in the PAH gene, BH4 responsiveness and growth outcome.
No significant growth improvements were observed in either the group on 6R-tetrahydrobiopterin treatment (height Z-score: initial= -0.57 ± 1.54; final=-0.52 ± 1.29; BMI Z-score: initial=0.17 ± 1.05; final=0.18 ± 1.00) or the diet-only group (height Z-score: initial=-0.92 ± 0.96; final= -0.78 ± 1.08; BMI Z-score: initial=0.17 ± 0.97; final=-0.07 ± 1.03) over the 1-year observation period. Furthermore, we found no significant differences (p>0.05) between the two groups at any of the time points considered (0, 6 and 12 months). Patients on 6R-tetrahydrobiopterin increased their phenylalanine intake (from 49.1 [25.6-60.3] to 56.5 [39.8-68.3] mgkg(-1)day(-1)) and natural protein intake (from 1.0 [0.8-1.7] to 1.5 [1.0-1.8] g kg(-1)day(-1)), and some patients managed to adopt normal diets. Higher phenylalanine and natural protein intakes were positively correlated with better physical outcomes in the diet-only group (p<0.05). No correlation was found between patient genotype and physical outcomes, results being similar regardless of the nutritional approach used. We did not detect any side effects due to 6R-tetrahydrobiopterin administration.
Our study indicates that treating 0-4-year-old phenylketonuric patients with 6R-tetrahydrobiopterin is safe. However, poor developmental outcomes were observed, despite increasing the intake of natural proteins. Genotype could be a valid predictor of tetrahydrobiopterin-responsiveness, since patients who carried the same genotype responded similarly to the 6R-tetrahydrobiopterin loading test. On the other hand, harbouring 6R-tetrahydrobiopterin responsive genotypes did not predispose patients to better physical outcomes.</description><identifier>EISSN: 1096-7206</identifier><identifier>DOI: 10.1016/j.ymgme.2015.03.007</identifier><identifier>PMID: 25882749</identifier><language>eng</language><publisher>United States</publisher><subject>Biopterins - administration & dosage ; Biopterins - analogs & derivatives ; Biopterins - therapeutic use ; Body Height ; Body Weight ; Child, Preschool ; Diet, Protein-Restricted ; Female ; Genotype ; Humans ; Infant ; Infant, Newborn ; Longitudinal Studies ; Male ; Mutation ; Nutritional Status ; Phenylalanine - administration & dosage ; Phenylalanine - blood ; Phenylketonurias - diet therapy ; Phenylketonurias - drug therapy ; Phenylketonurias - genetics ; Phenylketonurias - physiopathology ; Retrospective Studies ; Spain</subject><ispartof>Molecular genetics and metabolism, 2015-05, Vol.115 (1), p.10-16</ispartof><rights>Copyright © 2015 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25882749$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Aldámiz-Echevarría, Luis</creatorcontrib><creatorcontrib>Bueno, María A</creatorcontrib><creatorcontrib>Couce, María L</creatorcontrib><creatorcontrib>Lage, Sergio</creatorcontrib><creatorcontrib>Dalmau, Jaime</creatorcontrib><creatorcontrib>Vitoria, Isidro</creatorcontrib><creatorcontrib>Llarena, Marta</creatorcontrib><creatorcontrib>Andrade, Fernando</creatorcontrib><creatorcontrib>Blasco, Javier</creatorcontrib><creatorcontrib>Alcalde, Carlos</creatorcontrib><creatorcontrib>Gil, David</creatorcontrib><creatorcontrib>García, María C</creatorcontrib><creatorcontrib>González-Lamuño, Domingo</creatorcontrib><creatorcontrib>Ruiz, Mónica</creatorcontrib><creatorcontrib>Ruiz, María A</creatorcontrib><creatorcontrib>Peña-Quintana, Luis</creatorcontrib><creatorcontrib>González, David</creatorcontrib><creatorcontrib>Sánchez-Valverde, Felix</creatorcontrib><title>6R-tetrahydrobiopterin treated PKU patients below 4 years of age: Physical outcomes, nutrition and genotype</title><title>Molecular genetics and metabolism</title><addtitle>Mol Genet Metab</addtitle><description>Phenylalanine-restricted diets have proven effective in treating phenylketonuria. However, such diets have occasionally been reported to hinder normal development. Our study aimed to assess whether treating 0-4-year-old phenylketonuric patients with 6R-tetrahydrobiopterin might prevent growth retardation later in life.
We conducted a longitudinal retrospective study which examined anthropometric characteristics of phenylketonuric patients on 6R-tetrahydrobiopterin therapy (22 subjects), and compared them with a group of phenylketonuric patients on protein-restricted diets (44 subjects). Nutritional issues were also considered. We further explored possible relationships between mutations in the PAH gene, BH4 responsiveness and growth outcome.
No significant growth improvements were observed in either the group on 6R-tetrahydrobiopterin treatment (height Z-score: initial= -0.57 ± 1.54; final=-0.52 ± 1.29; BMI Z-score: initial=0.17 ± 1.05; final=0.18 ± 1.00) or the diet-only group (height Z-score: initial=-0.92 ± 0.96; final= -0.78 ± 1.08; BMI Z-score: initial=0.17 ± 0.97; final=-0.07 ± 1.03) over the 1-year observation period. Furthermore, we found no significant differences (p>0.05) between the two groups at any of the time points considered (0, 6 and 12 months). Patients on 6R-tetrahydrobiopterin increased their phenylalanine intake (from 49.1 [25.6-60.3] to 56.5 [39.8-68.3] mgkg(-1)day(-1)) and natural protein intake (from 1.0 [0.8-1.7] to 1.5 [1.0-1.8] g kg(-1)day(-1)), and some patients managed to adopt normal diets. Higher phenylalanine and natural protein intakes were positively correlated with better physical outcomes in the diet-only group (p<0.05). No correlation was found between patient genotype and physical outcomes, results being similar regardless of the nutritional approach used. We did not detect any side effects due to 6R-tetrahydrobiopterin administration.
Our study indicates that treating 0-4-year-old phenylketonuric patients with 6R-tetrahydrobiopterin is safe. However, poor developmental outcomes were observed, despite increasing the intake of natural proteins. Genotype could be a valid predictor of tetrahydrobiopterin-responsiveness, since patients who carried the same genotype responded similarly to the 6R-tetrahydrobiopterin loading test. On the other hand, harbouring 6R-tetrahydrobiopterin responsive genotypes did not predispose patients to better physical outcomes.</description><subject>Biopterins - administration & dosage</subject><subject>Biopterins - analogs & derivatives</subject><subject>Biopterins - therapeutic use</subject><subject>Body Height</subject><subject>Body Weight</subject><subject>Child, Preschool</subject><subject>Diet, Protein-Restricted</subject><subject>Female</subject><subject>Genotype</subject><subject>Humans</subject><subject>Infant</subject><subject>Infant, Newborn</subject><subject>Longitudinal Studies</subject><subject>Male</subject><subject>Mutation</subject><subject>Nutritional Status</subject><subject>Phenylalanine - administration & dosage</subject><subject>Phenylalanine - blood</subject><subject>Phenylketonurias - diet therapy</subject><subject>Phenylketonurias - drug therapy</subject><subject>Phenylketonurias - genetics</subject><subject>Phenylketonurias - physiopathology</subject><subject>Retrospective Studies</subject><subject>Spain</subject><issn>1096-7206</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo10E1Lw0AUheFBEFurv0CQWbow8d7J57iT4hcWLGLXYZK5aVOTTJyZIPn3Fqyrs3l4F4exK4QQAdO7fTh1245CAZiEEIUA2QmbI8g0yASkM3bu3B4AMZHxGZuJJM9FFss5-0o_Ak_eqt2krSkbM3iyTc-9JeVJ8_Xbhg_KN9R7x0tqzQ-P-UTKOm5qrrZ0z9e7yTWVarkZfWU6cre8H71tfGN6rnrNt9QbPw10wU5r1Tq6PO6CbZ4eP5cvwer9-XX5sAoGjNEHNehcJ5glJGUqRVRVItEoJWGK6iC0yHLUWS2FglSigrLUkECusYogxjxasJu_7mDN90jOF13jKmpb1ZMZXYFpDoe8SKIDvT7SsexIF4NtOmWn4v-g6BdKKmd-</recordid><startdate>201505</startdate><enddate>201505</enddate><creator>Aldámiz-Echevarría, Luis</creator><creator>Bueno, María A</creator><creator>Couce, María L</creator><creator>Lage, Sergio</creator><creator>Dalmau, Jaime</creator><creator>Vitoria, Isidro</creator><creator>Llarena, Marta</creator><creator>Andrade, Fernando</creator><creator>Blasco, Javier</creator><creator>Alcalde, Carlos</creator><creator>Gil, David</creator><creator>García, María C</creator><creator>González-Lamuño, Domingo</creator><creator>Ruiz, Mónica</creator><creator>Ruiz, María A</creator><creator>Peña-Quintana, Luis</creator><creator>González, David</creator><creator>Sánchez-Valverde, Felix</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>201505</creationdate><title>6R-tetrahydrobiopterin treated PKU patients below 4 years of age: Physical outcomes, nutrition and genotype</title><author>Aldámiz-Echevarría, Luis ; Bueno, María A ; Couce, María L ; Lage, Sergio ; Dalmau, Jaime ; Vitoria, Isidro ; Llarena, Marta ; Andrade, Fernando ; Blasco, Javier ; Alcalde, Carlos ; Gil, David ; García, María C ; González-Lamuño, Domingo ; Ruiz, Mónica ; Ruiz, María A ; Peña-Quintana, Luis ; González, David ; Sánchez-Valverde, Felix</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p141t-f0d8d5175e996923cc25d199e161a141d2781d7f92a0691a0bbd0508d1c304183</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Biopterins - administration & dosage</topic><topic>Biopterins - analogs & derivatives</topic><topic>Biopterins - therapeutic use</topic><topic>Body Height</topic><topic>Body Weight</topic><topic>Child, Preschool</topic><topic>Diet, Protein-Restricted</topic><topic>Female</topic><topic>Genotype</topic><topic>Humans</topic><topic>Infant</topic><topic>Infant, Newborn</topic><topic>Longitudinal Studies</topic><topic>Male</topic><topic>Mutation</topic><topic>Nutritional Status</topic><topic>Phenylalanine - administration & dosage</topic><topic>Phenylalanine - blood</topic><topic>Phenylketonurias - diet therapy</topic><topic>Phenylketonurias - drug therapy</topic><topic>Phenylketonurias - genetics</topic><topic>Phenylketonurias - physiopathology</topic><topic>Retrospective Studies</topic><topic>Spain</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Aldámiz-Echevarría, Luis</creatorcontrib><creatorcontrib>Bueno, María A</creatorcontrib><creatorcontrib>Couce, María L</creatorcontrib><creatorcontrib>Lage, Sergio</creatorcontrib><creatorcontrib>Dalmau, Jaime</creatorcontrib><creatorcontrib>Vitoria, Isidro</creatorcontrib><creatorcontrib>Llarena, Marta</creatorcontrib><creatorcontrib>Andrade, Fernando</creatorcontrib><creatorcontrib>Blasco, Javier</creatorcontrib><creatorcontrib>Alcalde, Carlos</creatorcontrib><creatorcontrib>Gil, David</creatorcontrib><creatorcontrib>García, María C</creatorcontrib><creatorcontrib>González-Lamuño, Domingo</creatorcontrib><creatorcontrib>Ruiz, Mónica</creatorcontrib><creatorcontrib>Ruiz, María A</creatorcontrib><creatorcontrib>Peña-Quintana, Luis</creatorcontrib><creatorcontrib>González, David</creatorcontrib><creatorcontrib>Sánchez-Valverde, Felix</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular genetics and metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Aldámiz-Echevarría, Luis</au><au>Bueno, María A</au><au>Couce, María L</au><au>Lage, Sergio</au><au>Dalmau, Jaime</au><au>Vitoria, Isidro</au><au>Llarena, Marta</au><au>Andrade, Fernando</au><au>Blasco, Javier</au><au>Alcalde, Carlos</au><au>Gil, David</au><au>García, María C</au><au>González-Lamuño, Domingo</au><au>Ruiz, Mónica</au><au>Ruiz, María A</au><au>Peña-Quintana, Luis</au><au>González, David</au><au>Sánchez-Valverde, Felix</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>6R-tetrahydrobiopterin treated PKU patients below 4 years of age: Physical outcomes, nutrition and genotype</atitle><jtitle>Molecular genetics and metabolism</jtitle><addtitle>Mol Genet Metab</addtitle><date>2015-05</date><risdate>2015</risdate><volume>115</volume><issue>1</issue><spage>10</spage><epage>16</epage><pages>10-16</pages><eissn>1096-7206</eissn><abstract>Phenylalanine-restricted diets have proven effective in treating phenylketonuria. However, such diets have occasionally been reported to hinder normal development. Our study aimed to assess whether treating 0-4-year-old phenylketonuric patients with 6R-tetrahydrobiopterin might prevent growth retardation later in life.
We conducted a longitudinal retrospective study which examined anthropometric characteristics of phenylketonuric patients on 6R-tetrahydrobiopterin therapy (22 subjects), and compared them with a group of phenylketonuric patients on protein-restricted diets (44 subjects). Nutritional issues were also considered. We further explored possible relationships between mutations in the PAH gene, BH4 responsiveness and growth outcome.
No significant growth improvements were observed in either the group on 6R-tetrahydrobiopterin treatment (height Z-score: initial= -0.57 ± 1.54; final=-0.52 ± 1.29; BMI Z-score: initial=0.17 ± 1.05; final=0.18 ± 1.00) or the diet-only group (height Z-score: initial=-0.92 ± 0.96; final= -0.78 ± 1.08; BMI Z-score: initial=0.17 ± 0.97; final=-0.07 ± 1.03) over the 1-year observation period. Furthermore, we found no significant differences (p>0.05) between the two groups at any of the time points considered (0, 6 and 12 months). Patients on 6R-tetrahydrobiopterin increased their phenylalanine intake (from 49.1 [25.6-60.3] to 56.5 [39.8-68.3] mgkg(-1)day(-1)) and natural protein intake (from 1.0 [0.8-1.7] to 1.5 [1.0-1.8] g kg(-1)day(-1)), and some patients managed to adopt normal diets. Higher phenylalanine and natural protein intakes were positively correlated with better physical outcomes in the diet-only group (p<0.05). No correlation was found between patient genotype and physical outcomes, results being similar regardless of the nutritional approach used. We did not detect any side effects due to 6R-tetrahydrobiopterin administration.
Our study indicates that treating 0-4-year-old phenylketonuric patients with 6R-tetrahydrobiopterin is safe. However, poor developmental outcomes were observed, despite increasing the intake of natural proteins. Genotype could be a valid predictor of tetrahydrobiopterin-responsiveness, since patients who carried the same genotype responded similarly to the 6R-tetrahydrobiopterin loading test. On the other hand, harbouring 6R-tetrahydrobiopterin responsive genotypes did not predispose patients to better physical outcomes.</abstract><cop>United States</cop><pmid>25882749</pmid><doi>10.1016/j.ymgme.2015.03.007</doi><tpages>7</tpages></addata></record> |
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| subjects | Biopterins - administration & dosage Biopterins - analogs & derivatives Biopterins - therapeutic use Body Height Body Weight Child, Preschool Diet, Protein-Restricted Female Genotype Humans Infant Infant, Newborn Longitudinal Studies Male Mutation Nutritional Status Phenylalanine - administration & dosage Phenylalanine - blood Phenylketonurias - diet therapy Phenylketonurias - drug therapy Phenylketonurias - genetics Phenylketonurias - physiopathology Retrospective Studies Spain |
| title | 6R-tetrahydrobiopterin treated PKU patients below 4 years of age: Physical outcomes, nutrition and genotype |
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