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http://purl.uniprot.org/citations/24423360http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/24423360http://www.w3.org/2000/01/rdf-schema#comment"

Context

Acid labile subunit (ALS) deficiency, caused by IGFALS mutations, is a subtype of primary IGF-I deficiency (PIGFD) and has been associated with insulin resistance (IR) and osteopenia. Whether patients respond to recombinant human IGF-I (rhIGF-I) is unknown.

Objective and design

This study determined the 14-hour pharmacokinetic response of free and total IGF-I and IGF binding protein 3 (IGFBP-3) to a single sc dose of rhIGF-I (120 μg/kg) in four ALS-deficient patients, compared with severe PIGFD, moderate PIGFD, and controls. Intravenous glucose tolerance tests, fasting blood levels, dual-energy X-ray absorptiometry, peripheral quantitative computed tomography, and metacarpal radiogrammetry were performed in the four patients and 12 heterozygous family members.

Results

IGF-I and IGFBP-3 increased above baseline (P < .05) for 2.5 hours, returning to baseline 7 hours after rhIGF-I injection. Mean (SD) IGF-I Z-score increased by 2.49 (0.90), whereas IGFBP-3 Z-score increased by 0.57 (0.10) only. IGF-I elimination rates in ALS deficiency were similar, but the IGF-I increment was lower than those for severe PIGFD. Significant gene dosage effects were found for all IGF-I peptides, height, forearm muscle size, and metacarpal width. Bone analysis showed that ALS deficiency creates a phenotype of slender bones with normal size-corrected density. Abnormal glucose handling and IR was found in three of four patients and 6 of 12 carriers.

Conclusions

These gene dosage effects demonstrate that one functional IGFALS allele is insufficient to maintain normal ALS levels, endocrine IGF-I action, full growth potential, muscle size, and periosteal expansion. Similar gene dosage effects may exist for parameters of IR. Despite similar IGF-I elimination compared with severe PIGFD, ALS-deficient patients cannot mount a similar response. Alternative ways of rhIGF-I administration should be sought."xsd:string
http://purl.uniprot.org/citations/24423360http://purl.org/dc/terms/identifier"doi:10.1210/jc.2013-3718"xsd:string
http://purl.uniprot.org/citations/24423360http://purl.uniprot.org/core/author"Martin D.D."xsd:string
http://purl.uniprot.org/citations/24423360http://purl.uniprot.org/core/author"Shaw N."xsd:string
http://purl.uniprot.org/citations/24423360http://purl.uniprot.org/core/author"Rose S."xsd:string
http://purl.uniprot.org/citations/24423360http://purl.uniprot.org/core/author"Barrett T."xsd:string
http://purl.uniprot.org/citations/24423360http://purl.uniprot.org/core/author"Hwa V."xsd:string
http://purl.uniprot.org/citations/24423360http://purl.uniprot.org/core/author"Walker J."xsd:string
http://purl.uniprot.org/citations/24423360http://purl.uniprot.org/core/author"Tomlinson J."xsd:string
http://purl.uniprot.org/citations/24423360http://purl.uniprot.org/core/author"Frystyk J."xsd:string
http://purl.uniprot.org/citations/24423360http://purl.uniprot.org/core/author"Hogler W."xsd:string
http://purl.uniprot.org/citations/24423360http://purl.uniprot.org/core/author"Rosenfeld R."xsd:string
http://purl.uniprot.org/citations/24423360http://purl.uniprot.org/core/author"Metherell L."xsd:string
http://purl.uniprot.org/citations/24423360http://purl.uniprot.org/core/author"Nightingale P."xsd:string
http://purl.uniprot.org/citations/24423360http://purl.uniprot.org/core/author"Crabtree N."xsd:string
http://purl.uniprot.org/citations/24423360http://purl.uniprot.org/core/date"2014"xsd:gYear
http://purl.uniprot.org/citations/24423360http://purl.uniprot.org/core/name"J Clin Endocrinol Metab"xsd:string
http://purl.uniprot.org/citations/24423360http://purl.uniprot.org/core/pages"E703-12"xsd:string
http://purl.uniprot.org/citations/24423360http://purl.uniprot.org/core/title"IGFALS gene dosage effects on serum IGF-I and glucose metabolism, body composition, bone growth in length and width, and the pharmacokinetics of recombinant human IGF-I administration."xsd:string
http://purl.uniprot.org/citations/24423360http://purl.uniprot.org/core/volume"99"xsd:string
http://purl.uniprot.org/citations/24423360http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/24423360
http://purl.uniprot.org/citations/24423360http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/24423360
http://purl.uniprot.org/uniprot/#_B0AZL7-mappedCitation-24423360http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24423360
http://purl.uniprot.org/uniprot/#_P35858-mappedCitation-24423360http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24423360
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