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http://purl.uniprot.org/citations/35089870http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/35089870http://www.w3.org/2000/01/rdf-schema#comment"

Objective

The phenotype mediated by HNF4A/HNF1A mutations is variable and includes diazoxide-responsive hyperinsulinaemic hypoglycaemia (HH) and maturity-onset diabetes of the young (MODY).

Design

We characterised an international multicentre paediatric cohort of patients with HNF4Aor HNF1Amutations presenting with HH over a 25-year period (1995-2020).

Methods

Clinical and genetic analysis data from five centres were obtained. Diazoxide responsiveness was defined as the ability to maintain normoglycaemia without intravenous glucose. Macrosomia was defined as a birth weight ≥90th centile. SPSS v.27.1 was used for data analysis.

Results

A total of 34 patients (70.6% female, n = 24) with a mean age of 7.1 years (s.d. 6.4) were included. A total of 21 different heterozygous HNF4Amutations were identified in 29 patients (four novels). Four different previously described heterozygous HNF1A mutations were detected in five patients. Most (97.1%, n = 33) developed hypoglycaemia by day 2 of life. The mean birth weight was 3.8 kg (s.d. 0.8), with most infants macrosomic (n = 21, 61.8%). Diazoxide was commenced in 28 patients (82.3%); all responded. HH resolved in 20 patients (58.8%) following a median of 0.9 years (interquartile range (IQR): 0.2-6.8). Nine patients (n = 9, 26.5%) had developmental delay. Two patients developed Fanconi syndrome (p.Arg63Trp, HNF4A) and four had other renal or hepatic findings. Five (14.7%) developed MODY at a median of 11.0 years (IQR: 9.0-13.9). Of patients with inherited mutations (n = 25, 73.5%), a family history of diabetes was present in 22 (88.0%).

Conclusions

We build on the knowledge of the natural history and pancreatic and extra-pancreatic phenotypes of HNF4A/HNF1Amutations and illustrate the heterogeneity of this condition."xsd:string
http://purl.uniprot.org/citations/35089870http://purl.org/dc/terms/identifier"doi:10.1530/eje-21-0897"xsd:string
http://purl.uniprot.org/citations/35089870http://purl.uniprot.org/core/author"Shah P."xsd:string
http://purl.uniprot.org/citations/35089870http://purl.uniprot.org/core/author"Flanagan S.E."xsd:string
http://purl.uniprot.org/citations/35089870http://purl.uniprot.org/core/author"Brusgaard K."xsd:string
http://purl.uniprot.org/citations/35089870http://purl.uniprot.org/core/author"Demirbilek H."xsd:string
http://purl.uniprot.org/citations/35089870http://purl.uniprot.org/core/author"Murphy N.P."xsd:string
http://purl.uniprot.org/citations/35089870http://purl.uniprot.org/core/author"McGlacken-Byrne S.M."xsd:string
http://purl.uniprot.org/citations/35089870http://purl.uniprot.org/core/author"Dastamani A."xsd:string
http://purl.uniprot.org/citations/35089870http://purl.uniprot.org/core/author"Conlon N."xsd:string
http://purl.uniprot.org/citations/35089870http://purl.uniprot.org/core/author"Houghton J.A.L."xsd:string
http://purl.uniprot.org/citations/35089870http://purl.uniprot.org/core/author"Schou A.J."xsd:string
http://purl.uniprot.org/citations/35089870http://purl.uniprot.org/core/author"Christesen H."xsd:string
http://purl.uniprot.org/citations/35089870http://purl.uniprot.org/core/author"Gubaeva D."xsd:string
http://purl.uniprot.org/citations/35089870http://purl.uniprot.org/core/author"Melikyan M."xsd:string
http://purl.uniprot.org/citations/35089870http://purl.uniprot.org/core/author"Mohammad J.K."xsd:string
http://purl.uniprot.org/citations/35089870http://purl.uniprot.org/core/author"Siersbaek J."xsd:string
http://purl.uniprot.org/citations/35089870http://purl.uniprot.org/core/date"2022"xsd:gYear
http://purl.uniprot.org/citations/35089870http://purl.uniprot.org/core/name"Eur J Endocrinol"xsd:string
http://purl.uniprot.org/citations/35089870http://purl.uniprot.org/core/pages"417-427"xsd:string
http://purl.uniprot.org/citations/35089870http://purl.uniprot.org/core/title"Clinical and genetic heterogeneity of HNF4A/HNF1A mutations in a multicentre paediatric cohort with hyperinsulinaemic hypoglycaemia."xsd:string
http://purl.uniprot.org/citations/35089870http://purl.uniprot.org/core/volume"186"xsd:string
http://purl.uniprot.org/citations/35089870http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/35089870
http://purl.uniprot.org/citations/35089870http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/35089870
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