title: Hypogonadotropic Hypogonadism and Short Stature in Patients with Diabetes Due to Neurogenin 3 Deficiency.
abstract: Biallelic mutations in NEUROG3 are known to cause early-onset malabsorptive diarrhea due to congenital anendocrinosis and diabetes mellitus at a variable age. No other endocrine disorders have been described so far. We report four patients with homozygous NEUROG3 mutations who presented with short stature and failed to show any signs of pubertal development.
  
  
  
  Four patients (two males, two females) were diagnosed with homozygous mutations in NEUROG3 on the basis of congenital malabsorptive diarrhea and diabetes. All four had severe short stature and failed to develop secondary sexual characteristics at an appropriate age, despite some having normal body mass index. The absence of gonadal function persisted into the third decade in one patient. Upon testing, both basal and stimulated LH and FSH levels were low, with the remaining pituitary hormones within the normal range. Magnetic resonance imaging scans of the hypothalamic-pituitary axis did not reveal structural abnormalities. A diagnosis of hypogonadotropic hypogonadism was made, and replacement therapy with sex hormones was started.
  
  
  
  The high reproducibility of this novel phenotype suggests that central hypogonadism and short stature are common findings in patients with mutations in NEUROG3. Growth rate needs to be carefully monitored in these patients, who also should be routinely screened for hypogonadism when they reach the appropriate age. NEUROG3 mutations expand on the growing number of genetic causes of acquired hypogonadotropic hypogonadism.
authors.affiliation: Department of Pediatric Endocrinology (O.R.-C.), Hospital Infantil Universitario Niño Jesús, Instituto de Investigación Sanitaria La Princesa, 28007 Madrid, Spain; Department of Pediatrics (J.L.G.), Complejo Hospitalario Torrecárdenas, 04009 Almería, Spain; Department of Pediatrics (A.G.), University of Concepcion, School of Medicine, 4070038 Concepción, Chile; Institute for Biomedical and Clinical Science (A.T.H.), University of Exeter Medical School, Exeter EX2 5DW, United Kingdom; and Institute of Maternal and Child Research (E.C.), School of Medicine, University of Chile, 8360160 Santiago, Chile.
authors.forename: Oscar
authors.initials: O
authors.lastname: Rubio-Cabezas
authors.affiliation: Department of Pediatric Endocrinology (O.R.-C.), Hospital Infantil Universitario Niño Jesús, Instituto de Investigación Sanitaria La Princesa, 28007 Madrid, Spain; Department of Pediatrics (J.L.G.), Complejo Hospitalario Torrecárdenas, 04009 Almería, Spain; Department of Pediatrics (A.G.), University of Concepcion, School of Medicine, 4070038 Concepción, Chile; Institute for Biomedical and Clinical Science (A.T.H.), University of Exeter Medical School, Exeter EX2 5DW, United Kingdom; and Institute of Maternal and Child Research (E.C.), School of Medicine, University of Chile, 8360160 Santiago, Chile.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Gómez
authors.affiliation: Department of Pediatric Endocrinology (O.R.-C.), Hospital Infantil Universitario Niño Jesús, Instituto de Investigación Sanitaria La Princesa, 28007 Madrid, Spain; Department of Pediatrics (J.L.G.), Complejo Hospitalario Torrecárdenas, 04009 Almería, Spain; Department of Pediatrics (A.G.), University of Concepcion, School of Medicine, 4070038 Concepción, Chile; Institute for Biomedical and Clinical Science (A.T.H.), University of Exeter Medical School, Exeter EX2 5DW, United Kingdom; and Institute of Maternal and Child Research (E.C.), School of Medicine, University of Chile, 8360160 Santiago, Chile.
authors.forename: Andrea
authors.initials: A
authors.lastname: Gleisner
authors.affiliation: Department of Pediatric Endocrinology (O.R.-C.), Hospital Infantil Universitario Niño Jesús, Instituto de Investigación Sanitaria La Princesa, 28007 Madrid, Spain; Department of Pediatrics (J.L.G.), Complejo Hospitalario Torrecárdenas, 04009 Almería, Spain; Department of Pediatrics (A.G.), University of Concepcion, School of Medicine, 4070038 Concepción, Chile; Institute for Biomedical and Clinical Science (A.T.H.), University of Exeter Medical School, Exeter EX2 5DW, United Kingdom; and Institute of Maternal and Child Research (E.C.), School of Medicine, University of Chile, 8360160 Santiago, Chile.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Hattersley
authors.affiliation: Department of Pediatric Endocrinology (O.R.-C.), Hospital Infantil Universitario Niño Jesús, Instituto de Investigación Sanitaria La Princesa, 28007 Madrid, Spain; Department of Pediatrics (J.L.G.), Complejo Hospitalario Torrecárdenas, 04009 Almería, Spain; Department of Pediatrics (A.G.), University of Concepcion, School of Medicine, 4070038 Concepción, Chile; Institute for Biomedical and Clinical Science (A.T.H.), University of Exeter Medical School, Exeter EX2 5DW, United Kingdom; and Institute of Maternal and Child Research (E.C.), School of Medicine, University of Chile, 8360160 Santiago, Chile.
authors.forename: Ethel
authors.initials: E
authors.lastname: Codner
mesh_terms: D000293:Adolescent; D000328:Adult; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency*; D003920:Diabetes Mellitus / Q000235:genetics*; D012734:Disorders of Sex Development / Q000235:genetics*; D004392:Dwarfism / Q000235:genetics*; D005260:Female; D006801:Humans; D007006:Hypogonadism / Q000235:genetics*; D008297:Male; D009419:Nerve Tissue Proteins / Q000172:deficiency*; D055815:Young Adult
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; C498695:NEUROG3 protein, human