title: Two siblings with isolated GH deficiency due to loss-of-function mutation in the GHRHR gene: successful treatment with growth hormone despite late admission and severe growth retardation.
abstract: Patients with growth hormone releasing hormone receptor (GHRHR) mutations exhibit pronounced dwarfism and are phenotypically and biochemically indistinguishable from other forms of isolated growth hormone deficiency (IGHD). We presented here two siblings with clinical findings of IGHD due to a nonsense mutation in the GHRHR gene who reached their target height in spite of late GH treatment. Two female siblings were admitted to our clinic with severe short stature at the age of 13.8 (patient 1) and 14.8 years (patient 2). On admission, height in patient 1 was 107 cm (-8.6 SD) and 117 cm (-6.7 SD) in patient 2. Bone age was delayed in both patients (6 years and 9 years). Clinical and biochemical analyses revealed a diagnosis of complete IGHD (peak GH levels on stimulation test was 0.06 ng/mL in patient 1 and 0.16 ng/mL in patient 2). Patients were given recombinant human GH treatment. Genetic analysis of the GH and GHRHR genes revealed that both patientscarried the GHRHR gene mutation p.Glu72X (c.214 G>T) in exon 3 in homozygous (or hemizygous) state. After seven years of GH treatment, the patients reached a final height appropriate for their target height. Final height was 151 cm (-1.5 SD) in patient 1 and 153 cm (-1.2 SD) in patient 2. In conclusion, genetic analysis is indicated in IGHD patients with severe growth failure and a positive family history. In spite of the very late diagnosis in these two patients who presented with severe growth deficit due to homozygous loss-of-function mutations in GHRHR, their final heights reached the target height.
authors.affiliation: Ankara University, School of Medicine, Department of Pediatrics, Division of Pediatric Endocrinology, Ankara, Turkey. zeynepsklr@gmail.com
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Sıklar
authors.forename: Merih
authors.initials: M
authors.lastname: Berberoğlu
authors.forename: Maria
authors.initials: M
authors.lastname: Legendre
authors.forename: Serge
authors.initials: S
authors.lastname: Amselem
authors.forename: Olcay
authors.initials: O
authors.lastname: Evliyaoğlu
authors.forename: Bülent
authors.initials: B
authors.lastname: Hacıhamdioğlu
authors.forename: Senay
authors.initials: S
authors.lastname: Savaş Erdeve
authors.forename: Gönül
authors.initials: G
authors.lastname: Oçal
mesh_terms: D000293:Adolescent; D000328:Adult; D001827:Body Height; D005260:Female; D005500:Follow-Up Studies; D019382:Human Growth Hormone / Q000172:deficiency* / Q000627:therapeutic use; D006801:Humans; D018013:Receptors, Neuropeptide / Q000235:genetics*; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000235:genetics*; D011994:Recombinant Proteins / Q000627:therapeutic use; D035781:Siblings
chemical_list: D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D011994:Recombinant Proteins; D019382:Human Growth Hormone; C048250:somatotropin releasing hormone receptor