Patients with IGHD type IB are characterized by low but detectable levels of GH, short stature, significantly retarded bone age, and a positive response and immunologic tolerance to GH therapy.
See entry 262400 for a summary ... Patients with IGHD type IB are characterized by low but detectable levels of GH, short stature, significantly retarded bone age, and a positive response and immunologic tolerance to GH therapy. See entry 262400 for a summary of the different types of IGHD.
Wajnrajch et al. (1996) described 2 first cousins, a boy and a girl, from a consanguineous Indian Moslem kindred with the typical phenotype of severe growth hormone deficiency (isolated growth hormone deficiency IB). The 3.5-year-old girl and her ... Wajnrajch et al. (1996) described 2 first cousins, a boy and a girl, from a consanguineous Indian Moslem kindred with the typical phenotype of severe growth hormone deficiency (isolated growth hormone deficiency IB). The 3.5-year-old girl and her 16-year-old cousin had shown poor growth since infancy and both were extremely short. They were prepubertal with frontal bossing and predominantly truncal obesity. Both failed to produce growth hormone in response to standard provocative tests and to repetitive stimulation with growth hormone-releasing hormone (GHRH; 139190). They responded to administration of growth hormone (GH; 139250). Salvatori et al. (1999) reported members of a large extended pedigree with familial dwarfism from Itabaianinha, a rural county in the state of Sergipe, located in northeastern Brazil. Inhabitants of this region are thought to be of Portuguese descent. They have a high frequency of consanguineous marriages. The diagnosis of dwarfism was based on early growth failure, proportionate short stature, and radiologic evidence of delayed bone age. Affected subjects were very short and attained an adult stature that ranged between 105 and 135 cm. In addition, patients had high-pitched voices and increased abdominal fat accumulation. Except for a somewhat delayed onset of puberty, which did not affect their fertility, they did not manifest any signs or symptoms that suggest deficiency of other pituitary hormones. Ten patients were treated with recombinant human growth hormone for 1 year, and each showed a brisk increase in growth velocity without reduced responsiveness over time. Menezes Oliveira et al. (2006) studied the consequences of lifetime isolated GHD (IGHD) on the metabolic and cardiovascular status of adult members of a large Brazilian kindred (Itabaianinha cohort) with severe IGHD due to a homozygous mutation in the GHRHR gene (139191.0002). GHD subjects had increased abdominal obesity, higher total and low density lipoprotein cholesterol, and higher C-reactive protein (123260) than controls. They did not have an increase in carotid wall thickness, and there was no evidence of premature atherosclerosis as evaluated by exercise echocardiography. The authors concluded that in this homogeneous cohort, untreated severe IGHD is not associated with evidence of premature atherosclerosis despite unfavorable cardiovascular risk profile.
In at least 2 members of a consanguineous family with profound growth hormone deficiency, Wajnrajch et al. (1996) demonstrated a nonsense mutation in the human GHRHR gene (139191.0001). The phenotype in this Indian Moslem kindred was comparable to ... In at least 2 members of a consanguineous family with profound growth hormone deficiency, Wajnrajch et al. (1996) demonstrated a nonsense mutation in the human GHRHR gene (139191.0001). The phenotype in this Indian Moslem kindred was comparable to that in the 'little' mouse, which carries a mutation in the growth hormone-releasing factor receptor (Ghrfr). The authors pointed out that other members of the G protein-coupled receptor superfamily are subject to mutations that can cause an increase in ligand-mediated signaling or constitutive receptor activation and resulted in hyperfunction of target cells. Endocrine disorders resulting from such activating mutations include familial male precocious puberty (176410) caused by mutation in the LH receptor (152790), Jansen metaphyseal dysplasia with hypercalcemia (156400) caused by mutation in the PTH receptor (168468), and hyperparathyroidism caused by mutation in the calcium-sensing receptor (145980.0004). Wajnrajch et al. (1996) suggested that analogous mutations in the GHRHR gene should be sought in patients with excessive production of growth hormone causing gigantism or acromegaly. Leiberman et al. (2000) demonstrated that heterozygosity for a splice site mutation causing autosomal recessive growth hormone deficiency in an inbred Bedouin kindred (139250.0015) was associated with short stature in carriers who were found normal on pharmacologic stimulation for GH release. Aguiar-Oliveira et al. (1999) measured IGF1, IGF2 (147470), IGF-binding protein-1 (IGFBP1; 146730), IGFBP2 (146731), IGFBP3, and acid labile subunit (ALS; 601489) in 27 subjects with GHD (aged 5 to 82 years) from an extended kindred in Northeast Brazil with the intron 1 splice site GHRHR mutation (139191.0002) and in 55 indigenous controls (aged 5 to 80 years). All components of the IGF axis, measured and theoretical, showed complete separation between GHD and control subjects, except IGFBP1 and IGFBP2 concentrations, which did not differ. The most profound effects of GHD were on total IGF1, IGF1 in the ternary complex, and ALS. The proportion of IGF1 associated with IGFBP3 remained constant throughout life, but was significantly lower in GHD due to an increase in IGF1/IGFBP2 complexes. As diagnostic tests, IGF1 in the ternary complex and total IGF1 provided the greatest separation between GHD and controls in childhood. The authors concluded that severe GHD not only reduces the amounts of IGFs, IGFBP3, and ALS, but also modifies the distribution of the IGFs bound to each IGFBP.