Isolated Growth Hormone Deficiency Type IA Associated with a 45-Kilobase Gene Deletion within the Human Growth Hormone Gene Cluster in an Italian Family

Ghizzoni, Lucia; Duquesnoy, Philippe; Torresani, Toni; Vottero, Alessandra; Goossens, Michel; Bernasconi, Sergio

doi:10.1203/00006450-199411000-00021

Cited by 26 publications

(16 citation statements)

References 29 publications

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“…Birth size has been reported to be extremely heterogeneous in patients with IGHD1A and not to correlate with the deletion size (8). This is in accordance with the present report, as the birth length of our patients was identical whereas the amplitude of GH-N gene deletion was very different.…”

Section: Discussionsupporting

confidence: 83%

“…Such important differences in the outcome of adult stature as observed in these girls confirm the significant phenotypic heterogeneity of this disease, already demonstrated even in siblings with the same genotype (4,8).…”

Section: Discussionsupporting

confidence: 63%

“…A great phenotypic heterogeneity with respect to the production of antibodies has been well documented in the literature (6,9,15,16,24) and has also been shown in siblings with an identical genotypic expression (4,8). Thus, the immune response to exogenous GH is not related exclusively to the size of the gene deletion but can be secondary to other gene products as well as the human-leucocyte-antigen molecules (25).…”

Section: Discussionmentioning

confidence: 92%

“…The parents of our patients were heterozygous for the same deletion. Molecular features of this girl and her parents have already been reported in detail previously (8).…”

Section: Case Reportsmentioning

confidence: 92%

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Final height in isolated GH deficiency type 1A: effects of 5-year treatment with IGF-I

Messina

Luca

Waśniewska³

et al. 2001

European Journal of Endocrinology

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Data concerning final height (FH) in isolated growth hormone deficiency type 1A (IGHD1A) are scanty and controversial. In this paper we report the FH outcome of two girls with IGHD1A who were treated either with GH only (first patient) or with GH during the first 8 years and successively with IGF-I (second patient). In the first patient, FH was only slightly subnormal and slightly taller with respect to target height (TH). Surprisingly, FH was severely subnormal and very far from TH in the patient who underwent IGF-I therapy for .5 years: an auxological outcome similar to the one recently reported in the only two cases in the literature of patients with IGHD1A who have been treated with IGF-I until near FH achievement. We conclude that IGHD1A could have a very heterogeneous phenotypic expression in terms of FH and that IGF-I therapy, even though initiated some years before puberty onset and prolonged for more than 5 years, may not be able to ensure the normalization of height prognosis and the achievement of an FH close to TH.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 92%

“…The parents of our patients were heterozygous for the same deletion. Molecular features of this girl and her parents have already been reported in detail previously (8).…”

Section: Case Reportsmentioning

confidence: 92%

See 2 more Smart Citations

Final height in isolated GH deficiency type 1A: effects of 5-year treatment with IGF-I

Messina

Luca

Waśniewska³

et al. 2001

European Journal of Endocrinology

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“…Therefore, in an individual patient, the significance of a positive test result for anti-GH antibodies is not clear. Nevertheless, therapeutic recommendations such as pausing rhGH treatment [8, 10], changing the rhGH brand [6] and treating with recombinant human insulin-like growth factor (rhIGF)-1 instead of rhGH [4, 11] have been proposed. These recommendations, however, were not evidence based.…”

Section: Introductionmentioning

confidence: 99%

Biological Significance of Anti-GH Antibodies in Children Treated with rhGH

Binder¹,

Heidenreich²,

Schnabel³

et al. 2019

Horm Res Paediatr

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Background: The occurrence of antidrug antibodies is common in children treated with recombinant human growth hormone (rhGH). However, their clinical significance is unclear. Objective: This study aimed to examine the clinical significance of anti-GH antibodies by analyzing the phenotype of patients who tested positive in relation to the quantity of anti-GH antibodies. Method: In this laboratory-based retrospective study encompassing a time span of 6 years, all positive samples were identified, and senders were contacted. Anti-GH antibodies were measured using a radioprecipitation assay; positive samples underwent a confirmatory assay. Results: Out of a total of 104 samples from 66 patients, positive test results were found in 28 samples from 13 patients. Clinical data were available from all but one. The group with positive test results comprised 6 patients with a normal response to GH provocative tests (group A) and 6 with an insufficient response or with isolated GH deficiency (IGHD) type 1A (group B). Diagnoses in group A were neurosecretory dysfunction, bioinactive GH syndrome and constitutional delay of growth and puberty. Diagnoses in group B were IGHD type 1A, septo-optic dysplasia, and cerebral midline defect with multiple pituitary hormone deficiency. Insufficient growth response to rhGH was absent except in one sibling pair with IGHD type 1A and a patient with cerebral midline defect. These patients had the highest concentrations of anti-GH antibodies. Conclusions: The biological significance of anti-GH antibodies seems to be limited to patients with high concentrations of anti-GH antibodies. For all other patients, we recommend a careful “wait and see” strategy and monitoring antibody titers.

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