Growth retardation and growth hormone deficiency in patients with Ataxia telangiectasia

Voss, Sandra; Pietzner, Julia; Hoche, Franziska; Taylor, Alexander M.; Schubert, Ralf; Zielen, Stefan

doi:10.3109/08977194.2014.939805

Cited by 45 publications

(60 citation statements)

References 43 publications

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“…A recent study by Voss et al demonstrated severe GH deficiency in 6/10 AT patients with growth retardation (14). The same group has previously reported low IGF-I and IGFBP3 levels in their patients, deteriorating with age (8).…”

Section: Discussionmentioning

confidence: 87%

“…Our most prominent findings were growth retardation and impaired body weight. These could be attributed to oropharyngeal dysphagia, chronic pulmonary infection, and impaired glucose metabolism (14). Growth impairment preceded the impairment in weight gain.…”

Section: Discussionmentioning

confidence: 99%

“…However, after the age of 4 y, weight-SDS steadily decreased, while height-SDS did not further deteriorate. Growth retardation has been consistently described in patients with AT (1,(4)(5)(6)(7)(8)(9)(10)(11)13,14,22), usually in small series of patients, lacking longitudinal data or detailed growth patterns. Ersoy et al (4) showed an association between growth retardation and sinopulmonary infections.…”

Section: Discussionmentioning

confidence: 99%

“…Ersoy et al (4) showed an association between growth retardation and sinopulmonary infections. Poor weight gain and abnormalities of the GH-IGF-I axis have also been suggested as possible contributors (14).…”

Section: Discussionmentioning

confidence: 99%

“…However, patient series are mostly small, lacking detailed description of endocrine abnormalities, and outdated. Growth retardation has been repeatedly described in patients with AT (1,(4)(5)(6)8,12,14), and has been attributed to sinopulmonary infections (4) or to growth hormone or IGF-I deficiency (8,14). However, detailed description of growth patterns in these patients is not available.…”

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confidence: 99%

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Endocrine abnormalities in ataxia telangiectasia: findings from a national cohort

et al. 2016

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Background: Ataxia telangiectasia (AT) is a genetic multisystem disorder, presenting with progressive ataxia, immune deficiency, and propensity toward malignancy. Endocrine abnormalities (growth retardation, reproductive dysfunction, and diabetes) have been described, however detailed information regarding this aspect is lacking. We aimed to characterize endocrine anomalies and growth patterns in a large cohort of AT patients. Methods: Retrospective study comprising all 52 patients (aged 2-26.2 y) followed at a national AT Clinic. Anthropometric and laboratory measurements were extracted from the charts. results: Median height-SDS was already subnormal during infancy, remaining negative throughout follow up to adulthood. Height-SDS was more impaired than weight-SDS up to age 4 y, thereafter weight-SDS steadily decreased, resulting in progressively lower BMI-SDS. IGF-I-SDS was low (−1.53 ± 1.54), but did not correlate with height-SDS. Gonadal failure was present in all 13 females older than 10 y but only in one male. Two patients had diabetes and 10 had dyslipidemia. Vitamin D deficiency was observed in 52.2% of the evaluated patients. conclusion: Our results suggest a primary growth abnormality in AT, rather than secondary to nutritional impairment or disease severity. Sex hormone replacement should be considered for female patients. Vitamin D levels should be followed and supplementation given if needed.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Endocrine abnormalities in ataxia telangiectasia: findings from a national cohort

et al. 2016

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Simple Measurement of IgA Predicts Immunity and Mortality in Ataxia-Telangiectasia

et al. 2021

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Patients with ataxia-telangiectasia (A-T) suffer from progressive cerebellar ataxia, immunodeficiency, respiratory failure, and cancer susceptibility. From a clinical point of view, A-T patients with IgA deficiency show more symptoms and may have a poorer prognosis. In this study, we analyzed mortality and immunity data of 659 A-T patients with regard to IgA deficiency collected from the European Society for Immunodeficiencies (ESID) registry and from 66 patients with classical A-T who attended at the Frankfurt Goethe-University between 2012 and 2018. We studied peripheral B- and T-cell subsets and T-cell repertoire of the Frankfurt cohort and survival rates of all A-T patients in the ESID registry. Patients with A-T have significant alterations in their lymphocyte phenotypes. All subsets (CD3, CD4, CD8, CD19, CD4/CD45RA, and CD8/CD45RA) were significantly diminished compared to standard values. Patients with IgA deficiency (n = 35) had significantly lower lymphocyte counts compared to A-T patients without IgA deficiency (n = 31) due to a further decrease of naïve CD4 T-cells, central memory CD4 cells, and regulatory T-cells. Although both patient groups showed affected TCR-ß repertoires compared to controls, no differences could be detected between patients with and without IgA deficiency. Overall survival of patients with IgA deficiency was significantly diminished. For the first time, our data show that patients with IgA deficiency have significantly lower lymphocyte counts and subsets, which are accompanied with reduced survival, compared to A-T patients without IgA deficiency. IgA, a simple surrogate marker, is indicating the poorest prognosis for classical A-T patients. Both non-interventional clinical trials were registered at clinicaltrials.gov 2012 (Susceptibility to infections in ataxia-telangiectasia; NCT02345135) and 2017 (Susceptibility to Infections, tumor risk and liver disease in patients with ataxia-telangiectasia; NCT03357978)

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Altered Cerebrospinal Fluid (CSF) in Children with Ataxia Telangiectasia

et al. 2020

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Ataxia telangiectasia (A-T) is a devastating multi-system disorder characterized by progressive cerebellar ataxia and immunodeficiency. The neurological decline may be caused by multiple factors of which ongoing inflammation and oxidative stress may play a dominant role. The objective of the present investigation was to determine cerebrospinal fluid (CSF) proteins and possible low-grade inflammation and its relation to age and neurological deterioration. In the present study, we investigated 15 patients with AT from 2 to 16 years. Our investigation included blood and CSF tests, clinical neurological examination, AT score, and MRI findings. The albumin ratio (AR) was analyzed to determine the blood-brain-barrier function. In addition, inflammatory cytokines (IL-1α, IL-6, IL-8, IL-12 p40, IL-17A, IFN-γ, TNF-α) were measured by the multiplex cytometric bead array. We compared the results with those from an age-matched control group. Three of the AT patients were analyzed separately (one after resection of a cerebral meningioma, one after radiation and chemotherapy due to leukemia, one after stem cell transplantation). Patient had significantly more moderate and severe side effects due to CSF puncture (vomiting, headache, need for anti-emetic drugs) compared with healthy controls. Total protein, albumin, and the AR increased with age indicating a disturbed blood barrier function in older children. There were no differences for cytokines in serum and CSF with the exception of IL-2, which was significantly higher in controls in serum. The AR is significantly altered in AT patients, but low-grade inflammation is not detectable in serum and CSF.

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Growth retardation and growth hormone deficiency in patients with Ataxia telangiectasia

Abstract: Our results show that a disturbance in the GH/IGF-1 axis was present in 58.3% of A-T patients. Low levels of GH were the result of reduced central GH secretion. GH treatment may be a therapeutic option for A-T patients with severe growth failure.

Cited by 45 publications

References 43 publications

Endocrine abnormalities in ataxia telangiectasia: findings from a national cohort

Endocrine abnormalities in ataxia telangiectasia: findings from a national cohort

Simple Measurement of IgA Predicts Immunity and Mortality in Ataxia-Telangiectasia

Altered Cerebrospinal Fluid (CSF) in Children with Ataxia Telangiectasia

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