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Bone mineral density, bone markers, and fractures in adult males with congenital adrenal hyperplasia.

https://arctichealth.org/en/permalink/ahliterature118415
Source
Eur J Endocrinol. 2013 Mar;168(3):331-41
Publication Type
Article
Date
Mar-2013
Author
Henrik Falhammar
Helena Filipsson Nyström
Anna Wedell
Kerstin Brismar
Marja Thorén
Author Affiliation
Department of Endocrinology, Metabolism and Diabetes, D02:04, Karolinska University Hospital, SE-171 76 Stockholm, Sweden. henrik.falhammar@ki.se
Source
Eur J Endocrinol. 2013 Mar;168(3):331-41
Date
Mar-2013
Language
English
Publication Type
Article
Keywords
Adrenal Hyperplasia, Congenital - drug therapy - genetics - metabolism - physiopathology
Adult
Aged
Biological Markers - blood
Bone Density
Bone and Bones - metabolism
Cohort Studies
Fractures, Bone - epidemiology - etiology
Genetic Association Studies
Glucocorticoids - adverse effects - therapeutic use
Hormone Replacement Therapy - adverse effects
Humans
Insulin-Like Growth Factor I - analysis
Male
Middle Aged
Mutation
Osteocalcin - blood
Osteoporosis - epidemiology - etiology - physiopathology
Prevalence
Steroid 21-Hydroxylase - genetics - metabolism
Sweden - epidemiology
Young Adult
Abstract
The aim of this study was to determine bone mineral density (BMD), markers of bone metabolism, fractures, and steroids reflecting hormonal control in adult males with congenital adrenal hyperplasia (CAH). SUBJECTS, METHODS, AND DESIGN: We compared CAH males with 21-hydroxylase deficiency (n=30), 19-67 years old, with age- and sex-matched controls (n=32). Subgroups of CYP21A2 genotypes, age, glucocorticoid preparation, poor control vs overtreatment, and early vs late (>36 months) diagnosis were studied. BMD measured by dual energy X-ray absorptiometry and markers of bone metabolism and androgens/17-hydroxyprogesterone levels were investigated.
All, including older (>30 years), CAH patients had lower BMD in all measured sites compared with control subjects. The null group demonstrated lower BMD in more locations than the other groups. Osteoporosis/osteopenia was present in 81% of CAH patients compared with 32% in controls (=30 years). Fracture frequency was similar, osteocalcin was lower, and fewer patients than controls had vitamin D insufficiency. IGF1 was elevated in the milder genotypes. In patients, total body BMD was positively correlated to weight, BMI, total lean body mass, and triglycerides, and negatively to prolactin. Patients on prednisolone had lower BMD and osteocalcin levels than those on hydrocortisone/cortisone acetate. Patients with poor control had higher femoral neck BMD. There were no differences in BMD between patients with an early vs late diagnosis.
CAH males have low BMD and bone formation markers. BMD should be monitored, adequate prophylaxis and treatment established, and glucocorticoid doses optimized to minimize the risk of future fractures.
PubMed ID
23211577 View in PubMed
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Heterogeneity of disease-causing variants in the Swedish galactosemia population: Identification of 16 novel GALT variants.

https://arctichealth.org/en/permalink/ahliterature310439
Source
J Inherit Metab Dis. 2019 09; 42(5):1008-1018
Publication Type
Journal Article
Research Support, Non-U.S. Gov't
Date
09-2019
Author
Annika Ohlsson
Mary Hunt
Anna Wedell
Ulrika von Döbeln
Author Affiliation
Centre for Inherited Metabolic Diseases (CMMS), Karolinska University Hospital, Stockholm, Sweden.
Source
J Inherit Metab Dis. 2019 09; 42(5):1008-1018
Date
09-2019
Language
English
Publication Type
Journal Article
Research Support, Non-U.S. Gov't
Keywords
Female
Galactosemias - diagnosis - genetics
Gene Frequency
Genetic Heterogeneity
Humans
Infant, Newborn
Male
Mutation
Neonatal Screening
Sweden
UTP-Hexose-1-Phosphate Uridylyltransferase - genetics
Abstract
The aim was to determine disease-causing variants in the GALT gene which codes for the enzyme galactose-1-phosphate uridylyltransferase. Loss of activity of this enzyme causes classical galactosemia-a life threatening, treatable disorder, included in the Swedish newborn screening program since 1967. A total of 66 patients with the disease are known in Sweden and 56 index patients were investigated. An additional two patients with Duarte galactosemia were included. The disease-causing variants were identified in all patients. As reported from other countries only a few variants frequently recur in severe disease. The two variants p.(Gln188Arg) (c.563A>G) and p.(Met142Lys) (c.425T>A) are present in several index patients whereas the remaining are found in one to three patients each. The most common variant, p.(Gln188Arg), has an allele frequency of 51% in the cohort. A total of 16 novel variants were found among the 33 different variants in the cohort. Two of these are synonymous variants affecting splicing, demonstrating the importance of the evaluation of synonymous variants at the cDNA level. Concise sentence: Galactosemia is a rare disease in Sweden and the disease-causing variants are heterogenous including two synonymous variants.
PubMed ID
31194895 View in PubMed
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Multiplex ligation-dependent probe amplification analysis of the NR0B1(DAX1) locus enables explanation of phenotypic differences in patients with X-linked congenital adrenal hypoplasia.

https://arctichealth.org/en/permalink/ahliterature125752
Source
Horm Res Paediatr. 2012;77(2):100-7
Publication Type
Article
Date
2012
Author
Michela Barbaro
Susanne Bens
Andrea Haake
Michael Peter
Jürgen Brämswig
Paul-Martin Holterhus
Juan Pedro Lopez-Siguero
Udo Menken
Monika Mix
Wolfgang G Sippell
Anna Wedell
Felix G Riepe
Author Affiliation
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. Michela.barbaro@ki.se
Source
Horm Res Paediatr. 2012;77(2):100-7
Date
2012
Language
English
Publication Type
Article
Keywords
Adolescent
Adrenal Hyperplasia, Congenital - genetics - metabolism - physiopathology
Adult
Child
DAX-1 Orphan Nuclear Receptor - genetics - metabolism
Female
Gene Deletion
Genetic Association Studies
Genetic Diseases, X-Linked - genetics - metabolism - physiopathology
Genetic Loci
Heterozygote Detection - methods
Humans
Infant
Interleukin-1 Receptor Accessory Protein - genetics - metabolism
Male
Mental Retardation, X-Linked - genetics
Mothers
Multiplex Polymerase Chain Reaction
Nucleic Acid Amplification Techniques
Oligonucleotide Array Sequence Analysis
Sweden
Abstract
X-linked adrenal hypoplasia congenita (AHC) is a rare disorder characterized by primary adrenal insufficiency and hypogonadic hypogonadism. It is caused by deletions or point mutations of the NR0B1 gene, on Xp21. AHC can be associated with glycerol kinase deficiency, Duchenne muscular dystrophy and mental retardation (MR), as part of a contiguous gene deletion syndrome. A synthetic probe set for multiplex ligation-dependent probe amplification analysis was developed to confirm and characterize NR0B1 deletions in patients with AHC and to correlate their genotypes with their divergent phenotypes.
In 2 patients, isolated AHC was confirmed, while a patient at risk for metabolic crisis was revealed as the deletion extends to the GK gene. A deletion extending to IL1RAPL1 was confirmed in both patients showing MR. Thus, a good genotype-phenotype correlation was confirmed.
Multiplex ligation-dependent probe amplification analysis is a valuable tool to detect NR0B1 and contiguous gene deletions in patients with AHC. It is especially helpful for IL1RAPL1 deletion detection as no clinical markers for MR are available. Furthermore, multiplex ligation-dependent probe amplification has the advantage to identify female carriers that, depending on the deletion extension, have a high risk of giving birth to children with MR, AHC, glycerol kinase deficiency and Duchenne muscular dystrophy.
PubMed ID
22456342 View in PubMed
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Nationwide neonatal screening for congenital adrenal hyperplasia in sweden: a 26-year longitudinal prospective population-based study.

https://arctichealth.org/en/permalink/ahliterature104508
Source
JAMA Pediatr. 2014 Jun;168(6):567-74
Publication Type
Article
Date
Jun-2014
Author
Sebastian Gidlöf
Anna Wedell
Claes Guthenberg
Ulrika von Döbeln
Anna Nordenström
Author Affiliation
Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden2Department of Obstetrics and Gynecology, Karolinska University Hospital, Stockholm, Sweden.
Source
JAMA Pediatr. 2014 Jun;168(6):567-74
Date
Jun-2014
Language
English
Publication Type
Article
Keywords
Adrenal Hyperplasia, Congenital - diagnosis - epidemiology - genetics
Female
Genotype
Humans
Infant
Infant, Newborn
Infant, Premature
Longitudinal Studies
Male
Neonatal Screening - methods
Prospective Studies
Sensitivity and specificity
Steroid 21-Hydroxylase - genetics
Sweden
Abstract
Recent reports have questioned the rationale for neonatal screening for congenital adrenal hyperplasia (CAH) owing to low sensitivity in salt-wasting forms and a high rate of recall (ie, a positive finding resulting in a visit to a pediatrician and a second test) in preterm infants.
To determine the efficiency of the neonatal screening program for CAH in Sweden over time.
Longitudinal prospective population-based study in Sweden. We assessed neonatal screening for CAH from January 1, 1986, through December 31, 2011, when 2?737?932 infants (99.8%) underwent testing. The CYP21A2 genotype was investigated in 219 cases with true-positive findings (94.8%). We investigated the screening outcomes for 231 patients who had true-positive findings, 43 with late diagnosis, and 1497 infants with false-positive findings.
Sensitivity of the screening for salt-wasting CAH. The most important secondary outcome measures were the positive predictive values and recall rates for full-term and preterm infants and sensitivity for milder forms of CAH.
A total of 143 patients with salt-wasting CAH were identified; none were missed. The sensitivity was lower for milder forms of the disorder (P?=?.04), including 79.7% for simple virilizing forms and 32.4% for nonclassic forms. The positive predictive value was higher in full-term (25.1%) than preterm (1.4%) infants and correlated with gestational age (r?=?0.98; P?
Notes
Comment In: JAMA Pediatr. 2014 Jun;168(6):515-624733500
PubMed ID
24733564 View in PubMed
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One hundred years of congenital adrenal hyperplasia in Sweden: a retrospective, population-based cohort study.

https://arctichealth.org/en/permalink/ahliterature258944
Source
Lancet Diabetes Endocrinol. 2013 Sep;1(1):35-42
Publication Type
Article
Date
Sep-2013
Author
Sebastian Gidlöf
Henrik Falhammar
Astrid Thilén
Ulrika von Döbeln
Martin Ritzén
Anna Wedell
Anna Nordenström
Source
Lancet Diabetes Endocrinol. 2013 Sep;1(1):35-42
Date
Sep-2013
Language
English
Publication Type
Article
Keywords
Adolescent
Adrenal Hyperplasia, Congenital - epidemiology - genetics
Adult
Aged
Aged, 80 and over
Child
Child, Preschool
Cohort Studies
Female
Humans
Male
Middle Aged
Population Surveillance - methods
Retrospective Studies
Steroid 21-Hydroxylase - genetics
Sweden - epidemiology
Time Factors
Young Adult
Abstract
Congenital adrenal hyperplasia due to 21-hydroxylase deficiency results in cortisol and aldosterone deficiency and is, in its most severe form, lethal. We aimed to assess the effect of historical medical improvements in the care of patients with this disorder over time and to assess the effects of neonatal screening in Sweden.
For this retrospective, population-based cohort study, we collected data for all known patients with congenital adrenal hyperplasia in Sweden between 1910 and 2011 [corrected]. Data sources included the registry at the Swedish national screening laboratory, patients identified via the Swedish neonatal screening programme, late-diagnosed patients reported to the laboratory, and patients who underwent genetic diagnostics or became known to us through clinical contacts. All known patients were included in a population-based cohort study of the distribution of clinical severity, genotype, sex, and the effect of nationwide neonatal screening.
We identified 606 patients with the disorder, born between 1915 and 2011. The CYP21A2 genotype (conferring deficiency of 21-hydroxylase) was known in 490 patients (81%). The female-to-male ratio was 1·25 in the whole cohort, but close to 1 in patients detected by the screening. We noted a sharp increase in the number of patients diagnosed in the 1960s and 1970s, and after the introduction of neonatal screening in 1986 the proportion of patients with the salt-wasting form of congenital adrenal hyperplasia increased in both sexes, from 114 (47%) of 242 individuals between 1950 and 1985 to 165 (57%) of 292 individuals between 1986 and 2011 (p=0·038). On average, five to ten children were missed every year before 1970. The non-classic form of the disorder was diagnosed more often in women than in men, which accounts for the female preponderance in our cohort.
Our findings suggest that, contrary to current belief, boys and girls with salt-wasting congenital adrenal hyperplasia were equally missed clinically. Neonatal screening improved detection of the salt-wasting form in girls as well as boys, saving lives in both sexes. The non-classic form was diagnosed more often in women than it was in men, leading to the female preponderance in this cohort.
The Swedish Research Council, the Centre of Gender Medicine at Karolinska Institutet, the Stockholm County Council, the Sällskapet Barnavård Foundation, the Stiftelsen Samariten Foundation, the Stiftelsen Frimurare Barnhuset Foundation, and the Novo Nordisk Foundation.
Notes
Comment In: Lancet Diabetes Endocrinol. 2013 Sep;1(1):4-524622253
Erratum In: Lancet Diabetes Endocrinol. 2013 Aug;1 Suppl 1:s22
PubMed ID
24622265 View in PubMed
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Prenatal dexamethasone treatment of children at risk for congenital adrenal hyperplasia: the Swedish experience and standpoint.

https://arctichealth.org/en/permalink/ahliterature125627
Source
J Clin Endocrinol Metab. 2012 Jun;97(6):1881-3
Publication Type
Article
Date
Jun-2012

Prenatal treatment of congenital adrenal hyperplasia.

https://arctichealth.org/en/permalink/ahliterature30023
Source
Eur J Endocrinol. 2004 Nov;151 Suppl 3:U63-9
Publication Type
Article
Date
Nov-2004
Author
Svetlana Lajic
Anna Nordenström
E Martin Ritzén
Anna Wedell
Author Affiliation
Department of Molecular Medicine, Karolinska Institutet, S-17176 Stockholm, Sweden.
Source
Eur J Endocrinol. 2004 Nov;151 Suppl 3:U63-9
Date
Nov-2004
Language
English
Publication Type
Article
Keywords
Adrenal Hyperplasia, Congenital - drug therapy
Clinical Trials
Dexamethasone - administration & dosage - adverse effects - therapeutic use
Female
Follow-Up Studies
Humans
Maternal-Fetal Exchange
Pregnancy
Virilism - prevention & control
Abstract
In foetuses at risk of virilising congenital adrenal hyperplasia (CAH), prenatal treatment can be offered by administration of dexamethasone (DEX) via the mother, in order to suppress foetal adrenal androgen oversecretion and prevent genital malformations. The first treated cases were described 20 years ago, and several hundred pregnancies have been reported since. There is a consensus that the treatment effectively prevents or reduces virilisation, but opinions regarding its safety differ. Rare adverse events have been reported in treated children, but no harmful effect has been documented that can be clearly attributed to the treatment. However, few treated foetuses have been followed until adolescence. Animal studies and epidemiological data point to various adverse effects of excess glucocorticoids on the developing foetus. In order to prevent virilisation effectively in females affected with CAH, the prenatal treatment needs to be instituted in the early first trimester, before prenatal diagnosis is possible. Thus, a majority of treated foetuses will receive DEX unnecessarily.The PREDEX study was initiated in Stockholm in 1999 as an open, controlled, non-randomised, multicentre trial. Participating centres are Stockholm, Bergen, Kuopio, Warsaw, London, Lyon and Barcelona. The study has been approved by the ethics committees in each country. The purpose of PREDEX is to evaluate prospectively the prenatal treatment regarding efficacy in preventing virilisation as well as to study its safety for both mothers and treated children. Children are followed until 18 years of age and a wide range of physiological, metabolic and developmental parameters are considered. In Sweden, treatment is not offered outside the frames of the trial.
PubMed ID
15554888 View in PubMed
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7 records – page 1 of 1.