Clinical and molecular characterization of five Spanish kindreds with X-linked adrenal hypoplasia congenita: atypical findings and a novel mutation in NR0B1
-
Amaia Rodríguez Estévez
,
Juan P. López-Siguero
Abstract
Background: X-linked adrenal hypoplasia congenita (AHC) is caused by NR0B1 (DAX1) gene mutations. Affected male children suffer from adrenal insufficiency, leading to a salt-wasting crisis in early infancy and hypogonadotropic hypogonadism in adulthood.
Objective: To characterize clinically and at the molecular level a cohort of Spanish patients with AHC.
Patients and methods: Nine boys (from five families) with AHC were screened for NR0B1 mutations. Clinical and endocrine evaluations were recorded.
Results: NR0B1 gene mutations were found in all analyzed patients, one of them being novel (p.Gln305*). One patient presented with preserved hypothalamic-pituitary-gonadal axis. Salt-wasting episodes, delayed puberty, and hypogonadotropic hypogonadism were common, although no association was observed between AHC phenotype and genetic mutations. None of the patients has had descendants.
Conclusions: AHC phenotype cannot be predicted based on genetic results as there is no definite genotype-phenotype relationship, including intrafamilial variability. Nevertheless, genetic testing for NR0B1 mutations is indicated if there is a suspicion of an X-linked adrenal insufficiency in order to proceed with the appropriate therapy and genetic counseling.
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©2015 by De Gruyter
Articles in the same Issue
- Frontmatter
- Highlight: Growth hormone
- Growth hormone and growth hormone deficiency – still a lot to learn
- Dynamic changes in the hypothalamic- pituitary-adrenal axis during growth hormone therapy in children with growth hormone deficiency: a multicenter retrospective study
- Pituitary gland size is a useful marker in diagnosing isolated growth hormone deficiency in short children
- Carotid intima-media thickness in children treated with growth hormone
- The c.301_302delAG PROP1 gene mutation in Romanian patients with multiple pituitary hormone deficiency
- Growth impairment and growth hormone-IGF-1 axis in infantile anorexia nervosa
- Growth hormone deficiency in a patient with mitochondrial disease
- Perrault syndrome with growth hormone deficiency: a rare autosomal recessive disorder
- Review articles
- Phosphate homeostasis and genetic mutations of familial hypophosphatemic rickets
- Gonadal malignancy risk and prophylactic gonadectomy in disorders of sexual development
- Original articles
- Carotid intimal medial thickness and its relation to endothelial dysfunction and echocardiographic changes in adolescents with type 1 diabetes
- Insulin dynamics and biochemical markers for predicting impaired glucose tolerance in obese Thai youth
- Effects of adolescence-onset hypogonadism on metabolism, bone mineral density and quality of life in adulthood
- Spectrum of clinical presentations and endocrinological findings of patients with septo-optic dysplasia: a retrospective study
- Role of circulating adipocytokines vaspin, apelin, and visfatin in the loss of appetite in underweight children: a pilot trial
- Protein-induced hyperinsulinaemic hypoglycaemia due to a homozygous HADH mutation in three siblings of a Saudi family
- Waist-to-height ratio as a screening measure for identifying adolescents with hypertriglyceridemic waist phenotype
- Assessment and relation of total and regional fat mass with bone mineral content among Indian urban adolescents
- Evaluation of the relationship between serum adropin levels and blood pressure in obese children
- Swallowed glucocorticoid therapy for eosinophilic esophagitis in children does not suppress adrenal function
- Response of vitamin D binding protein and free vitamin D concentrations to vitamin D supplementation in hospitalized premature infants
- Can school health check-ups serve as screening tool for growth anomalies and obesity in children?
- The spectrum of 46XY disorders of sex development in a University centre in Saudi Arabia
- Clinical and molecular characterization of five Spanish kindreds with X-linked adrenal hypoplasia congenita: atypical findings and a novel mutation in NR0B1
- Clinical characteristics of children referred for signs of early puberty before age 3
- Effects of GnRH analogue treatment on anterior pituitary hormones in children with central precocious puberty
- Anti-Müllerian hormone in children: a ten-year prospective longitudinal study (EarlyBird 39)
- Patient reports
- A rare cause of fatal pulmonary alveolar proteinosis: Niemann-Pick disease type C2 and a novel mutation
- Migratory polyarthritis as an adverse effect of thiamazole use in a 13-year-old girl with Graves’ disease
- Dyshormonogenesis seems to be more frequent in a group of Cameroonian children with congenital hypothyroidism
- Primary systemic carnitine deficiency: a Turkish case with a novel homozygous SLC22A5 mutation and 14 years follow-up
- Cerebral infarction and femoral venous thrombosis detected in a patient with diabetic ketoacidosis and heterozygous factor V Leiden G1691A and PAI-1 4G/5G mutations
- Combined adrenal failure and testicular adrenal rest tumor in a patient with nicotinamide nucleotide transhydrogenase deficiency
- Short communication
- Tamoxifen-associated hirsutism: an unusual side effect in a 5-year-old girl with McCune-Albright syndrome
- Letters to the Editor
- Psychiatric disorders are associated with increased risk for developing hyponatraemia in children
- Rett syndrome and precocious puberty association
Articles in the same Issue
- Frontmatter
- Highlight: Growth hormone
- Growth hormone and growth hormone deficiency – still a lot to learn
- Dynamic changes in the hypothalamic- pituitary-adrenal axis during growth hormone therapy in children with growth hormone deficiency: a multicenter retrospective study
- Pituitary gland size is a useful marker in diagnosing isolated growth hormone deficiency in short children
- Carotid intima-media thickness in children treated with growth hormone
- The c.301_302delAG PROP1 gene mutation in Romanian patients with multiple pituitary hormone deficiency
- Growth impairment and growth hormone-IGF-1 axis in infantile anorexia nervosa
- Growth hormone deficiency in a patient with mitochondrial disease
- Perrault syndrome with growth hormone deficiency: a rare autosomal recessive disorder
- Review articles
- Phosphate homeostasis and genetic mutations of familial hypophosphatemic rickets
- Gonadal malignancy risk and prophylactic gonadectomy in disorders of sexual development
- Original articles
- Carotid intimal medial thickness and its relation to endothelial dysfunction and echocardiographic changes in adolescents with type 1 diabetes
- Insulin dynamics and biochemical markers for predicting impaired glucose tolerance in obese Thai youth
- Effects of adolescence-onset hypogonadism on metabolism, bone mineral density and quality of life in adulthood
- Spectrum of clinical presentations and endocrinological findings of patients with septo-optic dysplasia: a retrospective study
- Role of circulating adipocytokines vaspin, apelin, and visfatin in the loss of appetite in underweight children: a pilot trial
- Protein-induced hyperinsulinaemic hypoglycaemia due to a homozygous HADH mutation in three siblings of a Saudi family
- Waist-to-height ratio as a screening measure for identifying adolescents with hypertriglyceridemic waist phenotype
- Assessment and relation of total and regional fat mass with bone mineral content among Indian urban adolescents
- Evaluation of the relationship between serum adropin levels and blood pressure in obese children
- Swallowed glucocorticoid therapy for eosinophilic esophagitis in children does not suppress adrenal function
- Response of vitamin D binding protein and free vitamin D concentrations to vitamin D supplementation in hospitalized premature infants
- Can school health check-ups serve as screening tool for growth anomalies and obesity in children?
- The spectrum of 46XY disorders of sex development in a University centre in Saudi Arabia
- Clinical and molecular characterization of five Spanish kindreds with X-linked adrenal hypoplasia congenita: atypical findings and a novel mutation in NR0B1
- Clinical characteristics of children referred for signs of early puberty before age 3
- Effects of GnRH analogue treatment on anterior pituitary hormones in children with central precocious puberty
- Anti-Müllerian hormone in children: a ten-year prospective longitudinal study (EarlyBird 39)
- Patient reports
- A rare cause of fatal pulmonary alveolar proteinosis: Niemann-Pick disease type C2 and a novel mutation
- Migratory polyarthritis as an adverse effect of thiamazole use in a 13-year-old girl with Graves’ disease
- Dyshormonogenesis seems to be more frequent in a group of Cameroonian children with congenital hypothyroidism
- Primary systemic carnitine deficiency: a Turkish case with a novel homozygous SLC22A5 mutation and 14 years follow-up
- Cerebral infarction and femoral venous thrombosis detected in a patient with diabetic ketoacidosis and heterozygous factor V Leiden G1691A and PAI-1 4G/5G mutations
- Combined adrenal failure and testicular adrenal rest tumor in a patient with nicotinamide nucleotide transhydrogenase deficiency
- Short communication
- Tamoxifen-associated hirsutism: an unusual side effect in a 5-year-old girl with McCune-Albright syndrome
- Letters to the Editor
- Psychiatric disorders are associated with increased risk for developing hyponatraemia in children
- Rett syndrome and precocious puberty association
