"Congenital Adrenal Hypoplasia"

No abstract text is available yet for this article.

No abstract text is available yet for this article.

BACKGROUND: Adrenal Hypoplasia Congenita (AHC) is a rare subtype of primary adrenal insufficiency (PAI) that can go undiagnosed easily. In this article, we report two brothers with hypogonadotropic hypogonadism and novel mutations in the NR0B1 gene who were misdiagnosed and mismanaged as having congenital adrenal hypoplasia (CAH) for several years. CASE PRESENTATION: Herein, we describe two brothers with similar histories; first, they were diagnosed with CAH and treated for that; however, after several years, they showed symptoms of lack of testosterone despite receiving CAH treatment...

Adrenal hypoplasia congenita, attributed to NR0B1 pathogenic variants, accounts for more than 50% of the incidence of primary adrenal insufficiency in children. Although more than 250 different deleterious variations have been described, no genotype-phenotype correlation has been defined to date. We report a case of an adopted boy who reported the onset of an adrenal crisis at 2 weeks of age, requiring replacement therapy with mineralocorticoids and glucocorticoids for 4 months. For 3 years, he did well without treatment...

OBJECTIVES: Congenital X-linked adrenal hypoplasia is a rare disease with a known genetic basis characterized by adrenal insufficiency, hypogonadotropic hypogonadism, and a wide variety of clinical manifestations. CASE PRESENTATION: We present the case of a 26-day old male newborn with symptoms consistent with adrenal insufficiency, hyponatremia, and hyperkalemia. Following NaCl and fludrocortisone supplementation, the patient remained clinically stable. 17-OH-progesterone testing excluded congenital adrenal hyperplasia...

CONTEXT: Primary adrenal insufficiency (PAI) is a life-threatening condition characterized by the inability of the adrenal cortex to produce sufficient steroid hormones. E3 ubiquitin protein ligase zinc and ring finger 3 (ZNRF3) is a negative regulator of Wnt/β-catenin signaling. R-spondin 1 (RSPO1) enhances Wnt/β-catenin signaling via binding and removal of ZNRF3 from the cell surface. OBJECTIVE: This work aimed to explore a novel genetic form of PAI...

In a majority of individuals with disorders/differences of sex development (DSD) a genetic etiology is often elusive. However, new genes causing DSD are routinely reported and using the unbiased genomic approaches, such as whole exome sequencing (WES) should result in an increased diagnostic yield. Here, we performed WES on a large cohort of 125 individuals all of Algerian origin, who presented with a wide range of DSD phenotypes. The study excluded individuals with congenital adrenal hypoplasia (CAH) or chromosomal DSD...

Context: Mutations in the NR0B1 gene, also well-known as the DAX1 gene, are known to cause congenital adrenal hypoplasia associated with hypogonadotropic hypogonadism. The abnormal NR0B1 protein fails to suppress the transcription of promoters of steroidogenic enzymes, which are also targets of NR5A1 protein, also well-known as Ad4BP/SF-1 protein. Since NR5A1 and NR0B1 have antagonistic effects on steroidogenesis, the loss of function due to NR0B1 mutations may be compensated by inducing loss of function of NR5A1 protein...

Congenital adrenal hypoplasia or adrenal hypoplasia congenita (AHC) is a rare disorder ascribed to mutations in three genes, namely, the dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X chromosome, gene 1 (DAX-1/NROB1 gene), steroidogenic factor-1 gene (SF-1/NR5A1 gene), and Achalasia-Addisonianism-Alacrima syndrome gene (AAAS gene). Five cases of AHC of local South Asian origin are described here. Golden Helix VarSeq 2.2.0 (Golden Helix Inc., Bozeman, MT, United States), the clinical genomics interpretation and reporting platform, was used for genetic study...

Background: NR0B1 pathogenic variants can cause congenital adrenal hypoplasia or primary adrenal insufficiency in early childhood usually associated with hypogonadotropic hypogonadism. NR0B1 is necessary for organogenesis of the adrenal cortex and to maintain normal spermatogenesis. In humans, restoration of fertility in patients carrying NR0B1 pathogenic variants is challenging. Objective: The aim of the study was to investigate the clinical, hormonal, histological, spermiological, and molecular genetic characteristics of a cohort of patients with NR0B1 pathogenic variants, monitored for fertility preservation...

X-linked congenital adrenal hypoplasia due to NR0B1 mutation is characterized by hypogonadotropic hypogonadism (HH) and infertility. Here, we describe a novel pathogenic frameshift variant in NR0B1 associated with congenital adrenal hypoplasia by whole exome sequencing in an Iranian case with high level of testosterone. Clinical evaluations and pedigree drawing were performed. Point mutations, gene conversions, and large deletions of the CYP21A2 gene were checked. WES and segregation analyses were conducted...

Complex glycerol kinase deficiency (CGKD) is a rare genetic syndrome which belongs to the group of contiguous gene syndromes and is caused by microdeletion of genes located in Xp21. Patients with CGKD present with features characteristic for adrenal hypoplasia, glycerol kinase deficiency, Duchenne muscular dystrophy and sometimes intellectual disability. We present a long-term follow-up of two unrelated boys with molecular diagnosis of complex glycerol kinase deficiency. Genetic examinations in both patients revealed a deletion on Xp21 chromosome including complete deletion of NR0B1 and GK genes...

BACKGROUND: Contiguous gene deletion syndromes are rare genomic disorders caused by deletion of large segments of DNA resulting in co-occurrence of apparently unrelated multiple clinical phenotypes. We report a boy with contiguous gene deletion involving Xp21 genomic location. CASE PRESENTATION: A Sri Lankan boy with developmental delay and failure to thrive first presented at three years of age with hypovolaemia, hyperpigmentation and drowsiness. Investigations done at that time revealed hypoglycaemia, hyponatraemia, hyperkalaemia, low cortisol, low aldosterone, high ACTH and low 17-hydroxyprogesterone...

BACKGROUND: Most patients with congenital adrenal hypoplasia (AHC) develop symptoms during infantile and juvenile periods, with varying clinical manifestations. AHC is a disease that is easily misdiagnosed as Addison's disease or congenital adrenal hyperplasia (CAH). There was also a significant time difference between the age at which patients developed symptoms and the age at which they were diagnosed with AHC. Most patients showed early symptoms during infantile and juvenile periods, but were diagnosed with AHC many years later...

We report a case of Xp21 deletion syndrome, a contiguous gene syndrome associating glycerol kinase deficiency, Duchenne muscular dystrophy, and congenital adrenal hypoplasia. This results in a contraindication to the use of all halogenated agents and of propofol. We used regional anesthesia combined with dexmedetomidine and ketamine. Previously, the patient had received inadvertently a propofol-based total intravenous anesthesia (TIVA) with no clinical side effects. We were unfortunately unable to document the metabolic consequences of this glycerol load...

BACKGROUND: DAX1 mutations are related to the X-linked form of adrenal hypoplasia congenita (AHC) in infancy and to hypogonadotropic hypogonadism (HH) in puberty. We report a male patient affected by X-linked AHC who presented with central diabetes insipidus and schwannoma in adulthood, which has not been described in association with AHC. CASE PRESENTATION: A 36-day-old male infant who presented with severe dehydration was admitted to the intensive care unit. His laboratory findings showed hyponatremia, hyperkalemia, hypoglycemia, and metabolic acidosis...

X-linked congenital adrenal hypoplasia is characterised by the acute onset of primary adrenal insufficiency in infancy or early childhood and hypogonadotropic hypogonadism (HH) at puberty, arising from mutations of the nuclear receptor subfamily 0 group B member 1 (NR0B1) gene. This study investigated an extended family with two affected males (patient A: 23 years and patient B: 2 months old) and three carrier females. Sequencing analysis of the NR0B1 gene coding region from the family revealed a novel hemizygous deletion [c...

Here we describe the case of a pig with intersex traits including ambiguous external genitalia, sex chromosome abnormalities and a late-onset vanishing testis-like syndrome. It was identified shortly after birth by presenting a predominantly female phenotype with two large scrotal masses resembling testes. The karyotype is 38,XX (53%)/38,XY (47%). Sex steroid levels were undetectable at 1 and 7 months old, whereas circulating cortisol levels were typical. DNA studies excluded gene alterations in sex-determining region Y (SRY), dosage-sensitive sex reversal-congenital adrenal hypoplasia critical region on the X chromosome protein 1 (DAX1), SRY-related high mobility group-box gene 9 (SOX9), nuclear receptor subfamily 5, group a, member 1 (NR5A1), nuclear receptor subfamily 3, group c, member 4 (NR3C4) and steroid 5-alpha-reductase 2 (SRD5A2)...

Inherited bone marrow failure syndromes (IBMFS) are caused by mutations in genes associated with DNA repair and telomere maintenance. In addition, mutations in ribosome-related genes cause defective hematopoiesis. Patients with IBMFS exhibit a predisposition to developing hematological malignancy or solid tumor because of the defect in cellular and molecular hemostasis. The SAMD9 mutation causes the multisystem disorder, MIRAGE syndrome, characterized by congenital adrenal hypoplasia and loss of chromosome 7, providing a novel insight into the correlation between the germline and somatic mutations of SAMD9/SAMD9L and myelodysplastic syndrome (MDS) with monosomy 7...

PURPOSE: To identify the accurate clinical diagnosis of rare syndromic inherited retinal diseases (IRDs) based on the combination of clinical and genetic analyses. METHODS: Four unrelated families with various autosomal recessive syndromic inherited retinal diseases were genetically investigated using whole-exome sequencing (WES). RESULTS: Two affected subjects in family MOL0760 presented with a distinctive combination of short stature, developmental delay, congenital mental retardation, microcephaly, facial dysmorphism and retinitis pigmentosa (RP)...