X-linked adrenal hypoplasia congenita
Specialty	Endocrinology

X-linked adrenal hypoplasia congenita is a genetic disorder^[1] that mainly affects males. It involves many endocrine tissues in the body, especially the adrenal glands.

Presentation

One of the main characteristics of this disorder is adrenal insufficiency, which is a reduction in adrenal gland function resulting from incomplete development of the gland's outer layer (the adrenal cortex). Adrenal insufficiency typically begins in infancy or in childhood and can cause vomiting, difficulty with feeding, dehydration, extremely low blood sugar (hypoglycemia), low sodium levels, and shock. However, adult-onset cases have also been described.^[2] See also Addison's disease.

Affected males may also lack male sex hormones, which leads to underdeveloped reproductive tissues, undescended testicles (cryptorchidism), delayed puberty, and an inability to father children (infertility). These characteristics are known as hypogonadotropic hypogonadism. Females are rarely affected by this disorder, but a few cases have been reported of adrenal insufficiency or a lack of female sex hormones, resulting in underdeveloped reproductive tissues, delayed puberty, and an absence of menstruation.

Genetics

Mutations in the NR0B1 gene located on the X chromosome (Xp21.3-p21.2) cause X-linked adrenal hypoplasia congenita. The NR0B1 gene provides instructions to make a transcription factor protein called DAX1 that helps control the activity of certain genes. When the NR0B1 gene is deleted or mutated, the activity of certain genes is not properly controlled. This leads to problems with the development of the adrenal glands, two structures in the brain (the hypothalamus and pituitary gland), and reproductive tissues (the ovaries or testes). These tissues are important for the production of many hormones that control various functions in the body. When these hormones are not present in the correct amounts, the signs and symptoms of adrenal insufficiency and hypogonadotropic hypogonadism can result. This condition is inherited in an X-linked recessive pattern.

Diagnosis

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Management

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References

External links

Classification

X-linked disorders

X-linked recessive
Immune	Chronic granulomatous disease (CYBB) Wiskott–Aldrich syndrome X-linked severe combined immunodeficiency X-linked agammaglobulinemia Hyper-IgM syndrome type 1 IPEX X-linked lymphoproliferative disease Properdin deficiency
Hematologic	Haemophilia A Haemophilia B X-linked sideroblastic anemia
Endocrine	Androgen insensitivity syndrome/Spinal and bulbar muscular atrophy KAL1 Kallmann syndrome X-linked adrenal hypoplasia congenita
Metabolic	Amino acid: Ornithine transcarbamylase deficiency Oculocerebrorenal syndrome Dyslipidemia: Adrenoleukodystrophy Carbohydrate metabolism: Glucose-6-phosphate dehydrogenase deficiency Pyruvate dehydrogenase deficiency Danon disease/glycogen storage disease Type IIb Lipid storage disorder: Fabry disease Mucopolysaccharidosis: Hunter syndrome Purine–pyrimidine metabolism: Lesch–Nyhan syndrome Mineral: Menkes disease/Occipital horn syndrome
Nervous system	X-linked intellectual disability: Coffin–Lowry syndrome MASA syndrome Alpha-thalassemia mental retardation syndrome PHF8 Eye disorders: Color blindness (red and green, but not blue) Ocular albinism (1) Norrie disease Choroideremia Other: Charcot–Marie–Tooth disease (CMTX2-3) Pelizaeus–Merzbacher disease SMAX2
Skin and related tissue	Dyskeratosis congenita Hypohidrotic ectodermal dysplasia (EDA) X-linked ichthyosis X-linked endothelial corneal dystrophy
Neuromuscular	Becker muscular dystrophy/Duchenne Centronuclear myopathy (MTM1) Conradi–Hünermann syndrome Emery–Dreifuss muscular dystrophy 1
Urologic	Alport syndrome Dent's disease X-linked nephrogenic diabetes insipidus
Bone/tooth	AMELX Amelogenesis imperfecta
No primary system	Barth syndrome McLeod syndrome Smith–Fineman–Myers syndrome Simpson–Golabi–Behmel syndrome Mohr–Tranebjærg syndrome Nasodigitoacoustic syndrome

X-linked dominant
X-linked hypophosphatemia Focal dermal hypoplasia Fragile X syndrome Aicardi syndrome Incontinentia pigmenti Rett syndrome CHILD syndrome Lujan–Fryns syndrome Orofaciodigital syndrome 1 Craniofrontonasal dysplasia

Genetic disorders relating to deficiencies of transcription factor or coregulators

(1) Basic domains

1.2	Feingold syndrome Saethre–Chotzen syndrome
1.3	Tietz syndrome

(2) Zinc finger
DNA-binding domains

2.1	(Intracellular receptor): Thyroid hormone resistance Androgen insensitivity syndrome PAIS MAIS CAIS Kennedy's disease PHA1AD pseudohypoaldosteronism Estrogen insensitivity syndrome X-linked adrenal hypoplasia congenita MODY 1 Familial partial lipodystrophy 3 SF1 XY gonadal dysgenesis
2.2	Barakat syndrome Tricho–rhino–phalangeal syndrome
2.3	Greig cephalopolysyndactyly syndrome/Pallister–Hall syndrome Denys–Drash syndrome Duane-radial ray syndrome MODY 7 MRX 89 Townes–Brocks syndrome Acrocallosal syndrome Myotonic dystrophy 2
2.5	Autoimmune polyendocrine syndrome type 1

(3) Helix-turn-helix domains

3.1	ARX Ohtahara syndrome Lissencephaly X2 MNX1 Currarino syndrome HOXD13 SPD1 synpolydactyly PDX1 MODY 4 LMX1B Nail–patella syndrome MSX1 Tooth and nail syndrome OFC5 PITX2 Axenfeld syndrome 1 POU4F3 DFNA15 POU3F4 DFNX2 ZEB1 Posterior polymorphous corneal dystrophy Fuchs' dystrophy 3 ZEB2 Mowat–Wilson syndrome
3.2	PAX2 Papillorenal syndrome PAX3 Waardenburg syndrome 1&3 PAX4 MODY 9 PAX6 Gillespie syndrome Coloboma of optic nerve PAX8 Congenital hypothyroidism 2 PAX9 STHAG3
3.3	FOXC1 Axenfeld syndrome 3 Iridogoniodysgenesis, dominant type FOXC2 Lymphedema–distichiasis syndrome FOXE1 Bamforth–Lazarus syndrome FOXE3 Anterior segment mesenchymal dysgenesis FOXF1 ACD/MPV FOXI1 Enlarged vestibular aqueduct FOXL2 Premature ovarian failure 3 FOXP3 IPEX
3.5	IRF6 Van der Woude syndrome Popliteal pterygium syndrome

(4) β-Scaffold factors
with minor groove contacts

4.2	Hyperimmunoglobulin E syndrome
4.3	Holt–Oram syndrome Li–Fraumeni syndrome Ulnar–mammary syndrome
4.7	Campomelic dysplasia MODY 3 MODY 5 SF1 SRY XY gonadal dysgenesis Premature ovarian failure 7 SOX10 Waardenburg syndrome 4c Yemenite deaf-blind hypopigmentation syndrome
4.11	Cleidocranial dysostosis

(0) Other transcription factors

0.6	Kabuki syndrome

Ungrouped

Transcription coregulators

Coactivator:	CREBBP Rubinstein–Taybi syndrome
Corepressor:	HR (Atrichia with papular lesions)