Regarding the Consensus Statement on 21-Hydroxylase Deficiency from the Lawson Wilkins Pediatric Endocrine Society and The European Society for Paediatric Endocrinology (original) (raw)
Related papers
2010
More than 90% of cases of congenital adrenal hyperplasia (CAH, the inherited inability to synthesize cortisol) are caused by 21hydroxylase deficiency. Females with severe, classic 21-hydroxylase deficiency are exposed to excess androgens prenatally and are born with virilized external genitalia. Most patients cannot synthesize sufficient aldosterone to maintain sodium balance and may develop potentially fatal "salt wasting" crises if not treated. The disease is caused by mutations in the CYP21 gene encoding the steroid 21-hydroxylase enzyme. More than 90% of these mutations result from intergenic recombinations between CYP21 and the closely linked CYP21P pseudogene. Approximately 20% are gene deletions due to unequal crossing over during meiosis, whereas the remainder are gene conversions-transfers to CYP21 of deleterious mutations normally present in CYP21P. The degree to which each mutation compromises enzymatic activity is strongly correlated with the clinical severity of the disease in patients carrying it. Prenatal diagnosis by direct mutation detection permits prenatal treatment of affected females to minimize genital virilization. Neonatal screening by hormonal methods identifies affected children before salt wasting crises develop, reducing mortality from this condition. Glucocorticoid and mineralocorticoid replacement are the mainstays of treatment, but more rational dosing and additional therapies are being developed. (Endocrine Reviews 21: 2000)
2021
The Congenital Adrenal Hyperplasia due to 21 hydroxylase deficiency is the most common cause of genital ambiguity in persons with XX sexual chromosomes. Genital ambiguity among persons with XY sexual chromosomes comprises diverse and rare etiologies. The deficiency of 17-beta-hydroxysteroid dehydrogenase type 3 enzyme (HSD17B3) is a rare autosomal recessive disorder due to functionally altered variants of the HSD17B3 gene. In this disorder/difference of sex development, the conversion of androstenedione into testosterone is impaired. The appearance of external genitalia of 46,XY individuals varies from typically male to almost female. We report on a child presenting severe ambiguous genitalia. Due to access constraints, specialized care did not start until the child was 10 months old. Parents are consanguineous and were born in an area of high isonymy that is a cluster for rare recessive diseases. A new homozygous missense variant c.785G > T was found in exon 10 of the HSD17B3 ge...
Türk Pediatri Arşivi
Disorders of sex development are defined as conditions in which the chromosomal, gonadal, and anatomic sex is discordant. Patients usually present with atypical appearing genitalia. In the assessment of neonates with disorders of sex development, first, it is important to determine whether this situation requires prompt evaluation, and then the karyotype, hormone levels, and underlying etiology should be determined as soon as possible. All these procedures should be performed in the guidance of a multidisciplinary team in reference centers. As the physical examination of the infant is extremely important, the physcian should suspect and then perform a detailed history and physical examinationi and lastly plan the required laboratory and imaging procedures for the definite diagnosis. It is important not to be hurried in the choice of sex. The aim of this article, which includes the diagnostic and therapeutic approaches in infants with ambiguous genitalia, was to provide a common practice for all pediatricians.
Journal of medical case reports, 2017
Deficiency in 11β-hydroxylase as a cause of congenital adrenal hyperplasia is uncommon. It should be considered in the differential diagnosis of hypertension with virilization in any prepubescent child. A 12-year-old Asian boy from eastern Nepal presented with pain in his abdomen and hypertension. He was raised as a male but had absent testicles since birth and had precocious puberty. Plasma testosterone, follicle-stimulating hormone, and luteinizing hormone were below baseline level. Basal 17-hydroxyprogesterone was elevated. Magnetic resonance imaging of his pelvis showed presence of Müllerian structures and karyotyping revealed 46,XX genotype. A clinical diagnosis of 11β-hydroxylase deficiency was made in view of hypertension with severe virilization in a 46,XX individual. Our patient's legal guardian was unwilling for our patient to change gender and because our patient is underage, the condition was well explained to his parents. He was managed with steroids and antihyperte...
Late Onset Congenital Adrenal Hyperplasia Presenting at Puberty with Ambiguous Genitalia: Surgery with Dexamethasone Resulting in Live New-born Normal Child, 2017
Hirsutism is normally found with raised androgens along with excessive hair in the female giving a male like pattern and rarely in anovulation may a female present with virilization extreme in just simple PCOS. But here we present a girl who presented with late onset congenital hyperplasia who presented at puberty with development of ambiguous genitalia giving the impression of a fall causing it but investigations revealed a normal karyotype &raised 17 hydroxy progesterone with marked stimulation with ACTH and examination under anesthesia revealing a normal female like pattern after which her external genitalia were refashioned and she conceived after getting married on dexamethasone giving birth to an apparently normal daughter.
Congenital Adrenal Hyperplasia in Patients with Disorders of Sexual Differentiation
THE JOURNAL OF MICROBIOLOGY AND MOLECULAR GENETICS
Congenital Adrenal Hyperplasia (CAH) is considered to be the most common cause of genital ambiguity in children. According to World’s literature, 90-95% of this disease is caused by 21-hydroxylase deficiency that impairs the synthesis of cortisol and aldosterone. The consequent excess in androgen production leads to virilization in the affected females. This study was aimed to find the number of cases with CAH (21-hydroxylase deficiency) in the children presented with disorders of sexual differentiation. For this purpose, 100 patients presented to The Children’s hospital for gender assessment were taken and their 17- OH progesterone levels were measured to confirm 21-hydroxylase deficiency, and chromosomal analysis was done to confirm chromosomal sex. Results indicated that out of 100 patients 49 were suffering from CAH. 63.2% of CAH patients were initially presented as males. Out of these, 44.8% were reassigned female gender on chromosomal analysis. So, it is concluded that the maj...
[Causes of ambiguous external genitalia in neonates]
Srpski arhiv za celokupno lekarstvo
The classification of disorders such as ambiguous genitalia in newborns is difficult because similar or identical phenotypes could have several different aetiologies. In most cases it was impossible to correlate the aetiology of the disorder and the appearance of the external genitalia [1-3]. A newborn with ambiguous genitalia needs prompt evaluation that will permit gender assignment and detection of life-threatening conditions (salt-losing crisis due to congenital adrenal hyperplasia or Wilms' tumour). We studied the causes and characteristics of ambiguous genitalia in newborn infants over the period from 1990 to 1999. The following genital phenotypes are considered as ambiguous: 1. Hypospadias with no palpable gonads; 2. Hypospadias with micropenis and no palpable gonads or one palpable gonad; 3. Newborn with female external genitalia and a gonadal mass in labia or labial fusion and/or clitoral enlargement [1, 4]. The diagnostic evaluation of newborns with ambiguous genitalia...
Paediatrica Indonesiana, 2021
Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder commonly caused by mutation of the CYP21A2 gene, resulting in deficiency of an enzyme required for cortisol synthesis in the adrenal cortex. In 90-95% of cases, the deficient enzyme is 21-hydroxylase (21-OH), with an incidence ranging from 1 in 5,000 to 15,000 live births across various ethnic and racial backgrounds. In classical 21-OH deficiency (21-OHD) CAH, excessive androgen exposure in the fetus results in virilization at birth.1 The management of ambiguous genitalia in children with CAH presents a unique and ethically challenging decision-making dilemma for the medical team. Insensitive and poorly informed statements made in the delivery room may cause long-term psychological problems for the families. It is important to refrain from assigning gender until sufficient diagnostic information can be gathered. Parents, as guardians, and the supporting medical team must make decisions on behalf of the child, wi...