scholarly journals A neglected case of treatable genetic disorder

2016 ◽  
Vol 4 (04) ◽  
pp. 01-03
Author(s):  
C. Rekha ◽  
R. Paramaguru ◽  
Vimala Sarojini ◽  
Dinisha Einstien ◽  
A. Prathiba
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Genetic Disorder ◽  
External Genitalia ◽  
Female Child ◽  
Ambiguous Genitalia ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Adrenal Hormones ◽  
Stage 4 ◽  
21 Hydroxylase Deficiency

Congenital adrenal hyperplasia(CAH) is a autosomal recessive genetic disorder involving adrenal hormones resulting in excessive production of androgens and hence their effects. Here we report a case of CAH which was diagnosed very late but was treated successfully. 12 years old female child came to us with ambiguous genitalia. Examination showed praders stage 4 external genitalia. Evaluated further and confirmed as a case of classic type of simple virilising congenital adrenal hyperplasia due to 21 hydroxylase deficiency. She was successfully treated with steroids and surgical correction was also done. Now child has also attained menarche and on follow up at our pediatric out patient department.

scholarly journals So, and if it is not congenital adrenal hyperplasia? Addressing an undiagnosed case of genital ambiguity

2021 ◽  
Author(s):  
Reinaldo Luna de Omena Filho ◽  
Reginaldo José Petroli ◽  
Fernanda Caroline Soardi ◽  
Débora de Paula Michelatto ◽  
Taís Nitsch Mazzola ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Treatment Options ◽  
External Genitalia ◽  
Autosomal Recessive Disorder ◽  
Missense Variant ◽  
Ambiguous Genitalia ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Genital Ambiguity ◽  
21 Hydroxylase Deficiency

Abstract 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 gene. Researchers-clinicians and researchers-researchers collaborative efforts to elucidate the genetic basis of this disease were critical since this etiologic investigation is not available through the public health system. This case exemplifies the families’ pilgrimage in cases of genital ambiguity due to a rare genetic condition. Recognizing the etiology was the baseline to provide information on prognosis and treatment options, and to shelter family and child doubts and hopes in order to better support their decisions.

Therapeutic challenges in a patient with the simple virilizing (SV) form of congenital adrenal hyperplasia (CAH) due to the P30L/I172N genotype

2019 ◽  
Vol 32 (5) ◽  
pp. 543-547 ◽  
Author(s):  
Maja Tankoska ◽  
Violeta Anastasovska ◽  
Marina Krstevska-Konstantinova ◽  
Michel Naydenov ◽  
Mirjana Kocova
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Polymerase Chain Reaction Amplification ◽  
Point Mutations ◽  
External Genitalia ◽  
High Serum ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Her Family ◽  
Simple Virilizing ◽  
21 Hydroxylase Deficiency

Abstract Background Steroid 21-hydroxylase deficiency is an autosomal recessive disorder, present in 90–95% of all cases with congenital adrenal hyperplasia (CAH). The classical simple virilizing (SV) form of the disease causes virilization of the external genitalia in newborn females and pseudo-precocious puberty in both sexes, due to reactive androgen overproduction. Case presentation We describe a 3.5-year-old girl presenting with pubarche, P2 according to Tanner, advanced bone age of 6 years and 10 months, and high serum levels of 17-hydroxyprogesterone (17-OHP). Molecular analysis of the nine most common pseudogene-derived CYP21A2 point mutations was performed in the patient and her family members using the polymerase chain reaction/amplification-created restriction site (PCR/ACRS) method. We detected the P30L/I172N genotype in the patient. She had inherited a mild P30L mutation from her mother and a severe I172N mutation from her father. Conclusions Although the CAH phenotype is determined by the allele that produces most of the enzyme activity and the mild non-classical (NC) phenotype should be expected, the mild P30L known to be more virilizing probably induced the classical SV phenotype in our patient. A continuous regimen of hydrocortisone at a recommended dose failed to decrease the 17-OHP sufficiently. Careful tapering of the dose did not help, and her pubic hair advanced to P3 according to Tanner. Individually tailored treatment is warranted in this patient.

scholarly journals Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency*

2000 ◽  
Vol 21 (3) ◽  
pp. 245-291 ◽  
Author(s):  
Perrin C. White ◽  
Phyllis W. Speiser
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
External Genitalia ◽  
Clinical Severity ◽  
Sodium Balance ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Gene Encoding ◽  
Salt Wasting ◽  
Direct Mutation ◽  
21 Hydroxylase Deficiency

Abstract More than 90% of cases of congenital adrenal hyperplasia (CAH, the inherited inability to synthesize cortisol) are caused by 21-hydroxylase 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.

scholarly journals Disorders of Sex Development of Adrenal Origin

2021 ◽  
Vol 12 ◽  
Author(s):  
Gabriela P. Finkielstain ◽  
Ana Vieites ◽  
Ignacio Bergadá ◽  
Rodolfo A. Rey
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Disorders Of Sex Development ◽  
External Genitalia ◽  
Special Focus ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Trophic Effect ◽  
Salt Wasting ◽  
Sex Development ◽  
21 Hydroxylase Deficiency

Disorders of Sex Development (DSD) are anomalies occurring in the process of fetal sexual differentiation that result in a discordance between the chromosomal sex and the sex of the gonads and/or the internal and/or external genitalia. Congenital disorders affecting adrenal function may be associated with DSD in both 46,XX and 46,XY individuals, but the pathogenic mechanisms differ. While in 46,XX cases, the adrenal steroidogenic disorder is responsible for the genital anomalies, in 46,XY patients DSD results from the associated testicular dysfunction. Primary adrenal insufficiency, characterized by a reduction in cortisol secretion and overproduction of ACTH, is the rule. In addition, patients may exhibit aldosterone deficiency leading to salt-wasting crises that may be life-threatening. The trophic effect of ACTH provokes congenital adrenal hyperplasia (CAH). Adrenal steroidogenic defects leading to 46,XX DSD are 21-hydroxylase deficiency, by far the most prevalent, and 11β-hydroxylase deficiency. Lipoid Congenital Adrenal Hyperplasia due to StAR defects, and cytochrome P450scc and P450c17 deficiencies cause DSD in 46,XY newborns. Mutations in SF1 may also result in combined adrenal and testicular failure leading to DSD in 46,XY individuals. Finally, impaired activities of 3βHSD2 or POR may lead to DSD in both 46,XX and 46,XY individuals. The pathophysiology, clinical presentation and management of the above-mentioned disorders are critically reviewed, with a special focus on the latest biomarkers and therapeutic development.

scholarly journals Severe Short Stature in an Adolescent Male with Prader-Willi Syndrome and Congenital Adrenal Hyperplasia: A Therapeutic Conundrum

2017 ◽  
Vol 2017 ◽  
pp. 1-4 ◽  
Author(s):  
Meredith Wasserman ◽  
Erin M. Mulvihill ◽  
Angela Ganan-Soto ◽  
Serife Uysal ◽  
Jose Bernardo Quintos
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Short Stature ◽  
Genetic Disorder ◽  
Uniparental Disomy ◽  
Adolescent Male ◽  
Chromosome 15 ◽  
Prader Willi Syndrome ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
21 Hydroxylase Deficiency

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency results in excess androgen production which can lead to early epiphyseal fusion and short stature. Prader-Willi syndrome (PWS) is a genetic disorder resulting from a defect on chromosome 15 due to paternal deletion, maternal uniparental disomy, or imprinting defect. Ninety percent of patients with PWS have short stature. In this article we report a patient with simple-virilizing CAH and PWS who was overtreated with glucocorticoids for CAH and not supplemented with growth hormone for PWS, resulting in a significantly short adult height.

Congenital adrenal hyperplasia

2010 ◽  
pp. 1891-1900
Author(s):  
I.A. Hughes
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Ambiguous Genitalia ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Salt Wasting ◽  
Recessive Mutations ◽  
Adrenal Steroidogenesis ◽  
Life Threatening ◽  
Adrenal Rest ◽  
21 Hydroxylase Deficiency

Congenital adrenal hyperplasia (CAH) results from enzymatic defects in the pathways of adrenal steroidogenesis, with over 90% of cases being due to 21-hydroxylase deficiency caused by autosomal recessive mutations in the CYP21 gene. Classical presentation—this is in the neonatal period with ambiguous genitalia/virilization of a female infant, with phenotype traditionally subdivided according to the presence (75%) or absence of salt wasting, which in affected males is the sole manifestation (and can, if unrecognized, be life-threatening). Delayed presentations can occur, manifest in women as hirsutism, oligomenorrhoea, and infertility and in men as infertility or testicular adrenal rest tumours....

Congenital Adrenal Hyperplasia Presenting with Posterior Labial Fusion Without Clitoromegaly

PEDIATRICS ◽  
1980 ◽  
Vol 66 (2) ◽  
pp. 312-314
Author(s):  
William N. Marshall ◽  
Elmer S. Lightner
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Mexican American ◽  
Linear Growth ◽  
American Woman ◽  
Normal Pregnancy ◽  
Ambiguous Genitalia ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Labial Fusion ◽  
21 Hydroxylase Deficiency

In females with congenital adrenal hyperplasia, 21-hydroxylase deficiency without salt loss is usually recognized in the neonate because of ambiguous genitalia (ie, clitoromegaly with or without labial fusion), or at a later age because of progressive virilization and/or accelerated linear growth. We are reporting the second case of posterior labial fusion without clitoromegaly as the presenting sign of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Here, as in the prior case of Wolff et al,1 the absence of clitoromegaly postponed recognition of the patient's problem. CASE REPORT C.V. was born at term to a 25-year old, gravida 2, para 1, Mexican-American woman after a normal pregnancy; only vitamins were taken during the pregnancy.

Neonatal Salt Loss in the Hypertensive Form of Congenital Adrenal Hyperplasia

PEDIATRICS ◽  
1980 ◽  
Vol 65 (4) ◽  
pp. 777-781
Author(s):  
J. H. Holcombe ◽  
B. S. Keenan ◽  
B. L. Nichols ◽  
R. T. Kirkland ◽  
G. W. Clayton
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Severe Hypertension ◽  
Ambiguous Genitalia ◽  
Elevated Plasma ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Newborn Period ◽  
Dexamethasone Therapy ◽  
21 Hydroxylase Deficiency ◽  
Low Cortisol

The 11β-hydroxylase deficiency (11OHD) form of congenital adrenal hyperplasia is diagnosed infrequently during the newborn period. A child presumed to have the 21-hydroxylase deficiency form of congenital adrenal hyperplasia was studied extensively as an infant. The diagnosis was based on ambiguous genitalia, elevated 17-ketosteroids, evidence of urinary 11-ketopregnanetriol, and salt loss. Severe hypertension was detected at 11 years, and 11β-hydroxylase deficiency was confirmed with elevated plasma 11-deoxycorticosterone and 11-deoxycortisol, low cortisol, and normalization of blood pressure following glucocorticoid replacement. Impaired aldosterone biosynthesis and salt loss were demonstrated during dexamethasone therapy. Salt loss during infancy does not distinguish between the 11β- and 21-hydroxylase deficiency forms of congenital adrenal hyperplasia.

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