Beta-hydroxysteroid Dehydrogenase Deficiency Research Articles

Novel Mutation Among Two Sisters With 17β Hydroxysteroid Dehydrogenase Type 3 Deficiency

The clinical presentations of 17β hydroxysteroid dehydrogenase type 3 (17β-HSD3) deficiency, 5α-reductase type 2 deficiency, and complete androgen insensitivity syndrome can be similar. However, those with 17β-HSD3 deficiency and 5α-reductase type 2 deficiency will develop virilization and should undergo gonadectomy after genetic testing before the age of puberty if reared in the female sex. Two sisters were initially diagnosed with complete androgen insensitivity syndrome as young children after testes were discovered during hernia surgery. Virilization occurred in both sisters during puberty, and a diagnosis of 17β-HSD3 deficiency was suspected. Confirmatory diagnosis through gene sequencing identified a heterozygous mutation for both a known splicing mutation and a previously unreported amplification mutation of the HSD17B3 gene.

Advice on the Management of Ambiguous Genitalia to a Young Endocrinologist from Experienced Clinicians

The birth of a child with ambiguous genitalia is a challenging and distressing event for the family and physician and one with life-long consequences. Most disorders of sexual differentiation (DSD) associated with ambiguous genitalia are the result either of inappropriate virilization of girls or incomplete virilization of boys. It is important to establish a diagnosis as soon as possible, for psychological, social, and medical reasons, particularly for recognizing accompanying life-threatening disorders such as the salt-losing form of congenital adrenal hyperplasia. In most instances, there is sufficient follow-up data so that making the diagnosis also establishes the appropriate gender assignment (infants with congenital adrenal hyperplasia, those with androgen resistance syndromes), but some causes of DSD such as steroid 5α-reductase 2 deficiency and 17β-hydroxysteroid dehydrogenase deficiency are associated with frequent change in social sex later in life. In these instances, guidelines for sex assignment are less well established.

Mutation of 3β-hydroxysteroid dehydrogenase (3β-HSD) at the 3′-untranslated region is associated with adrenocortical insufficiency

In the present study, we report the mutation of the 3β-hydroxysteroid dehydrogenase (3β-HSD) gene in a family suffering from adrenocortical insufficiency. The index patient was clinically diagnosed with adrenocortical insufficiency. Peripheral venous blood (5 ml) was collected from the proband and 5 members of his family, and genomic DNA was extracted. Exons 1, 2, 3 and 4 of the 3β-HSD gene and their flanking sequences were amplified by polymerase chain reaction (PCR). Some of the family members were examined by amplifying only exon 4. The PCR products were then purified and sequenced. The C to T homozygous mutation at nucleotide 1088 and C to G homozygous mutation at nucleotide 1132 within exon 4 of the 3β-HSD gene were found in the family members with abnormal phenotype. In the family members with normal phenotype, heterozygous mutations at the sites mentioned above were identified in the parents and Aunt 1, but not in Aunt 2 of the proband. In conclusion, a family with 3β-HSD deficiency was identified in the present study. The cause of the disease in the studied family appears to be two novel homozygous mutations in the 3β-HSD gene.

In silico structural, functional and pathogenicity evaluation of a novel mutation: An overview of HSD3B2 gene mutations

Mutations of 3 beta hydroxysteroid dehydrogenase type II (HSD3B2) gene result in different clinical consequences. We explain a patient who demonstrated a salt wasting form of 3βHSD deficiency in infancy. Signs of hyponatremia and hyperkalemia were recognized in the infant with ambiguous genitalia and perineal hypospadias. The 46,XY male was genotyped by direct sequencing of HSD3B2 gene. Steroid profiles showed elevated concentration of 17 hydroxyprogesterone, and decrease in concentration of cortisol, and testosterone. Dehydroepiandrotone (DHEA) to androstenedione ratio had 6 fold increases. Direct sequencing of the patient revealed homozygous missense A82P mutation in exon 3. This mutation was confirmed by segregation analysis of the parents. Bioinformatic tools were used for in silico structural and functional analyses. Also, the pathological effect of the mutation was validated by different software. Alanine is a conserved amino acid in the membrane binding domain of the enzyme and proline substitution was predicted to destabilize the protein. This report may highlight the importance of the screening programs of the disorder in Iran.

Homozygosity mapping identifies a bile acid biosynthetic defect in an adult with cirrhosis of unknown etiology

The most common inborn error of bile acid metabolism is 3β-hydroxy-Δ(5)-C(27)-steroid oxidoreductase (3β-HSD) deficiency, a disorder that usually presents in early childhood with hepatic dysfunction. Timely diagnosis of this disorder is crucial because it can be effectively treated with primary bile acid replacement. Here we describe a 24-year-old woman from Iran with cirrhosis of unknown etiology. Her sister and a first cousin died of cirrhosis (ages 19 and 6 years) and another 32-year-old first cousin had a self-limited liver disorder in childhood that resolved at age 9 years. The family history suggested that the affected family members were homozygous for a mutant allele inherited identical-by-descent. A genome-wide analysis of 2.4 million single nucleotide polymorphisms was performed to identify regions of homozygosity that were present in the proband and the 32-year-old first cousin, but not in a healthy relative. One of these regions contained the gene encoding 3β-HSD (HSD3B7). Sequence analysis of HSD3B7 revealed that the proband and her 32-year-old cousin were homozygous for a frameshift mutation (c.45_46del AG, p.T15Tfsx27) in exon 1. The diagnosis of 3β-HSD deficiency was confirmed by documenting high levels of 3β-hydroxy-Δ(5) bile acids in the serum of the proband and the 32-year-old first cousin using mass spectrometry. To our knowledge, the 32-year-old relative in this family represents the oldest asymptomatic patient with this disorder. This study highlights the clinical utility of homozygosity mapping in diagnosing autosomal recessive metabolic disorders. This family illustrates the wide variation in expressivity that occurs in 3β-HSD deficiency and underscores the need to consider a bile acid synthetic defect as a possible cause of liver disease in adults.

Undetectable Levels of CSF Amyloid-β Peptide in a Patient with 17β-Hydroxysteroid Dehydrogenase Deficiency

17β-hydroxysteroid dehydrogenase 10 (HSD10) deficiency is a rare X-linked inborn error of isoleucine catabolism. Although this protein has been genetically implicated in Alzheimer's disease pathogenesis, studies of amyloid-β peptide (Aβ) in patients with HSD10 deficiency have not been previously reported. We found, in a severely affected child with HSD10 deficiency, undetectable levels of Aβ in the cerebrospinal fluid, together with low expression of brain-derived neurotrophic factor, α-synuclein, and serotonin metabolites. Confirmation of these findings in other patients would help elucidating mechanisms of synaptic dysfunction in this disease, and highlight the role of Aβ in both early and late periods of life.

Non-classic congenital adrenal hyperplasia. Clinical experience versus clinical guidelines

The ability to diagnose non-classic congenital adrenal hyperplasia (NC-CAH) has improved drastically over the past decade due to standardization of laboratory assays and refinement of molecular studies. However, the optimal clinical management for this patient population is still evolving. Thus, we describe the clinical presentation and diagnostic approach of children with non-classic congenital adrenal hyperplasia (NC-CAH). A retrospective chart review was done to identify all subjects diagnosed with late-onset CAH or NC-CAH at a single institution during the last decade. Eighteen subjects were identified. Fourteen were diagnosed as NC-CAH 21-hydroxylase deficiency and four with NC-CAH 3-beta hydroxysteroid dehydrogenase (3βHSD) deficiency. The approach to evaluation was different according to the provider. Re-evaluation of steroid hormone concentrations using updated diagnostic criteria revealed one patient had ACTH-stimulated hormone concentrations consistent with classic CAH (non-salting wasting variant) and four patients initially thought to have NC-CAH 3βHSD had steroid hormone concentrations consistent with premature adrenarche. Age and clinical presentation did not differentiate subjects with NC-CAH from those with premature adrenarche. Skeletal age was ≥ to 2 standard deviations advanced only in those patients with NC-CAH. Variations in the diagnostic approach to evaluate children for NC-CAH exist. We provide a practical algorithmic recommendation, incorporating the most recent diagnostic guidelines, to aid the clinician in the evaluation of this disorder.

Congenital Adrenal Hyperplasia: 20-Year Experience in Southern Thailand

Background: Congenital adrenal hyperplasia (CAH) is a group of inherited disorders resulting deficiency of enzymes in the synthesis of cortisol. The clinical symptoms vary depending upon the specific enzymatic deficiency. Aim: To depict the clinical features, and laboratory and hormonal studies of CAH patients. Subjects and method: The medical records of pediatric patients diagnosed with CAH at Songklanagarind Hospital during 1991-2010 were reviewed. Results: There were 61 CAH patients. The most common type was 21-hydroxylase deficiency, salt-wasting type (21-OH, SW) (57.4%), followed by 21-hydroxylase deficiency, simple virilizing type (21-OH, SV) (31.1%). All patients with 20, 22-desmolase deficiency (n=4), 21-OH, SW (n=35) and 3β-hydroxysteroid dehydrogenase deficiency (n=3) presented with dehydration at the median age of 1.8 months. Genital ambiguity was found in 53% of girls with 21-OH, SW. Nineteen patients with 21-OH, SV presented with enlarged clitoris/penis at the median age of 5 years. The median cortisol level after ACTH stimulation was < 18 ug/dL in all types, except 19 patients with 21-OH, SV, in which the median cortisol was 19.49µg/dL. The basal 17-OHP level of these 19 patients was markedly elevated (5,985 ng/dL). All patients, except one, were assigned correctly as a boy or girl at the initial presentation. Conclusions: The most common type of CAH in our institute was 21-hydroxylase deficiency. The most common clinical manifestation in the newborn period is dehydration, and in the childhood period is the enlarged clitoris/penis. The most useful investigation for definite diagnosis of 21-hydroxylase deficiency is basal 17-OHP level.

Congenital adrenal hyperplasia: hospital based study

Background: Congenital adrenal hyperplasia is a family of autosomal recessive disorders of cortisol biosynthesis. Depending on the enzymatic step that is deficient, there may be signs, symptoms, and laboratory findings of mineralocorticoid deficiency or excess; incomplete virilization or premature puberty in affected males; and virilization or sexual infantilism in affected females. The most frequent is 21-hydroxylase enzyme deficiency, accounting for more than 90% of cases.Objectives: to review cases of congenital adrenal hyperplasia registered in children welfare teaching hospital- medical city- Baghdad.Patients and method: This study included all patients who were presented and registered in the endocrine clinic of the children welfare teaching hospital- medical city complex as a case of congenital adrenal hyperplasia from the 1st of January 1990 till the 1st of Jun 2009. Demographic informations together with epidemiological, clinical, diagnostic and therapeutic data of the patients were collected.Results: The total number of patients was 60 patients with mean age (6.321) +/- (3.996) SD and male to female ratio of 2:3. Seventy percent of patients presented within the 1st 6 months of life, 61.9% of them were females. Thirty-one (51.7%) patients were delivered in the hospital including 72% of those who were presented within the 1st month. Forty six (76.7%) patients were presented with ambiguous genitalia with or without other presentations, 8 (13.3%) patients presented with salt losing only and 6(10%) patients presented with pseudo precocious puberty with or without other presentations. Consanguinity between the parents was present in 86.7% of patients, 33.3% of patients had positive family history of similar condition, 36.7% of patients had positive family history of neonatal death due to dehydration or abortion and only 3.3% of patients had history of hormonal therapy during pregnancy. Twenty two (36.7%) patients were reared with false sex, 95.5% of them were females reared as males, 33.3% of them accept to change their names &amp; sex of rearing to definitive sex asfemales and one male (4.5%) patient reared as female had change his name and sex to male. Seventy percent of patients were diagnosed as 21 hydroxylase deficiency, both salt loser (71.4%) and non salt loser (28.6%), (10%) as 11 hydroxylase deficiency, (18.3%) as 3β hydroxysteroid dehydrogenase deficiency both salt loser (54.5%) and non salt loser (45.5%) and (1.7%) as17 hydroxylase deficiency.Conclusions: The commonest form of congenital adrenal hyperplasia in Iraq is 21 hydroxylase deficiencies. There was delay in the diagnosis in spite of hospital delivery, and this may lead to psycho-social problems for the patients and their families regarding changing the sex of rearing. Many patients having genital anomalies did not operate upon yet.

Clinical, hormonal, and molecular-genetic characteristics of two cases of abnormal sex formation (ASF) in 46XY subjects caused by type 3 17-beta hydroxysteroid dehydrogenase deficiency

Type 3 17-beta hydroxysteroid dehydrogenase (17HSD3) deficiency is a rare form of abnormal sex formation (ASF) in 46XY subjects in which the conversion of androstendione to testosterone is blocked; this defect results in compromised masculinization of the external genitalia during the intrauterine development. A distinctive feature of this form of sex development is masculinization at puberty due to the extragonadal conversion of androstendione to testosterone. Two clinical cases are reported: both girls were born with the female-type of external genitalia and 46XY karyotype, but progressive virilization in the pubertal period gave reason to suspect diagnosis of 17HSD3 deficiency. In both cases, this diagnosis was confirmed in molecular genetic studies (the following mutations were identified in the HSD17B3 gene: c.728-734delGATAACCp.1244fsX254/c.277+4A&gt;T and c.277+4A&gt;T). These two cases are the first reports of 17HSD3 deficiency in the Russian literature.

Isolated mild clitoral hypertrophy may reveal 46,XY disorders of sex development in infancy due to 17βHSD-3 defect confirmed by molecular analysis

Aims. 17-β-Hydroxysteroid dehydrogenase type 3 (17βHSD-3) is expressed exclusively in the testes where it converts Δ4 androstenedione (Δ4) to testosterone (T). Here, we report a patient with a rare mutation at a critical site in HSD17B3 gene leading to deficiency of 17β HSD-3 enzyme.Methods. We describe a 3-year old healthy female of consanguineous Lebanese descent, who presented to the endocrine service with isolated mild clitoromegaly. Adrenocorticotropic hormone (ACTH) and human chorionic gonadotrophin (hCG) stimulation tests were performed. Genes for sex-determining region Y (SRY), steroidogenic factor-1 (SF-1) and 17βHSD-3 (HSD17B3) were sequenced.Results. The post-hCG stimulation T levels and T/Δ4 ratio was low. Patient had a 46,XY karyotype. Sequence analysis of the HSD17B3 gene revealed a homozygous R80W missense mutation on exon 3. No mutation was found in SRY and SF1 genes. Mullerian structures were not detected on pelvic imaging.Conclusions. A low T/Δ4 ratio is indicative of 17βHSD-3 deficiency and associated with isolated clitoromegaly. The R80 site is critical for NADPH binding, thus the mutation at this site leads to 17βHSD-3 deficiency presenting as 46,XY disorder of sex development.

Characterization of Disease-related 5β-Reductase (AKR1D1) Mutations Reveals Their Potential to Cause Bile Acid Deficiency

Bile acid deficiency is a serious syndrome in newborns that can result in death if untreated. 5beta-Reductase deficiency is one form of bile acid deficiency and is characterized by dramatically decreased levels of physiologically active 5beta-reduced bile acids. AKR1D1 (aldo-keto reductase 1D1) is the only known human enzyme that stereo-specifically reduces the Delta(4) double bond in 3-keto steroids and sterols to yield the 5beta-hydrogenated product. Analysis of the AKR1D1 gene in five patients with 5beta-reductase deficiency revealed five different mutations resulting in an amino acid substitution in the protein. To investigate a causal role for these observed point mutations in AKR1D1 in 5beta-reductase deficiency, we characterized their effect on enzymatic properties. Attempts to purify mutant enzymes by overexpression in Escherichia coli only yielded sufficient amounts of the P133R mutant for further characterization. This enzyme displayed a highly reduced K(m) and V(max) reminiscent of uncompetitive kinetics with 4-cholesten-7alpha-ol-3-one as substrate. In addition, this mutant displayed no change in cofactor affinity but was more thermolabile in the absence of NADPH as judged by CD spectroscopy. All mutants were compared following expression in HEK 293 cells. Although these enzymes were equally expressed based on mRNA levels, protein expression and functional activity were dramatically reduced. Cycloheximide treatment also revealed that several of the expressed mutants were less stable. Our findings show that the reported mutations in AKR1D1 in patients with 5beta-reductase lead to significantly decreased levels of active enzyme and could be causal in the development of bile acid deficiency syndrome.

A Study of Gender Outcome of Egyptian Patients with 46,XY Disorder of Sex Development

Children with disorder of sex development (DSD) may be born with ambiguous genitalia. Decision-making in relation to sex assignment has been perceived as extremely disturbing and difficult to families and health care professionals. This is mainly due to a general paucity of information about the condition and an exaggerated feeling of stigma and shame associated with genital abnormalities. This is the first study in Egypt aimed at studying the psychosexual development and gender outcome of 40 Egyptian patients with 46,XY DSD focusing on the impact of social and religious factors. The patients were subjected to history-taking, pedigree analysis, full clinical examination, and cytogenetic studies. Hormonal, radiological investigations and molecular studies were performed when possible. Accordingly, they were classified into 4 groups: (1) sex chromosome aneuploid DSD (mixed gonadal dysgenesis) and (2) disorders of gonadal development (gonadal dysgenesis); (3) androgen biosynthesis defect (5α-reductase deficiency, 17β-hydroxysteroid dehydrogenase deficiency), and (4) defect in androgen action (androgen insensitivity syndrome). The psychosexual development was assessed using adapted structured questionnaire and the Bem sex role inventory for patients below and above 12 years of age, respectively. Thirty-two patients (80%) were initially assigned as females; 3 patients with gonadal dysgenesis, 1 patient with 5α-reductase deficiency, and 1 patient with androgen insensitivity were reassigned as male. Male reassignment also was recorded in 5 patients with 17β-hydroxysteroid dehydrogenase deficiency and one of them showed sex reversal twice. Gender outcome of our patients is elusive; the social component has a significant impact on the gender outcome in our society, even more than religion. We recommend that in the future more and more patients should be analyzed as well. These studies should be designed to emphasize the quality of life of DSD patients.

Reloading Against Rare Liver Diseases

Reloading Against Rare Liver Diseases

Infant with 3 beta hydroxysteroid dehydrogenase deficiency

The Journal is the primary organ of Continuing Paediatric Medical Education in Sri Lanka. The journal also has a website. Free full text access is available for all readers.The Sri Lanka Journal of Child Health is now indexed in SciVerse Scopus (Source Record ID 19900193609), Index Medicus for South-East Asia Region (IMSEAR), CABI (Centre for Agriculture and Bioscience International Global Health Database), DOAJ and is available in Google, as well as Google Scholar.The policies of the journal are modelled on the Committee on Publication Ethics (COPE) Guidelines on Principles of Transparency and Best Practice in Scholarly Publishing. Sri Lanka Journal of Child Health is recognised by the International Committee of Medical Journal Editors (ICMJE) as a publication following the ICMJE Recommendations.

17β-Hydroxysteroid dehydrogenase-3 deficiency: From pregnancy to adolescence

Aim of this study is to report on basal clinical phenotype and follow up after diagnosis, of patients with 17beta-hydroxysteroid-dehydrogenase type 3 (17beta-HSD3) deficiency in Italy. Pediatric Endocrine Departments, University Hospitals. The cases of 5 Italian subjects affected by 17beta-HSD3 deficiency are presented in this study. Laboratory and genetic assessment. Gonadectomy and female sex assignment (4 patients) or GnRH analog therapy to regress puberty and gender identity disorder (1 patient). Presentation lasted from pregnancy (pre-natal diagnosis of a 46,XY fetus with female external genitalia) to infancy (inguinal hernia containing testes/clitoromegaly) and adolescence (virilisation). All subjects but one (subject 1, Central-Northern Italy) were from small areas of Southern Italy. Endocrine data (baseline and/or stimulated testosterone/ Delta4-androstenedione ratio) were informative. Two girls were homozygous for 17beta-HSD3 gene mutations (G289S/G289S; R80W/R80W), while the others were compound heterozygous (IVS325+4 A>T/A203V; L212Q/M235V; R80W/A235E). Four patients were confirmed as females and were well-adjusted with assigned sex; gender identity disorder improved during treatment with GnRH analog in the last subject. 17betaHSD3 deficiency may present from pregnancy to puberty for different clinical issues. Albeit testosterone/Delta4-androstenedione ratio represents the most accurate endocrine marker to diagnose the disorder, hCGstimulation is mandatory in pre-puberty. Molecular analysis of 17beta-HSD3 gene should be performed to confirm the diagnosis. Temporary GnRH analog treatment may regress gender identity disorder and provide time to confirm or change the birth sex assignment. Female individuals seems to be compliant with their sex, providing that virilisation does not occur. In Italy, the disorder seems to be more prevalent in the Southern regions and shows genetic heterogeneity.

SRD5B1 gene analysis needed for the accurate diagnosis of primary 3‐oxo‐Δ4‐steroid 5β‐reductase deficiency

We encounter hyper-3-oxo-Delta(4) bile aciduria in patients with severe cholestatic liver disease or fulminant liver failure during the neonatal period. However, simply by bile acid analysis, it is difficult to distinguish hyper-3-oxo-Delta(4) bile aciduria from primary 3-oxo-Delta(4)-steroid 5beta-reductase deficiency. To determine whether 3-oxo-Delta(4)-steroid 5beta-reductase (SRD5B1) gene analysis is required for the accurate diagnosis of 3-oxo-Delta(4)-steroid 5beta-reductase deficiency, we evaluated the laboratory data, bile acid analysis and SRD5B1 gene analysis from six patients with hyper-3-oxo-Delta(4) bile aciduria. Based upon the results, four patients who had developed neonatal liver failure were diagnosed as having neonatal hemochromatosis. Two patients with chronic cholestasis were diagnosed as having primary 3-oxo-Delta(4)-steroid 5beta-reductase deficiency by SRD5B1 gene analysis. The SRD5B1 gene in these two patients had a heterozygous mutation, G737A (Gly 223 Glu) in one patient and C217T (Arg 50 stop) in the other. Based upon our limited data, we conclude that SDR5B1 gene analysis is required for the accurate diagnosis of 3-oxo-Delta(4)-steroid 5beta-reductase deficiency. Moreover, we think that it is important to elucidate whether there is a heterozygous or a compound heterozygous mutation of the SRD5B1 gene in our two patients.

Diagnosis of 17β-hydroxysteroid dehydrogenase deficiency

17β-hydroxysteroid dehydrogenase deficiency is a rare autosomal recessive inherited disorder of sex development, affecting only 46,XY individuals. It is due to mutations in the HSD17B3 gene, encoding the 17β-hydroxysteroid-dehydrogenase type 3 enzyme. Mutated enzymes lead to absent or reduced ability to convert Δ4-androstenedione to testosterone in the testis. Affected 46,XY individuals present with testes located in the inguinal canal and underdeveloped or hypoplastic Wolffian structures, but female or ambiguous external genitalia. Such individuals are usually raised as females, but show spontaneous virilization at puberty. Correct diagnosis is mandatory to optimize treatment and follow-up. The clinical and laboratory approach, as well as the follow-up of subjects with 17β-hydroxysteroid-dehydrogenase deficiency, are detailed in this review, and the genetic mutations characterized to date are summarized.

46,XY DSD with Female or Ambiguous External Genitalia at Birth due to Androgen Insensitivity Syndrome, 5α-Reductase-2 Deficiency, or 17β-Hydroxysteroid Dehydrogenase Deficiency: A Review of Quality of Life Outcomes

Disorders of sex development refer to a collection of congenital conditions in which atypical development of chromosomal, gonadal, or anatomic sex occurs. Studies of 46,XY DSD have focused largely on gender identity, gender role, and sexual orientation. Few studies have focused on other domains, such as physical and mental health, that may contribute to a person's quality of life. The current review focuses on information published since 1955 pertaining to psychological well-being, cognition, general health, fertility, and sexual function in people affected by androgen insensitivity syndromes, 5-α reductase-2 deficiency, or 17β-hydroxysteroid dehydrogenase-3 deficiency—reared male or female. The complete form of androgen insensitivity syndrome has been the focus of the largest number of investigations in domains other than gender. Despite this, all of the conditions included in the current review are under-studied. Realms identified for further study include psychological well-being, cognitive abilities, general health, fertility, and sexual function. Such investigations would not only improve the quality of life for those affected by DSD but may also provide information for improving physical and mental health in the general population.

Comparison of sex steroid synthesis between neonatal and adult rat hippocampus

Management of impalpable gonads in intersex patients remains a challenging problem. Since laparoscopic gonadectomy or gonadal preservation has been used in the management of impalpable gonads in the normal male population, laparoscopy can be an alternative method in the treatment of intersex patients.Laparoscopic operations were performed on 6 patients with intersex conditions, including the testicular feminization syndrome in 2, 17 beta-hydroxysteroid dehydrogenase deficiency in 1, 5 alpha-reductase deficiency in 1 and mixed gonadal dysgenesis in 2.Laparoscopic gonadal biopsy, gonadectomy and hysterosalpingectomy were done in select patients.Although the initial diagnoses were made by phenotypic presentation, and biochemical and cytogenetic studies, laparoscopy had an important role in defining the internal ductal and gonadal structures to confirm the diagnosis, and served as an efficient method for gonadectomy and removing structures contrary to the assigned gender.