CASE REPORT
Indonesia Journal of Biomedical Science (IJBS) 2026.
Volume 20.
Number 1: 23-28 P-ISSN.
E-ISSN.
Published by Indonesia Journal of Biomedical Science Diagnostic challenges in 46.
XY disorder of sex development due to 5-alpha-reductase type 2 deficiency: a case report Ni Kadek Risa Astria1*.
I Made Arimbawa2.
I Made Darma Yuda2
ABSTRACT
Backgrounds: Disorders of sex development (DSD) represent congenital conditions characterized by atypical chromosomal, gonadal, or anatomical sex differentiation.
Among 46,XY DSD, 5-alpha-reductase type 2 deficiency .
-ARD) is a rare autosomal recessive disorder caused by impaired conversion of testosterone to dihydrotestosterone (DHT), resulting in undervirilization at birth.
Early recognition is often challenging, particularly in resource-limited settings, leading to delayed diagnosis until virilization becomes apparent during childhood or puberty.
Case Presentation: We report the case of an 8-year-old child raised as male who presented with ambiguous genitalia and absent testes.
The parents noted genital atypia since birth, but financial barriers delayed medical evaluation until age two.
The patient demonstrated normal growth and developmental milestones.
Physical examination revealed male-type external genitalia with a glans penis, perineal urethral opening, non-palpable testes, and Prader stage 4Ae5 virilization.
Abdominal ultrasonography showed no scrotal or inguinal testes and the absence of a uterus.
Diagnostic laparoscopy revealed a fibrotic right testis, while the left testis could not be Cytogenetic analysis demonstrated a 46.
XY karyotype.
Hormonal evaluation showed markedly low baseline DHT .
4 nmol/L) with a disproportionately low increase after -hCG stimulation despite a significant rise in testosterone .
to 488 ng/dL), confirming impaired conversion to DHT consistent with 5-ARD.
A multidisciplinary team concluded that further management would include DHT therapy, staged genitourinary reconstruction, psychological support, and legal proceedings for sex assignment correction, as the patient was registered female at birth.
Conclusion: This case underscores the importance of early clinical recognition and timely, coordinated diagnostic evaluation in suspected 5-ARD, particularly in resource-limited settings.
Prompt identification facilitates appropriate multidisciplinary management and may improve both clinical and psychosocial outcomes.
Pediatric Residency Program.
Department of Child Health.
Faculty of Medicine.
Universitas Udayana / Prof.
Dr.
Ngoerah General Hospital Department of Child Health.
Medical Faculty.
Universitas Udayana/Prof.
Ngoerah General Hospital *Correspponding to:
Ni Kadek Risa Astria.
Pediatric Residency Program.
Department of Child Health.
Faculty of Medicine.
Universitas Udayana / Prof.
Dr.
Ngoerah General Hospital.
risaastria95@gmail.
Received: 2026-02-08 Accepted: 2026-03-29 Published: 2026-04-17 Keywords: ambiguous genitalia.
case report.
5-alpha-reductase deficiency.
disorder of sex development.
46,XY DSD.
Cite this Article: Astria.
Arimbawa.
Yuda.
Diagnostic challenges in 46.
XY disorder of sex development due to 5-alpha-reductase type 2 deficiency: a case reportt.
IJBS 20.
: 23-28.
DOI: 10.
15562/ijbs.
INTRODUCTION
Disorders of sex development (DSD) comprise a heterogeneous group of congenital conditions characterized by atypical development of chromosomal, gonadal, or anatomical sex.
Classified by the Lawson Wilkins Pediatric Endocrine Society and the European Society for Paediatric Endocrinology into sex chromosomal DSD, 46.
XX DSD, and 46.
XY DSD, these conditions collectively occur in approximately 1 in 4,500Ae5,500 live births.
Among them, 46.
XY DSD arises from impaired androgen production or action, frequently resulting in undervirilization of individuals with a male karyotype.
One important but rare cause of 46.
XY DSD is 5-alpha reductase type 2 deficiency .
-ARD), an autosomal recessive disorder caused by mutations in the SRD5A2 gene, which encodes the enzyme responsible for converting testosterone (T) into the more potent androgen dihydrotestosterone (DHT).
DHT plays a crucial role in the differentiation of external male genitalia and prostate development in utero.
thus, deficiency leads to a spectrum of phenotypes ranging from Published by Indonesia Journal of Biomedical Science | IJBS 2026.
: 23-28 | doi: 10.
15562/ijbs.
Open access:
http://ijbs-udayana.
female-appearing external genitalia to varying degrees of undervirilization at Despite this.
Wolffian structures typically differentiate normally because their development depends primarily on testosterone rather than DHT.
A detailed history is essential to uncover any relevant familial patterns, including genital or urologic occurrences of ambiguous genitalia.
It is important to determine whether consanguinity is present, as this increases the probability of autosomal recessive Additional key points include CASE REPORT histories of amenorrhea, infertility, or premature menopause.
Maternal factors should also be explored, such as previous spontaneous miscarriages, stillbirths, or unexplained neonatal deaths that may reflect an unrecognized adrenal crisis, as well as exposure to medications during pregnancy that could cause fetal Furthermore, clinical signs, especially manifestations of androgen excess such as hirsutism or virilization, may indicate an underlying endocrine disorder contributing to the Clinically, affected individuals often present in infancy with ambiguous genitalia, micropenis, hypospadias, inguinal masses, or labioscrotal fusion.
However, in cases where genitalia appear typically female at birth, diagnosis may be delayed until puberty, when rising testosterone levels lead to spontaneous virilization, including voice deepening, phallic enlargement, and increased muscle mass.
4 This unexpected pubertal transition can trigger significant psychosocial distress, prompting reevaluation of sex assignment and gender Biochemical evaluation typically reveals normal or elevated testosterone levels, reduced DHT, and an increased T/DHT ratio, while definitive diagnosis relies on genetic confirmation of SRD5A2 Management of 5-ARD is complex and requires a multidisciplinary approach, integrating pediatric endocrinology, urology, psychology, genetics, psychiatry.
Decisions sex assignment, timing of surgical intervention, and long-term follow-up must consider phenotypic presentation, anticipated pubertal changes, fertility potential, and the evolving gender identity of the patient.
As evidenced in several studies, early diagnosis and coordinated care are essential for optimizing psychosocial and functional outcomes.
However, despite existing knowledge, there remains a significant gap in the literature regarding the real-world diagnostic challenges and delays in low-resource settings, particularly in developing countries such as Indonesia, where socioeconomic barriers, limited access to specialized care, and cultural considerations may complicate early identification and management of DSD.
Delayed diagnosis may lead to prolonged uncertainty in sex assignment, suboptimal psychosocial burden for both patients and Therefore, this case report aims to highlight the diagnostic challenges, the impact of socioeconomic constraints on delayed presentation, and the complexity of multidisciplinary management of 5-ARD within the Indonesian healthcare context, emphasizing the importance of early recognition and coordinated evaluation to improve patient outcomes.
CASE DESCRIPTION
An 8-year-old child raised as male was referred for evaluation of ambiguous genitalia and non-palpable testes.
At birth, the patient was assigned female based on external genital appearance.
Progressive clitoral enlargement during early childhood resulted in a phallic structure, while urination remained through a perineal urethral opening.
Financial constraints delayed medical evaluation until the age of two years.
The patient had no significant past medical history and demonstrated Figure 1.
Physical characteristics of the patient illustrate the male type of body contour.
Figure 2.
Clinical photograph showing external genitalia Published by Indonesia Journal of Biomedical Science | IJBS 2026.
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15562/ijbs.
CASE REPORT
normal growth and developmental On examination, the patient was in stable condition with normal vital signs and appropriate anthropometric nutritional status.
Systemic examination was unremarkable.
Genital examination revealed male-type external genitalia with a phallic structure and visible glans penis, perineal urethral opening .
, and bilaterally non-palpable testes.
These findings were consistent with Prader stage 4Ae5 virilization (Figures 1 and .
Abdominal ultrasonography performed in July 2023 revealed the absence of testicular structures in the scrotal and inguinal regions, with no visualization of a uterus.
The presence of intra-abdominal testes could not be confirmed.
Diagnostic laparoscopy in December 2023 identified a fibrotic right testis, while the left testis was not visualized.
A cervix-like structure with a patent lumen was also observed.
Subsequently, -hCG stimulation testing with serial hormonal assessment was performed in 2024.
Cytogenetic analysis demonstrated a normal male karyotype .
,XY), with no structural or numerical chromosomal abnormalities, confirming the diagnosis of 46,XY DSD (Figure .
Hormonal evaluation showed normal 17-hydroxyprogesterone .
markedly low dihydrotestosterone (DHT) .
4 nmol/L).
Baseline testosterone prior to -hCG stimulation was 44 ng/dL, which increased to 488 ng/dL post-stimulation, while DHT rose only minimally .
to 14 ng/dL).
This discordant response, reflected by an elevated testosterone-to-DHT ratio, is consistent with impaired conversion of testosterone to DHT, confirming 5-alphareductase deficiency.
A multidisciplinary team meeting was conducted in May 2025 to determine further management.
The patient was approaching puberty and had developed a male gender identity.
However, the prognosis for fertility was considered poor, and postoperative penile function was expected to be limited.
The agreed management plan included topical DHT (Andracti.
therapy for 4Ae5 months, followed by staged genitourinary .
rethroplasty orthoplast.
, along with psychological Figure 3.
Cytogenetic report The urology team noted that the right testis was fibrotic and the left testis was not identifiable, further reducing fertility potential.
Access to DHT therapy remains a challenge, as the medication is not available domestically and requires special authorization for importation.
Psychiatric mild social difficulties, and ongoing counselling for the patient and family was Growth and development assessments were within normal limits.
From a legal perspective, correction of sex assignment requires a formal court decision, as the patient was registered female at birth.
The process is currently ongoing, supported by a multidisciplinary medical report.
DISCUSSION
Individuals who exhibit congenital variations in the development of chromosomal, gonadal, or anatomical sex are categorized as having a Disorder of Sex Development (DSD).
These conditions frequently manifest with atypical or ambiguous genitalia.
Historically, the term intersex was applied, with cases further classified female pseudohermaphroditism, or true However, following the 2006 consensus statement, a revised terminology was adopted, replacing intersex with Disorder of Sex Development and reorganizing the classification into three major groups: 46.
XX DSD, 46.
XY DSD, and sex chromosome DSD.
7,8 Sexual Published by Indonesia Journal of Biomedical Science | IJBS 2026.
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differentiation is regulated by a complex interaction of genetic and hormonal however, detailed embryological mechanisms are beyond the scope of this In the context of this case, impaired reduced conversion of testosterone to dihydrotestosterone (DHT), plays a central role in the development of undervirilized external genitalia in individuals with a 46,XY karyotype.
9,10
A comprehensive diagnostic workup, including clinical assessment, hormonal evaluation, radiologic imaging, and chromosomal analysis, is essential for identifying cases of DSD.
Among the genitalia represent the most frequent clinical presentation.
The incidence of genital ambiguity differs between regions and is notably influenced by the prevalence of consanguineous marriages within a Research from countries with high rates of consanguinity demonstrates a greater occurrence of ambiguous genitalia, with reported incidences of approximately 1 in 2,500 live births in Saudi Arabia and 1 in 3,000 in Egypt.
11 External genital ambiguity may be identified at birth or present later, particularly in cases where genitalia appear typically female initially but virilization occurs at puberty.
In high-resource settings, early evaluation is typically performed shortly after birth.
However, in resourcelimited settings, delayed diagnosis remains a significant challenge due to socioeconomic barriers, limited access to specialized care, and sociocultural CASE REPORT Figure 4.
The process of sexual differentiation.
13 This was evident in the present case, where early signs of genital atypia were recognized but formal evaluation was delayed, contributing to late diagnosis and its associated clinical and psychosocial Clinically, this patient presented with Prader stage 4Ae5 virilization, characterized by a phallic structure, perineal urethral opening, and non-palpable testes, consistent with severe undervirilization in 46,XY DSD.
The patientAos male gender identity and progression toward puberty further supported the need for timely diagnostic clarification and management.
Traditionally, the diagnosis of 5-reductase type 2 deficiency relies on biochemical evaluation, particularly the testosterone-to-dihydrotestosterone (T/ DHT) ratio following -hCG stimulation.
In normal individuals, both testosterone and DHT increase proportionally after In contrast, patients with 5-ARD exhibit a marked increase in testosterone with a disproportionately low rise in DHT, resulting in an elevated T/ DHT ratio.
This biochemical pattern helps differentiate 5-ARD from other causes of 46,XY DSD, such as androgen insensitivity syndrome, where DHT levels are typically 15 In this case, testosterone increased substantially following -hCG stimulation .
to 488 ng/dL), while DHT showed only a minimal rise .
to 14 ng/ Figure 5.
Prader Staging and virilization of the external genitalia.
dL), demonstrating a clear discordance consistent with impaired enzymatic These findings strongly support the diagnosis of 5-ARD.
However, it is important to note that the T/DHT ratio has variable sensitivity and specificity and may be inconclusive in partial enzyme deficiency, limiting its role as a standalone diagnostic tool.
15 A key limitation of this case is the absence of molecular genetic testing to confirm mutations in the SRD5A2 gene.
This reflects a common challenge in resource-limited settings, where access to advanced diagnostic modalities remains restricted.
The lack of genetic confirmation may affect diagnostic certainty and limit genotype-phenotype correlation, which can be important for prognostication and family counselling.
The SRD5A2 gene encodes the 5-reductase type 2 enzyme responsible for converting testosterone to DHT.
Mutations in this gene result in varying degrees of enzymatic dysfunction, leading to a spectrum of phenotypic presentations depending on residual enzyme activity.
Management of 5-ARD is complex and requires a multidisciplinary approach.
Historically, many patients were assigned female at birth.
however, studies indicate that a significant proportion transition to male gender identity during puberty.
In this case, the patient was raised as male and demonstrated male gender identification, which guided clinical decision-making.
16 Delayed presentation in this patient significantly affected management options, particularly fertility Published by Indonesia Journal of Biomedical Science | IJBS 2026.
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CASE REPORT
preservation, as early orchidopexy was not The presence of a fibrotic testis and non-identifiable contralateral gonad further suggests a poor fertility prognosis.
At present, no standardized guidelines exist for the management of children with 5-reductase deficiency.
Because these patients often present with ambiguous genitalia, many were traditionally assigned a female gender at birth.
however, evidence now indicates that more than 60% of those raised as female later transition to a male gender identity during puberty.
In early infancy, the condition can be clinically challenging to differentiate from androgen insensitivity syndrome, and the testosterone-to-DHT ratio may be inconclusive, particularly in individuals with partial enzyme activity, highlighting the importance of definitive molecular testing to support timely clinical decisions.
Although external genital virilization is impaired, fetal androgen exposure to the brain remains intact, which is believed to contribute to the higher prevalence of gender dysphoria in this population.
Research suggests that increased gray matter volume in brain regions typically associated with males correlates with elevated fetal testosterone levels.
These permanent neurodevelopmental effects occur through direct testosterone action during prenatal life, separate from DHTdependent With the rise in testicular testosterone production during puberty, these prenatally established neural pathways are thought to become functionally active, potentially explaining the higher frequency of female-to-male gender transition during adolescence.
19 In this case, the patient was raised as a male, given a masculine name, and registered as male.
His peers are not aware of his condition and have been recognized as male since younger age.
Following detailed counselling and examination, a team of pediatric endocrinologists, pediatric urologists, gynecologists, psychiatrists, radiologists, and a forensic physician, the patient planned to undergo surgical cordectomy, and orthoplasty, with possible excision of any remaining vestibulum by the urogynaecology team.
Given that orchidopexy should ideally be performed before one year of age, the patient is now almost certainly infertile.
A decline in quality of life among children with DSD is largely linked to psychosocial difficulties, including gender dysphoria, parental or familial rejection, shame, and social withdrawal.
Study from Raza J et al emphasizes that caring for children with DSD presents significant mental health and psychosocial Mismatch between assigned sex and physical characteristics can hinder psychosocial adjustment and lead to considerable emotional distress, further shaped by variations in family education, socioeconomic circumstances, religious beliefs, and differences in access to specialized healthcare.
An international survey also noted that only 41% of centers have adequate expertise in DSD care, underscoring the need for routine psychosocial assessment in all pediatric DSD cases.
Management of patients with DSD encompasses not only clinical and hormonal considerations but also complex legal and ethical challenges, particularly in countries with rigid binary sex-registration systems such as Indonesia.
At birth, every individual must be registered as either male or female, leaving no legal space for variations of sex characteristics, which may result in misclassification and later difficulties when patients seek correction of their legal documents.
Many patients with DSD experience obstacles in obtaining legal gender recognition, as court approval is required to change sex markers, often demanding extensive medical testimonies and expert evidence.
This process can be emotionally taxing and financially burdensome for families.
Ethically, early surgical interventions performed without the patientAos consent, traditionally aimed at AunormalizingAy genital appearance, raise concerns regarding bodily autonomy, the risk of irreversible harm, and the longterm psychological impact.
20,21
International human rights frameworks increasingly advocate delaying non-urgent genital surgeries until the individual is mature enough to participate in decision-making.
In Indonesia, stigma and limited understanding of intersex variations further complicate these issues, exposing patients and families to Published by Indonesia Journal of Biomedical Science | IJBS 2026.
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discrimination in healthcare, education, and society.
Therefore, ethically sound management requires a multidisciplinary approach grounded in informed consent, psychosocial support, and respect for bodily integrity.
At the same time, legal reforms are needed to ensure accessible gender recognition procedures and protection from discrimination for individuals with DSD.
20,21 In this case, from a legal perspective, because the patient was registered as female at birth, a court ruling is required to authorize a change in legal sex, supported by expert documentation from the hospital.
Consequently, further medical treatment will await the legal DHT procurement is in progress, and continued psychosocial support
is crucial, with realistic expectations regarding future fertility and sexual
CONCLUSION
This case highlights a 46,XY disorder of sex development due to 5-alpha-reductase type 2 deficiency .
-ARD), characterized by ambiguous genitalia at birth, delayed diagnosis, and progressive virilization.
The diagnosis was established through clinical and a characteristic hormonal profile demonstrating impaired conversion of testosterone to dihydrotestosterone.
Delayed socioeconomic constraints contributed to late diagnosis, limiting fertility potential and complicating management.
This case underscores the importance of early recognition and timely diagnostic evaluation in suspected DSD to optimize clinical and psychosocial outcomes.
Management requires a multidisciplinary approach, including hormonal therapy, support, and legal consideration for sex reassignment.
In resource-limited settings, barriers such as restricted access to therapy and legal processes may further delay definitive management.
Overall, this report emphasizes the need for improved awareness, early referral systems, and coordinated care to enhance outcomes in patients with DSD, particularly in developing healthcare settings.
CASE REPORT
CONSENT FOR PUBLICATION
Written informed consent for publication of the clinical information and accompanying images was obtained from the patientAos parent.
All efforts were made to protect the patientAos identity, and no identifying information is included in this The authors carefully reviewed and validated all AI-assisted content and assume full responsibility for the accuracy and integrity of the manuscript.
REFERENCES