Aetiological bases of 46,XY disorders of sex development in the Hong Kong Chinese population.
OBJECTIVE
Disorders of sex development are due to congenital defects in chromosomal, gonadal, or anatomical sex development. The objective of this study was to determine the aetiology of this group of disorders in the Hong Kong Chinese population.


METHODS
Five public hospitals in Hong Kong.


METHODS
Patients with 46,XY disorders of sex development under the care of paediatric endocrinologists between July 2009 and June 2011.


METHODS
Measurement of serum gonadotropins, adrenal and testicular hormones, and urinary steroid profiling. Mutational analysis of genes involved in sexual differentiation by direct DNA sequencing and multiplex ligation-dependent probe amplification.


RESULTS
Overall, 64 patients were recruited for the study. Their age at presentation ranged from birth to 17 years. The majority presented with ambiguous external genitalia including micropenis and severe hypospadias. A few presented with delayed puberty and primary amenorrhea. Baseline and post-human chorionic gonadotropin-stimulated testosterone and dihydrotestosterone levels were not discriminatory in patients with or without AR gene mutations. Of the patients, 22 had a confirmed genetic disease, with 11 having 5α-reductase 2 deficiency, seven with androgen insensitivity syndrome, one each with cholesterol side-chain cleavage enzyme deficiency, Frasier syndrome, NR5A1-related sex reversal, and persistent Müllerian duct syndrome.


CONCLUSIONS
Our findings suggest that 5α-reductase 2 deficiency and androgen insensitivity syndrome are possibly the two most common causes of 46,XY disorders of sex development in the Hong Kong Chinese population. Since hormonal findings can be unreliable, mutational analysis of the SRD5A2 and AR genes should be considered the first-line tests for these patients.
Department of Pathology, Queen Elizabeth Hospital, Jordan, Hong Kong.
Angel O K
AO
Chan
Department of Paediatrics, Queen Elizabeth Hospital, Jordan, Hong Kong.
W M
WM
But
Department of Paediatrics and Adolescent Medicine, Caritas Medical Centre, Shamshuipo, Hong Kong.
C Y
CY
Lee
Department of Paediatrics and Adolescent Medicine, Kwong Wah Hospital, Yaumatei, Hong Kong.
Y Y
YY
Lam
Department of Paediatrics and Adolescent Medicine, United Christian Hospital, Kwun Tong, Hong Kong.
K L
KL
Ng
Department of Paediatrics and Adolescent Medicine, Princess Margaret Hospital, Laichikok, Hong Kong.
P Y
PY
Loung
Department of Paediatrics and Adolescent Medicine, United Christian Hospital, Kwun Tong, Hong Kong.
Aimen
A
Lam
Department of Pathology, Queen Elizabeth Hospital, Jordan, Hong Kong.
C W
CW
Cheng
Department of Pathology, Queen Elizabeth Hospital, Jordan, Hong Kong.
C C
CC
Shek
Department of Pathology, Queen Elizabeth Hospital, Jordan, Hong Kong.
W S
WS
Wong
Department of Pathology, Queen Elizabeth Hospital, Jordan, Hong Kong.
K F
KF
Wong
Department of Paediatrics, Queen Elizabeth Hospital, Jordan, Hong Kong.
M Y
MY
Wong
Department of Paediatrics, Queen Elizabeth Hospital, Jordan, Hong Kong.
W Y
WY
Tse
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000172:deficiency; D058489:46, XX Disorders of Sex Development / Q000209:etiology; D000293:Adolescent; D000568:Amenorrhea / Q000209:etiology; D013734:Androgen-Insensitivity Syndrome / Q000209:etiology; D044466:Asian People; D002648:Child; D002675:Child, Preschool; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000172:deficiency; D000013:Congenital Abnormalities / Q000209:etiology; D004252:DNA Mutational Analysis; D013196:Dihydrotestosterone / Q000097:blood; D058490:Disorder of Sex Development, 46,XY / Q000097:blood / Q000209:etiology* / Q000652:urine; D005260:Female; D052159:Frasier Syndrome / Q000209:etiology; D005832:Genital Diseases, Male / Q000209:etiology; D006062:Gonadotropins / Q000097:blood; D006723:Hong Kong; D006801:Humans; D007021:Hypospadias / Q000209:etiology; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009095:Mullerian Ducts / Q000002:abnormalities; D009154:Mutation; D010413:Penis / Q000002:abnormalities; D011628:Puberty, Delayed / Q000209:etiology; D054339:Steroidogenic Factor 1 / Q000235:genetics; D013739:Testosterone / Q000097:blood
D006062:Gonadotropins; C515057:NR5A1 protein, human; D054339:Steroidogenic Factor 1; D013196:Dihydrotestosterone; D013739:Testosterone; D002786:Cholesterol Side-Chain Cleavage Enzyme; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C476567:steroid-5alpha-reductase type 2
Disorders of sex development; Female; Male; Mutation/genetics