Tesis

Mutasi Gen CYP21 dan Profil Klinis Anak dengan Hiperplasia Adrenal Kongenital = CYP21 Mutation and Clinical Manifestation of Children with Congenital Adrenal Hyperplasia

Latar belakang. Hiperplasia adrenal kongenital (HAK) adalah suatu kelainan genetik yang bersifat autosomal resesif. Lebih dari 90% kasus terjadi akibat defisiensi enzim 21-hidroksilase (21-OHD) yang disebabkan oleh mutasi gen CYP21.
Tujuan. Mengetahui profil mutasi CYP21 terhadap profil klinis anak dengan HAK di Indonesia.
Metode. Studi deskriptif retrospektif dilakukan selama Oktober-Desember 2014.
Subjek adalah anak HAK yang terdaftar di Klinik Endokrinologi Anak RSCM dan pernah dilakukan pemeriksaan mutasi gen CYP21. Data diambil dari anamnesis terhadap orangtua, rekam medis dan register HAK tahun 2009-2014.
Hasil penelitian. Didapatkan total subjek sebesar 45 subjek (37 perempuan, 8 lelaki) dengan profil klinis tipe salt wasting (SW) 33 subjek, simple virilizing (SV) 10 subjek, dan non-classic (NC) 2 subjek. Median usia saat terdiagnosis pada tipe SW usia 1 bulan (0-3 bulan), tipe SV usia 3 tahun (2-6 tahun), tipe NC usia 5 tahun. Keluhan utama terbanyak adalah genitalia ambigus (60%). Subjek perempuan mengalami kesalahan penentuan jenis kelamin saat lahir (32,4%) dan memiliki perilaku maskulin (24,3%). Tiga jenis mutasi ditemukan pada dua subjek, dua jenis mutasi ditemukan pada 19 subjek, mutasi R356W saja dialami oleh 9 pasien, dan mutasi I172N saja ditemukan pada 15 pasien. Mutasi I172N ditemukan pada 80% alel, R356W pada 66,7% alel, dan delesi/LGC pada 4,4% alel. Tipe SW yang mengalami mutasi delesi/LGC dan atau R356W sebesar 63,6%.
Simpulan. Manifestasi klinis terbanyak pada penelitian ini adalah tipe SW dengan mutasi R356W dan atau delesi/LGC. Pemeriksaan mutasi gen CYP21
bermanfaat untuk konseling genetik, diagnosis prenatal dan tata laksana pada keluarga yang memiliki risiko HAK.
Kata kunci: hiperplasia adrenal kongenital, defisiensi 21-hidroksilase, mutasi CYP21.



Background. Congenital adrenal hyperplasia (CAH) is an autosomal recessive genetic disorder. More than 90% of cases are due to 21-hydroxylase deficiency which caused by CYP21 mutation.
Objective. Study the characteristic of CYP21 mutation and clinical manifestation in children with CAH in Indonesia.
Method. A descriptive retrospective study was performed during October-December 2014. Subjects were CAH children who were admitted to Pediatric
Endocrinology Cipto Mangunkusumo hospital and tested for CYP21 gene mutation. Data were taken based on parents’ interview, medical records and CAH
registry during 2009-2014.
Results. A total of 45 subjects (37 girls, 8 boys) participated, with clinical profile of salt wasting (SW) type found in 33 subjects, simple virilizing (SV) in 10 subjects, and non-classical (NC) type in two subjects. Median age of diagnosis in SW type is 1 month old (0-3 month), SV type is 3 years old (2-6 years), NC type is 5 years old. Ambigous genitalia was the major chief complaint (60%). Girls experienced gender reassessment (32,4%) and show masculine behavior (24,3%). Three types of mutations were found in two patients, two types of mutations (R356W and I172N) in 19 patients, only R356W mutation in 9 patients, and only I172N mutation in 15 patients. I172N mutation was found in 80% alleles,
followed by R356W in 66,7% alleles, and deletion/LGC in 4,4% alleles. In the SW form, 63,6% subjects had deletion and/or R356W mutation.
Conclusion. The most common clinical manifestation in this study is SW type with deletion/LGC and or R356W mutation. CYP21 mutation analysis may
provide important information for genetic counseling, prenatal diagnosis and management of families at risk for CAH.
Keywords: congenital adrenal hyperplasia, 21-hidroxylase deficiency, CYP21 mutation.