Bambang Tridjaja

Vitamin D profile in healthy children aged 7-12 years old in Indonesia

Background The recent data on the vitamin Dshowed a surprising result, which exhibited in high prevalence of vitamin D deficiency and insufficiency in children and adolescence. Thisnot only occurs in country that lies in high latitude but also in sun rich country. Many factors contributing to this condition, including changing in life style. No data available regarding vitamin D status in healthy children in Indonesiaand this will be the first study addressing this issue.

Two Novel Mutations of SRD5A2 Gene in Indonesian Siblings with Clinical 5-Alpha-Reductase Deficiency

ABSTRACT Steroid 5-alpha-reductase 2 deficiency is an autosomal recessive disorder with clinical spectrum ranges from a male phenotype with hypospadia to a female phenotype with normal wolffian structures. Over 50 different mutations of SRD5A2 gene has been described in affected patients and several mutations were detected in specific populations. DNAs of two 46,XY DSD Indonesian siblings, aged 13 and 18 years old, with clinically suspected of 5-alpha-reductase deficiency and their mother were analysed for molecular defects of SRD5A2 gene. Different from other reports, in our series three mutations were found in each patient. Two novel mutations were detected in these patients and their mother, which are p.Gly34fs and c.699-1G>T. The other mutation detected was c.680G>A or p.Arg227Gln, which commonly described in Far East Asian population. Whether the p.Arg227Gln mutation is considered a polymorphism or a mutation in Indonesian population warrants further study.

Pengobatan Testosteron pada Mikropenis

Mikropenis atau hipogenitalism adalah suatu keadaan penis dengan bentuk normal namun dengan ukuran kurang dari 2.5 SD di bawah rerata menurut umur dan status perkembangan pubertas. Pengukuran penis dilakukan secara fully stretched, menggunakan spatula kayu yang diletakkan sejajar dengan dorsum penis dan ditekan sampai simfisis pubis. Panjang penis adalah jarak dari simfisis pubis sampai ujung glans penis dan tidak dalam keadaan ereksi. Pengobatan mikropenis terhadap 23 anak dengan rerata usia 9.6 tahun dilakukan dengan pemberian testosteron ester intramuskular setiap 3 minggu sebanyak 4 kali. Pasca terapi penis bertambah panjang 85% dibandingkan sebelum terapi. Tidak terlihat adanya pertambahan usia tulang dengan protokol yang digunakan.

Krisis Adrenal pada Bayi dengan Hiperplasia Adrenal Kongenital

Krisis adrenal adalah suatu kondisi yang terjadi akibat kegagalan kelenjar adrenal memproduksi hormon glukokortikoid dan/atau mineralokortikoid secara normal. Gejala krisis adrenal pada bayi tidak spesifik, namun diagnosis dini dan tata laksana yang tepat akan menentukan prognosis pasien. Kasus adalah By &, 19 hari datang dengan keluhan tangan dan kaki dingin, keringat dingin di kepala, tidak menangis dan kelihatan lemah sejak 4 jam sebelum masuk rumah sakit. Terdapat riwayat kematian neonatal anak sebelumnya disertai ambigus genitalia. Pada pemeriksaan fisis ditemukan syok, sesak napas dan ambigus genitalia (klitoromegali, fusi labio-skrotal dan tidak ditemukan testis). Pemeriksaan darah menunjukkan asidosis metabolik berat, hiponatremia dan hiperkalemia. Hasil analisis kromosom menunjukkan 46, XX. Kadar 17-hidroksi-progesteron 84 nmol/L (N: 0,5-6,5 nmol/L).

The prevalence of insulin resistance in patients with β -thalassemia major at Cipto Mangunkusumo Hospital

Background Diabetes mellitus is a common complication in pa- tients with thalassemia major. Iron overload plays an important role by damaging the pancreatic β-cell and the liver cell, with the con- sequences of insulin deficiency and insulin resistance. Family his- tory of diabetes mellitus is one of the critical factors for the devel- opment of glucose metabolism derangement. However, the patho- genesis of glucose metabolism derangement remains unclear. Objective To evaluate the prevalence of impaired glucose toler- ance, diabetes mellitus, and insulin resistance in patients with β- thalassemia major treated in the Thalassemia Outpatient Clinic, Department of Child Health, Cipto Mangunkusumo Hospital, Jakarta. Methods This was a descriptive cross sectional study conducted in May 2002. Forty-eight subjects aged 10 to 18 years, grouped by total volume of transfusions and family history of diabetes mellitus, underwent an oral glucose tolerance test (OGTT), serum transfer- rin saturation, and insulin level examinations. Insulin resistance was calculated from fasting plasma glucose and insulin concen- trations using the homeostasis model assessment (HOMA). Results One of 48 patients (2%) had impaired glucose tolerance at the age of 17 years. Diabetes mellitus occurred in three of 48 patients (6%) at the age of 15.5 years in one patient and 18 years in two patients. Family history of diabetes mellitus was found in 2 patients with diabetes mellitus and in the only one with impaired glucose tolerance. Insulin resistance was not detected in this study. Conclusion The prevalence of glucose metabolism derangement in patients with thalassemia major was low. No insulin resistance was found in this study

Effect of bisphosphonate treatment in osteogenesis imperfecta children in Cipto Mangunkusumo Hospital Jakarta

Results Seventy-seven OI cases (39 male), which were diagnosed at the age of 1 9 years old were recorded. Five patients underwent surgery and three patients died before commencing treatment. Nine patients received intravenous pamidronate and sixteen patients received zolendronic acid therapy. Liver and renal functions, as well as serum electrolyte levels were evaluated before and after treatment. Eight patients reported hyperthermia and three others experienced fatigue, bone pain, and abdominal pain within 24 hours of therapy. Serum calcium level decreased in eight patients. No serious adverse effects were documented.

Correlation between glycemic control and quality of life of adolescents aged 13-18 years with type 1 diabetes mellitus

The efforts to achieve good glycemic control might damage the quality of life (QoL). This issue has not been elaborated in Indonesia because there was no diabetes-specific quesionnaire available in Indonesian language previously. This study would like to find out whether there is a correlation between glycemic control and QoL of adolescents aged 13-18 years with type 1 diabetes mellitus (T1DM). Cross-sectional study was held on patients who came to The Pediatric Endocrinology Clinic of Cipto Mangunkusumo Hospital or who joinned The Endocrinology Working Group Unit of Indonesian Pediatric Society programs during October to December 2010. Glycemic control was measured by hemoglobin A1c (HbA1c) levels. The audit of diabetes dependent quality of life-teen (ADDQoL-Teen) Indonesian questionnaire was used to assess the QoL. A total of 36 adolescents participated in the study. Only seven subjects had a normal HbA1c level. Median HbA1c level was 8.7 (range, 5.6 to 15.1)%. Eighteen subjects considered their QoL as good or brilliant, while 14 subjects felt that diabetes had a negative impact. The most severe negative impact was felt on the matter of dietary aspect, but could be managed better by subjects with intensive treatment. There was no correlation between HbA1c level on the last examination and average weighted impact (AWI) score (rho = -0.15; p = 0.383) or between mean HbA1c level within 6 months and AWI score (rho = -0.15; p = 0.369). This study did not show any correlation between glycemic control and QoL of adolescents with T1DM.

Profile of Congenital Hypothyroidism in DR. Cipto Mangunkusumo Hospital

Results There were 40 children with CH included in the study. Boys 12(30 %) and girls 28(70%). Age when diagnosed 0-3 months 4(10%), 3-6 months 2(5%), 6-12 months 9 (22,5%), 1-6 years 20(50%), 6-14 years 5(12,5%). Clinical manifestation: delayed development 27,5%, underweight 17,5%, acute respiratory infection 15%, constipation 12,5%, hypotonia 7,5%, speech delay 5%, short stature 5%, enlarged tongue 2,5%, vomite 2,5%, icteric 2,5%, enlarged lymph node of colli 2,5%. We found suspect down syndrome 4(10%), severe malnutrition 4(10%), short stature 3(7,5%), mental retardation 2(5%).

Relapse in pituitary adenoma after resection

Pituitary adenoma in children is rarely reported. Acromegaly is one of clinical manifestation in GH releasing-pituitary adenoma. Recurrence of clinical manifestation after resection must be evaluated for possibility of pituitary adenoma relapse. N,male,15-yo, came to pediatric endocrinology outpatient clinic with the main complain of acromegaly and decreased of visual field which was getting worse since two weeks before(April11, 2011). He was consulted to ophthalmology and neurosurgery outpatient clinic. MRI with contrast revealed pituitary adenoma. Laboratories results showed TSHS:0.9773(0.35-4.94)uIU/ml, prolactin:0.51(4.04-15.2)ng/ml, testosterone less than 2.50(boys:13-17:28-1110)ng/ml, growth hormone was more than 40,00(>10.0)ng/ml. He was performed transsphenoidal removal cystic tumor. Pathological result showed macroscopic: yellowish cystous mass;0.6x0.4x0.2cm whether microscopic: appropiate to pituitary adenoma, non chromophobe. After surgery, patient was given DDAVP nasal spray 10 microgram/day, L-thyroxin 100 microgram once daily. One year after surgery, patient complaint of acromegaly, decreased visual field, especially in right and left temporal side, cephalgia. On physical examination, body weight was 91.5kg, height was184.5 cm. There was hemianopsia bitemporal. Tanner stage was A2P4G4. MRI with contrast showed pituritary adenoma relapse. Bone age was normal with height percentage based on it is about 96.8%. Tanner Whitehouse showed adult height 186.4cm. Thorax X ray showed heart and lungs were normal. Laboratories results revealed IGF1:1359(237-996)microgram/L, FT4:1(0.89-1.76)ng/dl; TSHS:0.3(0.5-4.94)microIU/ml(12-18yo), testosterone:435.1(28-1110) ng/dl. Working diagnosis was pituitary adenoma relapse post tumor resection, panhypopituitarism, diabetes insipidus. Testosterone 150mg once per month was added. Relapse of pituitary adenoma in children must be considered in the recurrence of clinical manifestations.

Clinical presentations and molecular characterization of Indonesian children with 5 alpha-reductase deficiency

Inactivating mutations in 5 alpha-reductase (SRD5A2) gene lead to steroid 5 alpha-reductase deficiency, a rare autosomal recessive condition affecting 46,XY individuals, who generally present with clinical spectrum ranging from a male phenotype with hypospadia to a female phenotype with normal wolffian structures. More than 50 different mutations responsible for this disorder have been documented. This study is to extend our previous report, which described two siblings with 2 novel mutations of SRD5A2 gene, on Indonesian children with 5 alpha-reductase deficiency. We describe clinical, hormonal, and molecular profiles of 14 children with 46,XY DSD and undervirilization due to 5-alpha reductase deficiency. DNAs extracted from peripheral blood lymphocytes, and the 5 exons of SRD5A2 gene were amplified using specific primers and sequenced. All of the patients (aged 2 months-18 years old) presented with genitalia ambiguity, including variable degree of hypospadia, phallic enlargement, palpable testis in ‘girls’, micropenis, cryptorchidism, virilization during puberty in ‘girls’ (8 out of 12 patients), and dismorphic appearances in 1 case. Twelve of them raised as girls, while eight patients who had entered pubertal age changed their identity to male. The T/DHT ratio were more than 20 in 8 patients with documented hormonal results. Three mutations including p.Gly34Fs, c.699-1 G>T, and p.Glu135Lys, which have not been reported in other populations were detected. The p.Arg227Gln was the most frequent mutations found (in 13/14 patients or 13/28 alleles). The combination of p.Val89Leu and p.Arg227Gln, which rarely reported in other populations, were detected in 6 patients. In our series, who all presented with genitalia ambiguity and mostly raised as girls, three mutations, including p.Gly34Fs, c.699-1 G>T, and p.Glu135Lys, which never been reported in other populations were detected.