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Gender cckange anrd

stigmatizatian trn ilate-'tre ate d [ ffi dsnesi a n cki ld ren,adalescent, and adult patientswitk DSts

A\lNASllASlA EDlATl. Indonesia

1430 so SYMP0SIA: Fl01l TOPICS Auditorium 2. Ground FloorChains: lVIicheile .Jac[< & ByunE-Kuy Suh

X430 Disseeting eangenital hypothyraidism by next generation sequencingSAT0SHil NARlJlVll, Japan

1 500 lnsights into the diagnosis and management of cangenitatltypothyroidismPA[.j[_ hl0FMAN, New Zealand

I 53CI fitosing Oerennony Auditoriunn 2, Grnund Floor

-PRACTICAL STREAM

The practical stream is a series of concurrent sessions that are designed to be mare interactive, hands 0n style sessi}ns. The topics covered inthis stream are designed for atrlied health staff such as educators, nurses, social workers, dietitians and also general paediatricians.

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1 lnstitute of Endocrinology and Diabetes, The Children'sHospital Westmead

2 Discipline of Paediatrics and Child Health, lJniversity olSydney

Turner syndrome (TS) and related sex chromosomeabnormalities are associated with a variety of karyotypesand phenotypes affecting 1 in 2500 live births, Mosaicismwith Y material (45,X46,XY) and female phenotype is rare(<1 in 15 000 births)(1). Their risk of gonadal malignancyis 10-15%, and up to 50% in those with ambiguousphenotype at birth(2). The SHOX gene is located on bothX and Y chromosomes but is more prone to deletions onthe X chromosome, potentially influencing height outcomesacross TS karyotypes(3). However, children with SHOXdeficiency respond similarly to TS girls when treated withthe same dose of growth hormone (GHX4). We thereforeexamined height outcomes and gonadal malignancy rates inTS vs 45,)V46,XY females.

We identified 198 females aged < 30 years with TS or mixedgonadal dysgenesis treated with GH (underTS or auxologicalcriteria). Final height (FH) was available on 51 TS (45,X ormosaic without Y material) females. An additional 13 had45,X146,XY karyotype with TS phenotype, and two had non-mosaic 46,XY karyotypes with cytogenetic abnormalitiesconsistent with TS. Of these 15 females, gonadal tissuehistology was available for 11 and FH in nine. We evaluatedpatient records for age, height, mid-parental height (MPH),GH dose at commencement, duration of therapy and growthresponse at 12 months and at FH. Comparisons betweenTS and 45,W46,XY groups were performed using the Mann-Whitney U test.

All 45,X46,XY patients had a female phenotype and fivehad clitoromegaly at birth. Three were identified prenatally;age at diagnosis ranged from birth to 13 years, with themost common presenting features being short stature (n=5),ambiguous genitalia (n=5) and dysmorphic features (n=2).Of the 11 that underwent gonadectomy, four (none virilised atbirth) had a gonadoblastoma, including one dysgerminomain situ.

Age, height, MPH,GH dose at commencement, durationof therapy and height z-score afler' 12 months did notdiffer between groups. Median FH z-score for 45,X46,XYwas higher than TS, -1.12 [range ;1.96,0.31], vs -1.59[-3.12,0.01], P=0.016. Response to GH therapy (median Aheight z-score) after 12 months was similar: 0.45 [-0.04,0.84]vs 0.39 l-0.21 ,1.141, p=a.61 . However, height response overthe total duration of therapy was better for 45,X46XY: 1.510.72,2.881 vs 0.87 [-0.e8,2. 1 4], p=0.009.

45,W46,XY females appear to respond differently to GHtherapy, suggesting a possible contribution ol SHOX onthe Y chromosome. The rate of germ cell tumours in non-virilised females (36%) is higher than previously reported.

References:

1. Johansen ML, Hagen CP, Rajpert-De Meyts E et al.45,W46,XY Mosaicism: Phenotypic Characteristics,Growth, and Reproductive Function - a RetrospectiveLongitudinal Study. J Clin Endocrin Metab 2012:97(8):E1 540-1 54e.

2. Cools M, Pleskacova J, Stoop H, et al. Gonadal Pathologyand Tumor Risk in Relation to Clinical Characteristics inPatients with 45,X46,XY Mosaicism. J Clin EndocrinMerab 2011 ; 96(7): E1171-E1180.

3. Oliveira CS, Alves C. The role of the SHOX gene in thepathophysiology of Turner syndrome. Endocrinol Nutr2011;58(8): 433-442.

4. Blum WF, Ross JL, Zimmermann AG et al. GH Treatmentto Final Height Produces Similar Height Gains in Patientswith SHOX Deficiency and Turner Syndrome: Results ofa Multicenter Trial. J Clin Endocrin Metab 2013; 98(8):E1 383-1 392.

oR06.04

CLINICAL AND MUTATIONAL SPECTRUMOF PATIENTS WITH CONGENITAL LIPOIDADRENAL HYPERPLASIA IN SOUTHEASTASIAAriyawatkul. Kansudal, Jaruratanasirikul Somchit2,Loke, Kah Yin3, Nakavachara, Pairunyara, Kongkanka,Chawkaews, Sahakitrungruang, Tanineel.I Department of Pediatrics, Faculty of Medicine,

Chulalongkorn University, Bangkok, Thailand, 1 03302 Department of Pediatrics, Prince of Songkla University,

Songkhla, Thailand3 Department of Pediatrics, KTP- National University

Children's Medical lnstitute, National University Hospital,Singapore

4 Department of Pediatrics, Faculty of Medicine SirirajHospital, Mahidol University, Bangkok, Thailand

5 Queen Sirikit National lnstitute of Child Health, BangkoliThailand

*Corresponding Author (Taninee. P@chula.ac.th)

Aims: Mutations in Steroidogenic Acute Regulatory protein(SIAR) cause congenital lipoid adrenal hyperplasia (lipoirlCAH), characterized by absent steroidogenesis, potentiallylethal salt loss, 46,XY sex reversal and massively enlargedadrenals engorged with cholesterol esters. Nonclassic lipoidCAH is a recently recognized disorder caused by SA FImutations that retain partial function. We aim to delineatethe clinical and mutational spectrum of SiAR mutations inpatients with lipoid CAH.

Methods: The entire coding regions of the SIAF gene wereassessed by polymerase chain reaclion and sequencinganalysis.

Results: There were 10 patients of lipoid CAH had mutationsin the SIAR gene with 5 novel mutations (p.P230b!{fsX,lVS6-1G>A, lVS3+(2-3)insT, p.W147R, p.Q264R). EiShtpatients had classic lipoid CAH presenting with adrenalcrisisduring early infancy (range of onset 3-11 months ol age).Two siblings had nonclassic phenotypes with later onsetadrenal insufficiency without disordered sex development.Adrenal enlargement by imaging was demonstrated in only3 cases of classic lipoid CAH. The functional studies of novelSIAR mutations are being under investigation.

Conclusion: SIAF mutations may not be rare in SoutheastAsian population. There is a broad clinical spectrum of StAFmutations varying from early onset adrenal insufficiency tolate onset of glucocorticoid deficiency with only mild defectsin mineralocorticoid and sex steroid synthesis. Adrenalgland enlargement is not pathognomonic for lipoid CAH.

oR06.05

GENDER CHANGE AND STIGMATIZATIONIN LATE-TREATED INDONESIAN CHILDREN,ADOLESCENT, AND ADULT PATIENTS WITHDSDEdiati. Annastasiar-z, Juniarto, Achmad Zulla2,Birnie, Erwin3,'Okkerse, Jolanda4, de la Croix, Anne4,Wisniewski, Amys,Drop, Stenvert4, Faradz, Sultana MH2,Dessens, Arianne4

1 Diponegoro University, Facutty of psychology, Semarang,Indonesia

2 Diponegoro University, Faculty of Medicine, Center forBiomedical Research (CEB\OR), Indonesia3 Era1ytus University Rotterdam - Institute of Heatth policyand Management, the Netherlands

4 Sophia Children's Hospitat - ErasmusMC Rotterdam, theNetherlands

5 University of Oktahoma Heatth Sciences Center,Oklahoma, United States

ln lndonesia clinical management ol DSD is challengedby limited knowledge and limited diagnostic and treatmentfacilities. Prior to this study, most patients remainedunlreated and grew up with ambiguous bodies and doubtsabout their gender. We investigated patients'experiences ofbeing raised in ambiguity.

ll8lndonesian patients, ages 6-41, with 46XX DSD (n=27),46XY DSD (n=77) and chromosomat DSD (n=14) werecompared to 118 control subjects matched for gendel age,and living area. Questionnaires for gender identity, genderrole behavior and social stigmatization were translated ordesigned. The psychometric properties were satisfactory.For patient and control group comparisons, Mann-WhitneyU and Fisher's Exact tests were applied.

The results showed thal 7"k of the children, g% of theadolescents and 44y" of the adults changed gender,particularly non-diagnosed and non-treated patients withzl6XY DSD (81ol.). 95% of the patients changed genderfrom female to male, including untreated patients with46)0( CAH-SV. Compared to control groups, cross_genderrole behavior was seen in young girls with 46XX CAH-SV(F.044 ard adolescent girls with different types of DSD(F.01). ln girls with DSD, conf usion with gender identity wasseen (young girls p=.994; adolescent girts p=.01). Aduti menrepgded past cross-gender role behavior (p=.01) and pastproblems in gender identilication (p=.01) prior to female-to_male gender change.

ChiHren with genital ambiguity (p<.006) and cross genderbehavior (p<0.001) and adults with ambiguous bodies(p=.001) and adutts who changed gender (p<b.OS) sufferedstigmatization. Rejection or isolation elicited depression andwithdrawalfrom social activities in girls (p=.002) and women(p=.009) and youngsters who had changed genler (p=.02).We contyde that high percentage of our patiehb chhngedgende.r. The wjsh for gender change was'particularty sEenin patients with progressive masculinizatidn. patienis withDSD who had visible ambiguity in physical and behavioralappearance suffered stigmatization. Teasing and rejectionled.to strong emotional reactions. Early clin'ical evaiuationand. treatment, patierrt and parent eduiation, and teachingcoping strategies will improve quality of life.