The smallest dislocated microduplication of Xq27.1 harboring SOX3 gene associated with XX male phenotype.

OBJECTIVES: Approximately 90% of "XX males" are positive for SRY. However, there are isolated cases of sex reversal associated to other genes in male-determining pathway. CASE PRESENTATION: We describe a 1.3-old patient with 46,XX karyotype, male phenotypic gender and cryptorchidism. Microarray analysis revealed a de novo 273 kb duplication in the Xq27.1 region that contains SOX3. FISH with probe specific to SOX3 confirmed a unique genomic location of this duplication, dislocated proximal to the centromere of the X chromosome. CONCLUSIONS: This rare genetic condition was described in few other isolated cases that have associated SOX3 genetic rearrangements and DSD. Microarray and genome-wide-sequencing presents important part in routine diagnostics, and in delineation of other sex-determination-pathway genes in sex reversal disorders.

Is there a characteristic pattern of ambulatory blood pressure profile in type 1 diabetic children and adolescents?

PURPOSE: To examine the characteristics of ambulatory blood pressure (ABP) including blood pressure variability (BPV) and its association with albuminuria in type 1 diabetic (T1D) children and to identify potential predictors of high-normal albuminuria and microalbuminuria. METHODS: ABP monitoring was performed in 201 T1D children and adolescents (mean age, 14.7±3.8 years) with T1D duration over 1 year. The level of albuminuria was assessed as the albumin/creatinine ratio (ACR) and patients were further classified as low-normal, high-normal or microalbuminuria. RESULTS: Fifteen T1D children (7.5%) were hypertensive using office blood pressure (BP) and 10 (5%) according to ABP. T1D subjects had elevated 24-hour systolic BP (SBP) and diastolic BP (DBP) (+0.2 and + 0.3 standard deviation score [SDS]) and nighttime SBP and DBP (+0.6 and +0.8 SDS) compared to reference values. Patients with microalbuminuria had significantly higher 24-hour, daytime and nighttime DBP compared to normoalbuminuric subjects. There was a high percentage of nondippers (74.1%). Nighttime diastolic BPV was significantly higher in subjects with high-normal compared to low-normal albuminuria (p=0.01). A weak correlation was found between ACR and daytime DBP SDS (r=0.29, p<0.001 and nighttime DBP SDS (r=0.21, p=0.003). Age and nighttime diastolic BPV were predictors of high-normal albuminuria while nighttime DBP was a strong predictor for microalbuminuria. CONCLUSION: T1D children have impaired BP regulation although most of them do not fulfill the criteria for sustained hypertension. There is an association between diastolic ABP and diastolic BPV with rising levels of albuminuria pointing to a clear connection between BP and incipient diabetic nephropathy.

CONTINUOUS GLUCOSE MONITORING AND TYPE 1 DIABETES MELLITUS CONTROL IN CHILD, ADOLESCENT AND YOUNG ADULT POPULATION - ARGUMENTS FOR ITS USE AND EFFECTS.

Sensors for continuous glucose monitoring (CGM) in intercellular fluid are used as a contemporary method to achieve better control in type 1 diabetes mellitus (DM), which is best shown through lower glycated hemoglobin (HbA1c) levels.The aim of this study was to assess how many of our patients used CGM (parents were solely financing all the cost of the device) and what was the effect of CGM on the control of DM. Data were retrospectively collected from medical records of patients actively treated at the Division of Endocrinology, Diabetology, Pulmonology and Allergology, Department of Pediatrics, Sestre milosrdnice University Hospital Center. The t-test was used for independent samples to compare the mean levels of HbA1c before and after the inclusion of CGM. CGM was used by 81 (32.1%) of our patients with type 1 DM, of which 43 met the inclusion criteria. The mean HbA1c level 6 months before the introduction of CGM was 8.2%±1.9 and after 12 months of CGM use it was 7.4%±1.2, which was a statistically significant improvement (p=0.026). Furthermore, our results demonstrated that the greatest improvement in HbA1c level was recorded in the groups of young adults (18-25 years) and youngest children (<12 years). We confirmed the efficacy of CGM in achieving better control of type 1 DM by significantly improving HbA1c levels in a population of highly motivated patients.

Time to the Peak, Shape of the Curve and Combination of These Glucose Response Characteristics During Oral Glucose Tolerance Test as Indicators of Early Beta-cell Dysfunction in Obese Adolescents

Objective: Characteristics of the glucose response during oral glucose tolerance test (OGTT) may reflect differences in insulin secretion and action. The aim was to examine whether timing of the glucose peak, shape of the glucose curve and their combination could be indicators of beta-cell dysfunction in obese/severely obese adolescents with normal glucose tolerance (NGT). Methods: Data from 246 obese/severely obese adolescents who completed OGTT were reviewed. Out of 184 adolescents with NGT, 174 could be further classified into groups based on timing of the glucose peak (early/30 minutes vs late/≥60 minutes) and shape of the glucose curve (monophasic vs biphasic). Groups were compared with respect to insulin sensitivity (whole body insulin sensitivity index - WBISI), early-phase insulin secretion (insulinogenic index - IGI) and beta-cell function relative to insulin sensitivity (oral disposition index - oDI). Results: Late glucose peak (p=0.004) and monophasic glucose curve (p=0.001) were both associated with lower oDI after adjustment for age, sex, puberty stage and body mass index z-score. Among obese/severely obese adolescents with NGT, those with coexistent late glucose peak and monophasic glucose curve had lower oDI than those with early glucose peak and biphasic glucose curve (p=0.002). Moreover, a combination of late glucose peak and monophasic glucose curve was the most powerful predictor of the lowest oDI quartile [odds ratio (OR): 11.68, 95% confidence interval: 3.048-44.755, p<0.001]. Conclusion: Late timing of the glucose peak, monophasic shape of the glucose curve and, in particular, a combination of those characteristics during OGTT may indicate early beta-cell dysfunction in obese/severely obese adolescents with NGT.

Turner Syndrome: for successful treatment it is necessary to diagnose it early.

BACKGROUND: Turner Syndrome (TS) is a chromosomal disorder with short stature as the most common feature. The aim of this paper was to show the characteristics of TS patients treated at our Clinic, with an emphasis on their age at diagnosis and the effect of growth hormone therapy on their final height and height gain. METHODS: This retrospective study is based on the medical records of 37 female pediatric patients aged 0-18 years treated at the Pediatric Department of the Sestre Milosrdnice University Hospital Center from 1997 to 2017. RESULTS: Mean age at diagnosis is 7.55±5.13 years. In the observed period a trend towards later diagnosis was shown (P=0.004). Most patients (26) were treated with rhGH. The average height of all patients who reached their final height (N.=30) was 151.49±6.49 cm (standard deviation score [SDS]: -1.73±1.11). The initial height SDS was significantly lower in the treated compared to the untreated patients (P=0.02). The final height was 151.59±7.21 cm (SDS: -1.72±1.3) in the treated and 151.12±5.85 cm (SDS: -1.77±0.94) in the untreated patients. The difference between the initial and final height was significantly greater in the treated patients compared to the untreated patients (30.46 and 16.28 cm, P=0.039). The same was true for the difference between the initial and final height SDS (0.78, or -0.3, P=0.042). CONCLUSIONS: Based on the results of this research, TS is increasingly diagnosed at a later age. The effect of rhGH therapy was favorable and resulted in a greater height gain in the treated patients.

Blood pressure measurement methodology and technology in the SWEET diabetes centers: An international SWEET database survey.

INTRODUCTION: The accuracy of blood pressure (BP) measurement is a prerequisite for the reliable diagnosis and management of hypertension. OBJECTIVES: This survey evaluated the use of office and out-of-office BP measurements and the antihypertensive pharmacological treatment in expert pediatric diabetes centers. METHODS: A questionnaire was distributed in 78 reference pediatric diabetes centers of the SWEET international consortium. The methodology, devices, indications, and interpretation of office BP measurements (OBPM), 24-hour ambulatory BP monitoring (ABPM) and home BP monitoring (HBPM), and the preference for antihypertensive drug treatment was assessed. A grading score was developed to evaluate centers for overall BP measurement performance. RESULTS: Fifty-two centers responded. The average score for OBPM methodology was 72.5%, for technology 77.5% and the overall center score was 74.75%.The majority of the centers used appropriate methodology and technology, however, there was heterogeneity among them. Manual auscultatory or automated devices specifically validated for children were used by 26/52 centers. ABPM was recommended by 35/52 centers (27/35 had health insurance coverage) and HBPM by 18/52 centers. The BP measurement methodology and devices used for ABPM and HBPM were frequently inadequate. Angiotensin converting enzyme inhibitors were the most frequently prescribed drugs for treating hypertension. CONCLUSIONS: The majority of SWEET pediatric diabetes centers use adequate methodology and devices for BP measurement. ABPM is recommended by two thirds of the centers, whereas HBPM is less widely used. Further improvement in the quality of office and out-of-office BP measurements and harmonization among centers is necessary according to current guidelines.

Ambulatory blood pressure profile in office normotensive obese children: prevalence of masked hypertension and impact of parental hypertension.

Objectives The objectives of this study were to analyze ambulatory blood pressure (ABP) data in office normotensive obese children, to determine the prevalence and characteristics of masked hypertension (MH) and to investigate the impact of parental hypertension (PH) on ABP. Methods Seventy-nine obese and 35 normal weight children were enrolled. Each weight group was further divided in accordance with the presence of PH. ABP was recorded in an outpatient setting. Results Obese children had higher systolic ABP (p<0.05) and heart rate (p<0.001) compared with normal weight children. In obese children with PH, only nighttime systolic ABP (p=0.01) was higher compared with obese without PH, whereas normal weight children with PH had higher 24 h and daytime systolic and diastolic BP (all p<0.05) and nighttime DBP (p<0.001) compared with those without PH. PH but not obesity was associated with nondipping phenomenon. Prevalence of MH in the whole group was 23.6% being significantly higher in obese than in nonobese subjects (31.6 vs. 5.7%; p=0.0026) as well as in obese subjects with PH compared with obese subjects without PH (48.7 vs. 15%; χ2=10.37; p=0.001). MH was diagnosed more frequently in obese with high-normal office BP compared with obese with normal office BP, although it did not reach statistical significance (50 vs. 26.2%; χ2=3.631; p=0.056). In the normal weight group, neither PH nor office BP category had an impact on the prevalence of MH. Conclusions Office normotensive obese children had higher ABP values. MH was associated with obesity, PH and high-normal BP.

Persistent heterogeneity in diabetes technology reimbursement for children with type 1 diabetes: The SWEET perspective.

BACKGROUND: Frequent use of modern diabetes technologies increases the chance for optimal type 1 diabetes (T1D) control. Limited reimbursement influences the access of patients with T1D to these modalities and could worsen their prognosis. We aimed to describe the situation of reimbursement for insulins, glucometers, insulin pumps (CSII) and continuous glucose monitoring (CGM) for children with T1D in European countries participating in the SWEET Project and to compare data from EU countries with data from our previous study in 2009. METHODS: The study was conducted between March 2017 and August 2017. First, we approached diabetes technology companies with a survey to map the reimbursement of insulins and diabetic devices. The data collected from these companies were then validated by members of the SWEET consortium. RESULTS: We collected data from 29 European countries, whereas all types of insulins are mostly fully covered, heterogeneity was observed regarding the reimbursement of strips for glucometers (from 90 strips/month to no limit). CSII is readily available in 20 of 29 countries. Seven countries reported significant quota issues or obstacles for CSII prescription, and two countries had no CSII reimbursement. CGM is at least partially reimbursed in 17 of 29 countries. The comparison with the 2009 study showed an increasing availability of CSII and CGM across the EU. CONCLUSIONS: Although innovative diabetes technology is available, a large proportion of children with T1D still do not benefit from it due to its limited reimbursement.

Does Urinary Tract Ultrasound Have Its Place in the Treatment of Early Neonatal Jaundice? Neonatal Bilateral Adrenal Hemorrhage: Case Report.

Adrenal hemorrhage is a rare clinical entity in the neonatal period, with an incidence of 1.7-2.1/1000 births. It is more often diagnosed on the right side, whilst bilateral hemorrhage occurs in 10%-15% of cases. Clinical presentation shows a wide range of symptoms, from the signs of adrenal insufficiency to asymptomatic course of illness with incidental finding of changes on testing. Neonatal jaundice due to hemolysis of hemorrhagic content often is an accompanying sign. We present a male neonate born at term, with early neonatal jaundice of unknown cause and without evi-dence of perinatal infection. Ultrasound of the urinary tract revealed hypoechoic formations in the upper poles of both kidneys, confirmed by magnetic resonance imaging of the abdomen. Clinical and laboratory test results showed no signs of adrenal insufficiency. There was no confirmation of em-bryonic tumor or neuroblastoma. Ultrasound of the urinary tract as an available and noninvasive test has its place in the treatment of early neonatal jaundice of unknown cause. Additional invasive treat-ment and unnecessary laparotomy can be avoided with ultrasound monitoring of the formation re-gression.

EFFECT OF GROWTH HORMONE THERAPY IN CHILDREN WITH PRADER-WILLI SYNDROME - OUR FIRST EXPERIENCES.

- Prader-Willi syndrome (PWS) is the most common cause of morbid obesity in childhood. It is the consequence of the lack of expression of genes on the paternally inherited 15q11.2-q13 region. Hyperphagia, obesity, short stature, psychomotor retardation and deterioration of behavior predominate in clinical presentation. Recombinant human growth hormone (rhGH) therapy, along with restriction of caloric intake, has become the mainstay in the management of PWS patients. Anthropometric parameters (height, body mass index (BMI)), therapy effect on carbohydrate and lipid metabolism, and occurrence of side effects were monitored in four children with PWS treated with rhGH for ≥2 years at doses of up to 1 mg/m2/day. During the follow-up, the height standard deviation score (SDS) increased in comparison with baseline values, and after ≥2 years of treatment with rhGH it was within the reference range for the general children population. BMI SDS decreased after the first year of treatment, but thereafter increased again; still, the level of BMI SDS was much better in comparison with most children with PWS of the same age and gender. RhGH therapy had no negative effect on glucose and lipid metabolism, nor caused any other adverse effect. Therapy including a customized diet for PWS, along with rhGH therapy, provided a satisfactory growth rate and prevented development of morbid obesity without side effects. This treatment approach would ensure transition of a greater number of PWS patients into adult care, where the multidisciplinary approach in care should be continued.

Medical Emergencies in Pediatric Dentistry.

Medical emergencies that are life threatening can occur in dental practice. Complications may arise because of an underlying disease or a reaction to medication. Reactions to medications may be allergic and toxic. The most common reactions are toxic reactions to local anesthetics, whereas allergies occur mainly as a consequence of the application of antibiotics, usually penicillin. In response to stress, vasovagal syncope typically occurs. Other causes may be related to an underlying disease-specific pathology (such as acute asthma attack, diabetic ketoacidosis, hypoglycemia, or seizures) or accidents (aspiration of a foreign body causing obstruction of the respiratory system). For all the above conditions, guidelines have been established that need to be known. If complications occur or necessary measures are not taken, it can lead to cardiac and respiratory arrest. Therefore, cardiopulmonary resuscitation is needed. All procedures and dosages should be adapted to the age of the child.

Genesis of two most prevalent PROP1 gene variants causing combined pituitary hormone deficiency in 21 populations.

Two variants (c.[301_302delAG];[301_302delAG] and c.[150delA];[150delA]) in the PROP1 gene are the most common genetic causes of recessively inherited combined pituitary hormones deficiency (CPHD). Our objective was to analyze in detail the origin of the two most prevalent variants. In the multicentric study were included 237 patients with CPHD and their 15 relatives carrying c.[301_302delAG];[301_302delAG] or c.[150delA];[150delA] or c.[301_302delAG];[ 150delA]. They originated from 21 different countries worldwide. We genotyped 21 single-nucleotide variant markers flanking the 9.6-Mb region around the PROP1 gene that are not in mutual linkage disequilibrium in the general populations--a finding of a common haplotype would be indicative of ancestral origin of the variant. Haplotypes were reconstructed by Phase and Haploview software, and the variant age was estimated using an allelic association method. We demonstrated the ancestral origin of both variants--c.[301_302delAG] was carried on 0.2 Mb-long haplotype in a majority of European patients arising ~101 generations ago (confidence interval 90.1-116.4). Patients from the Iberian Peninsula displayed a different haplotype, which was estimated to have emerged 23.3 (20.1-29.1) generations ago. Subsequently, the data indicated that both the haplotypes were transmitted to Latin American patients ~13.8 (12.2-17.0) and 16.4 (14.4-20.1) generations ago, respectively. The c.[150delA] variant that was carried on a haplotype spanning about 0.3 Mb was estimated to appear 43.7 (38.4-52.7) generations ago. We present strong evidence that the most frequent variants in the PROP1 gene are not a consequence of variant hot spots as previously assumed, but are founder variants.

Incidence of type 1 diabetes mellitus in 0 to 14-yr-old children in Croatia--2004 to 2012 study.

BACKGROUND: The incidence of type 1 diabetes mellitus (T1DM) among children and adolescents increased during the last 50 yr. The T1DM incidence in Croatia was 8.87/100.000/yr over 1995-2003, with an annual increase of 9%, which placed Croatia among countries with moderate risk for T1DM. AIM: To investigate incidence rates and trends of T1DM from 2004 to 2012 in 0 to 14-yr-old Croatian children, and to compare the results with previous studies in Croatia and other European countries. METHODS: T1DM crude incidence rates are estimated for the entire group and three subgroups: 0-4, 5-9, and 10-14 yr. Standardized incidence is calculated using the method of direct standardization according to World Health Organization (WHO) standard world population. The incidence rates by gender, age groups, seasonality, and calendar year, and their interactions were analyzed using Poisson regression model. RESULTS: A total of 1066 cases were ascertained over 2004-2012. The standardized incidence was 17.23/100.000/yr (95% CI: 16.19-18.26), with no significant differences in incidence rates or trends between boys and girls. Statistically significant annual increase of 5.87% (p < 0.001) was found for the whole group, and for the subgroups 5-9 yr (6.82%; p < 0.001) and 10-14 yr (7.47%; p < 0.001). In the youngest subgroup (0-4 yr), annual increase was lower (2.43%; p = 0338) and not statistically significant. CONCLUSION: The incidence of childhood T1DM is increasing in Croatia, thus placing Croatia among countries with high risk for T1DM. The annual increment of 5.87% is considerably lower than 9.0% reported earlier, but still higher than the European average (3.9%). The increase in incidence ceased in youngest children.

IL12RB2 gene is associated with the age of type 1 diabetes onset in Croatian family Trios.

BACKGROUND: Common complex diseases are influenced by both genetic and environmental factors. Many genetic factors overlap between various autoimmune diseases. The aim of the present study is to determine whether four genetic variants known to be risk variants for several autoimmune diseases could be associated with an increased susceptibility to type 1 diabetes mellitus. METHODS AND FINDINGS: We genotyped four genetic variants (rs2358817, rs1049550, rs6679356, rs9865818) within VTCN1, ANXA11, IL12RB2 and LPP genes respectively, in 265 T1DM family trios in Croatian population. We did not detect association of these polymorphisms with T1DM. However, quantitative transmission disequilibrium test (QTDT, orthogonal model) revealed a significant association between the age of onset of T1DM and IL12RB2 rs6679356 variant. An earlier onset of T1DM was associated with the rs6679356 minor dominant allele C (p = 0.005). The association remained significant even after the Bonferroni correction for multiple testing and permutation. CONCLUSIONS: Variants originally associated with juvenile idiopathic arthritis (VTCN1 gene), sarcoidosis (ANXA11 gene), primary biliary cirrhosis (IL12RB2 gene) and celiac disease (LPP gene) were not associated with type 1 diabetes in our dataset. Nevertheless, association of IL12RB2 rs6679356 polymorphism with the age of T1DM onset suggests that this gene plays a role in defining the time of disease onset.

Regional differences in incidence and clinical presentation of type 1 diabetes in children aged under 15 years in Croatia.

AIM: To determine regional differences in the incidence, incidence trends, and clinical presentation of type 1 diabetes in children under the age of 15 years in Croatia in a 9-year period (1995-2003). METHODS: We included the patients who had been diagnosed with the disease and had started the insulin treatment before they were 15 years old. Regional differences between eastern, central, and southern Croatia were observed. The gross incidence was expressed by the number of newly diagnosed type 1 diabetes patients in 100000 children of the same age and sex per year, ie, for the 0-14 age group, and for the 0-4, 5-9, and 10-14 subgroups. RESULTS: The highest incidence was observed in southern Croatia (10.91 per 100000/y) and the lowest in central Croatia (8.64 per 100000/y), and in eastern Croatia the incidence was 8.93 per 100000/y. All three regions showed a growing incidence trend, which was significant only in eastern and southern Croatia. There was 35.9% of patients with diabetic ketoacidosis in eastern Croatia, 41.7% in central Croatia, and 31.28% in southern Croatia. CONCLUSION: Croatian regions show differences in the incidence, incidence trends, and disease presentation of type 1 diabetes. A further follow-up is needed to establish whether the regional differences are a consequence of the population dynamics in the observed period or they will continue to exist, pointing to differences in environmental risk factors.

Clinical characteristics at presentation of type 1 diabetes mellitus in children younger than 15 years in Croatia.

The aim of the study was to determine the clinical and biochemical characteristics of type 1 diabetes mellitus (DM) at presentation in children younger than 15 years in Croatia during a 9-year period, with special attention to diabetic ketoacidosis (DKA) incidence. The registered data set comprised blood glucose, pH, serum bicarbonate levels, and clinical symptoms at disease manifestation. During the study period, 692 children were diagnosed with type 1 DM. Polydipsia (96.7%), polyuria (96.05%), and weight loss (82.7%) were the most frequent symptoms anticipating disease detection. Enuresis was recorded in 11.55%. A total of 36.41% patients had DKA (pH < 7.3) at disease onset. During the 9-year period, the percentage of children presenting with DKA at time of diagnosis decreased from 41.67% to 33.33% (z = 1.68, p = 0.046). A positive family history of DM, the only factor with an impact on the DKA incidence rate in our population, lowers the probability of the development of ketoacidosis. This study confirms the importance of the detection of the classic symptoms of polyuria, polydipsia, and weight loss in patients with new-onset type 1 DM. The percentage of patients with DKA at diabetes onset decreased during the observed period but is still high and includes one-third of all patients. This is why in every acutely ill child, especially at a younger age, one should evaluate the possibility of type 1 DM to avoid the development of ketoacidosis.

Classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency in croatia between 1995 and 2006.

AIMS: To evaluate the incidence, gender, symptoms and age at diagnosis among patients with classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency in Croatia. METHODS: Data were collected retrospectively for all classical CAH patients born or electively aborted following prenatal diagnosis between 01.01.1995 and 31.12.2006 and were compared with the data of the previously conducted study evaluating CAH patients discovered between 1964 and 1984. RESULTS: During a 12-year period, 34 classical CAH patients were born. There were 20 salt-wasting (SW) (12 females/8 males) and 14 simple virilizing (SV) patients (7 females/7 males). If 3 female fetuses, electively aborted, were added, that would be a total of 37 CAH patients. With 532,942 live births and 34 CAH patients born over this period, incidence of classical CAH was estimated to 1:15,574 or 1:14,403 if 3 electively aborted fetuses were included. The lower incidence of SW boys compared to SW girls (8:12) and similar number of SW and SV boys (8:7) indicate that substantial proportion of SW boys die unrecognized. Owing to better health care, diagnosis was established significantly earlier in SW and SV girls compared to the period of 1964-1984 (p < 0.003). During 1995-2006, none of the patients died following the diagnosis of CAH, and there was no erroneous sex assignment. CONCLUSION: Despite of improvement in health care, diagnosis of CAH in Croatia is still delayed and some of the patients go unrecognized or die. Therefore, we think that the results of our study support the need for the introduction of newborn screening.

Classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency in Croatia between 1995 and 2006.

AIMS: To evaluate the incidence, gender, symptoms and age at diagnosis of patients with classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency in Croatia. METHODS: Data were collected retrospectively for all classical CAH patients born or electively aborted following prenatal diagnosis between January 1, 1995 and December 31, 2006 and were compared with the data of a previously conducted study evaluating CAH patients discovered between 1964 and 1984. RESULTS: During a 12-year period 34 classical CAH patients were born. There were 20 salt-wasting (SW; 12 female/8 male) and 14 simple-virilizing (SV; 7 female/7 male) patients. If 3 female, electively aborted fetuses were added, there would be a total of 37 CAH patients. With 532,942 live births and 34 CAH patients born over this period, the incidence of classical CAH was estimated at 1:15,574 or 1:14,403 if the 3 electively aborted fetuses were included. The lower incidence of SW boys compared to SW girls (8:12) and similar number of SW and SV boys (8:7) indicate that a substantial proportion of SW boys die unrecognized. Owing to better healthcare, the diagnosis was established significantly earlier in SW and SV girls compared to the period of 1964-1984 (p < 0.003). During 1995-2006, none of the patients died following the diagnosis of CAH and there was no erroneous sex assignment. CONCLUSION: Despite improvements in healthcare, the diagnosis of CAH in Croatia is still delayed and some of the patients go unrecognized or die. Therefore, the results of our study support the need to introduce newborn screening.