ACTION Teens Saudi Arabia: Perceptions, attitudes, motivators, and barriers among adolescents living with obesity, caregivers, and healthcare professionals in Saudi Arabia.

Obesity is predicted to affect approximately one-quarter of children/adolescents in Saudi Arabia by 2030, but there is limited evidence regarding the perceptions, attitudes, behaviours, and barriers to effective obesity care for adolescents living with obesity (ALwO), caregivers of ALwO, and healthcare professionals (HCPs). We report data from 500 ALwO (aged 12-<18 years), 500 caregivers, and 200 HCPs surveyed in Saudi Arabia as part of the global, cross-sectional ACTION Teens study (NCT05013359). Nearly all respondents recognized that obesity has a strong impact on overall health (ALwO 88%; caregivers 85%; HCPs 90%). Most ALwO and caregivers were aware of the ALwO's obesity status (95% and 99%, respectively) and worried about weight impacting the ALwO's future health (both ≥99%), and social media was their most commonly used source of weight-management information (60% and 53%, respectively). Among ALwO and caregivers who had discussed weight with an HCP in the past year, most experienced ≥1 negative feeling following their most recent discussion (61% and 59%, respectively). Although 81% of HCPs felt motivated to help their ALwO patients lose weight, 57% believed weight loss was completely the ALwO's responsibility (compared with only 37% of ALwO and 35% of caregivers). This may reflect the finding that only 24% of HCPs had received advanced training in obesity/weight management after medical school. Overall, while respondents had similar perceptions of the impact of obesity, we found HCPs' attitudes towards weight loss were not aligned with those of ALwO and caregivers, suggesting a need for improved communication and obesity education.

Information needs on type 1 diabetes mellitus (T1DM) and its management in children and adolescents: a qualitative study.

OBJECTIVE: The objective of this study is to explore the information needs related to insulin therapy in children and adolescents with type 1 diabetes mellitus (T1DM) from the children's perspectives as well as their caregivers. DESIGN: Qualitative study; semistructured interviews. To identify emerging themes relating to information needs, open coding and thematic analysis were employed. SETTING: Participants were recruited from a tertiary care children's hospital in Kuala Lumpur, Malaysia and a specialist hospital in Riyadh, Saudi Arabia. PARTICIPANTS: Thirty one children with a mean age of 11.5 years (SD=1.9) and their caregivers were interviewed. Seventeen participants were from Malaysia and 14 were from Saudi Arabia. RESULTS: Four themes of information emerged from the interviews, including information related to (1) hypoglycaemia and hyperglycaemia, (2) insulin therapy, (3) injection technique and (4) other information needs pertaining to continuous glucose monitoring, access to peer groups and future advances in insulin therapy. CONCLUSION: This study provided valuable insights into the information needs related to T1DM and insulin therapy among children and adolescents with T1DM that should be considered by stakeholders in the development of age-appropriate education materials. Such materials will assist children and adolescents to better manage their life-long T1DM condition from adolescence until adulthood.

Isolated Pancreatic Agenesis Secondary to PTF1A Gene Mutation: A Case Series and Literature Review.

Background Neonatal diabetes mellitus is a rare form of monogenic diabetes which is diagnosed in the first six months of life. It is often related to genetic mutations; hence, genetic testing is warranted. Here, we present six cases of pancreatic agenesis resulting in neonatal diabetes with PTF1A gene mutation. Methodology This retrospective case series study included six pediatric cases of neonatal diabetes mellitus who are currently following at pediatric endocrinology clinics at King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. Results The study reported six patients with a mean age of eight years who presented with pancreatic agenesis resulting in neonatal diabetes with PTF1A gene mutation. In four patients, there was no evidence of cerebellar agenesis. Conclusions Neonatal diabetes is a challenging disease that must be diagnosed early to prevent subsequent metabolic complications. Genetic testing is recommended in neonates who present with prolonged duration of hyperglycemia. Insulin replacement is the treatment of choice.

The views of teenagers with obesity, their caregivers, and doctors: a plain language summary of the ACTION Teens global survey.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of a research survey called ACTION Teens. In our survey, 12,987 people from 10 countries answered questions about obesity. They were: 5275 teenagers with obesity, 5389 caregivers of teenagers with obesity, and 2323 doctors who provide medical care for teenagers with obesity. WHAT WERE THE MAIN RESULTS OF THE SURVEY?: Most teenagers with obesity were worried about their weight and thought that losing weight was their responsibility. Many teenagers had already tried to lose weight. For teenagers, wanting to be more fit or in better shape was the top reason for wanting to lose weight. Some caregivers did not realize how worried their teenager was about their own weight. There were also some caregivers who were not aware of their teenager's recent attempts to lose weight. As a group, the doctors did not know the main reasons why teenagers want to lose weight. They also did not know the main reasons preventing teenagers from losing weight. WHAT DO THE RESULTS OF THE SURVEY MEAN?: Teenagers with obesity will be better supported and understood if there is better communication between teenagers, caregivers, and doctors. Clinical Trial Registration: NCT05013359 (ClinicalTrials.gov).

Experiences and needs of Saudi mothers when a child or adolescent is diagnosed with type 1 diabetes mellitus: a qualitative study.

AIM: To explore the experiences of Saudi mothers with children or adolescents who have Type 1 diabetes mellitus at time of diagnosis. BACKGROUND: The Kingdom of Saudi Arabia (KSA) has one of the highest incidence rates of Type 1 diabetes mellitus in children and adolescents in the world. Few studies have considered the most appropriate methods of support for parents in the KSA and none report the experiences of Saudi mothers. DESIGN: Phenomenological inquiry. METHOD: Qualitative interviews were conducted with 11 Saudi mothers and data were analysed following Giorgi's 5-step method. RESULTS: The lived experiences of Saudi mothers coalesced around three overarching themes and eight subthemes: 1. In the dark (mother's instinct, challenges of diagnosis phase, cultural reflections); 2. Empowerment (methods of support, mother's health and wellbeing); 3. Coping and acceptance (stigma and cultural perceptions, coping strategies, transformation and adaptation). CONCLUSIONS: Effective interventions delivered in other countries to support mothers may be effective in the KSA. However, the central role that Saudi mothers play in the management of their child's condition, and the place of Islam in Saudi society, indicate the need for customized methods of support that take into account psychosociocultural needs of both mother and child.

Misalignment among adolescents living with obesity, caregivers, and healthcare professionals: ACTION Teens global survey study.

BACKGROUND: There is limited evidence regarding the experiences, challenges, and needs of adolescents living with obesity (ALwO), their caregivers, and healthcare professionals (HCPs). OBJECTIVES: The cross-sectional, survey-based global ACTION Teens study aimed to identify perceptions, attitudes, behaviours, and barriers to effective obesity care among ALwO, caregivers of ALwO, and HCPs. METHODS: ALwO (aged 12 to <18 years; N = 5275), caregivers (N = 5389), and HCPs treating ALwO (N = 2323) from 10 countries completed an online survey (August-December 2021). RESULTS: Most ALwO perceived their weight as above normal (76% vs. 66% of caregivers), were worried about its impact on their health (85% vs. 80% of caregivers), and recently made a weight loss attempt (58%). While 45% of caregivers believed ALwO would slim down with age, only 24% of HCPs agreed. Most commonly reported weight loss motivators for ALwO were wanting to be more fit/in better shape according to ALwO (40%) and caregivers (32%), and improved confidence/social life according to HCPs (69%). ALwO weight loss barriers included lack of hunger control (most commonly reported by ALwO/caregivers), lack of motivation, unhealthy eating habits (most commonly agreed by HCPs), and lack of exercise. CONCLUSIONS: Misalignment between ALwO, caregivers, and HCPs-including caregivers' underestimation of the impact of obesity on ALwO and HCPs' misperception of key motivators/barriers for weight loss-suggests a need for improved communication and education.

Digital Health for Supporting Precision Medicine in Pediatric Endocrine Disorders: Opportunities for Improved Patient Care.

Digitalization of healthcare delivery is rapidly fostering development of precision medicine. Multiple digital technologies, known as telehealth or eHealth tools, are guiding individualized diagnosis and treatment for patients, and can contribute significantly to the objectives of precision medicine. From a basis of "one-size-fits-all" healthcare, precision medicine provides a paradigm shift to deliver a more nuanced and personalized approach. Genomic medicine utilizing new technologies can provide precision analysis of causative mutations, with personalized understanding of mechanisms and effective therapy. Education is fundamental to the telehealth process, with artificial intelligence (AI) enhancing learning for healthcare professionals and empowering patients to contribute to their care. The Gulf Cooperation Council (GCC) region is rapidly implementing telehealth strategies at all levels and a workshop was convened to discuss aspirations of precision medicine in the context of pediatric endocrinology, including diabetes and growth disorders, with this paper based on those discussions. GCC regional investment in AI, bioinformatics and genomic medicine, is rapidly providing healthcare benefits. However, embracing precision medicine is presenting some major new design, installation and skills challenges. Genomic medicine is enabling precision and personalization of diagnosis and therapy of endocrine conditions. Digital education and communication tools in the field of endocrinology include chatbots, interactive robots and augmented reality. Obesity and diabetes are a major challenge in the GCC region and eHealth tools are increasingly being used for management of care. With regard to growth failure, digital technologies for growth hormone (GH) administration are being shown to enhance adherence and response outcomes. While technical innovations become more affordable with increasing adoption, we should be aware of sustainability, design and implementation costs, training of HCPs and prediction of overall healthcare benefits, which are essential for precision medicine to develop and for its objectives to be achieved.

25-Hydroxylase vitamin D deficiency in 27 Saudi Arabian subjects: a clinical and molecular report on CYP2R1 mutations.

Vitamin D deficiency remains a major cause of rickets worldwide. Nutritional factors are the major cause and less commonly, inheritance causes. Recently, CYP2R1 has been reported as a major factor for 25-hydroxylation contributing to the inherited forms of vitamin D deficiency. We conducted a prospective cohort study at King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia, to review cases with 25-hydroxylase deficiency and describe their clinical, biochemical, and molecular genetic features. We analyzed 27 patients from nine different families who presented with low 25-OH vitamin D and not responding to usual treatment. Genetic testing identified two mutations: c.367+1G>A (12/27 patients) and c.768dupT (15/27 patients), where 18 patients were homozygous for their identified mutation and 9 patients were heterozygous. Both groups had similar clinical manifestations ranging in severity, but none of the patients with the heterozygous mutation had hypocalcemic manifestations. Thirteen out of 18 homozygous patients and all the heterozygous patients responded to high doses of vitamin D treatment, but they regressed after decreasing the dose, requiring lifelong therapy. Five out of 18 homozygous patients required calcitriol to improve their biochemical data, whereas none of the heterozygous patients and patients who carried the c.367+1G>A mutation required calcitriol treatment. To date, this is the largest cohort series analyzing CYP2R1-related 25-hydroxylase deficiency worldwide, supporting its major role in 25-hydroxylation of vitamin D. It is suggested that a higher percentage of CYP2R1 mutations might be found in the Saudi population. We believe that our study will help in the diagnosis, treatment, and prevention of similar cases in the future.

Achieving Optimal Short- and Long-term Responses to Paediatric Growth Hormone Therapy

It is over sixty years since the first administration of human growth hormone (GH) to children with GH deficiency, and over thirty years since recombinant human GH has been available for treatment of GH deficiency and a wider range of non-GH deficiency disorders. From a diagnostic perspective, genetic analysis, using single gene or Sanger sequencing and more recently next generation or whole exome sequencing, has brought advances in the diagnosis of specific causes of short stature, which has enabled therapy to be targeted more accurately. Genetic discoveries have ranged from defects of pituitary development and GH action to abnormalities in intracellular mechanisms, paracrine regulation and cartilage matrix formation. The strategy of GH therapy using standard doses has evolved to individualised GH dosing, depending on diagnosis and predictors of growth response. Evidence of efficacy of GH in GH deficiency, Turner syndrome and short children born small for gestational age is reviewed. The importance of critical assessment of growth response is discussed, together with the recognition and management of a poor or unsatisfactory growth response and the organisational issues related to prevention, detection and intervention regarding suboptimal adherence to GH therapy.

Molecular genetics and phenotype/genotype correlation of 5-α reductase deficiency in a highly consanguineous population.

CONTEXT AND OBJECTIVES: 5-α reductase deficiency is a rare 46,XY disorder of sex development. We present detailed phenotypic and genotypic features of a cohort of 24 subjects from a highly consanguineous population of Saudi Arabia SUBJECTS AND METHODS: We studied the clinical presentation and hormonal profiles of 24 subjects diagnosed with 5-α reductase deficiency and performed genetic testing on DNA isolated from their peripheral blood using polymerase chain reaction and direct sequencing of the SRD5A2. RESULTS: All subjects had 46,XY karyotype and presented with atypical appearance of external genitalia ranging from clitoromegaly, micophallus with hypospadias, undescended testes to completely normally looking female genitalia. Thirteen (54%) of them had severe under virilization and were assigned female sex at birth. The other 11 subjects were raised as males. Stimulated Testosterone:Dihydrotestosterone ratio was high in all 16 subjects in whom it was measured. The genetic testing revealed 2 nonsense mutations (p.R103X and p.R227X) in 2 unrelated subjects, 3 missense mutations (p.P181L, p.A228T, p.R246Q) in 11 subjects and a splice site mutation (IVS1-2A > G) in 11 other subjects. There was significant phenotypic variability even in subjects with the same mutation and also within the same family. CONCLUSION: This is the first and largest report of the clinical and molecular genetics of 5-α reductase deficiency from the Middle East. It shows weak genotype/phenotype correlation and significant phenotypic heterogeneity. IVS1-2A > G mutation is the most common mutation and is likely to be a founder mutation in this part of the world.

Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR): clinical heterogeneity and long-term efficacious management of eight patients from four unrelated Arab families with a loss of function VDR mutation.

BACKGROUND: Vitamin D regulates the concentrations of calcium and phosphate in blood and promotes the growth and remodeling of bones. The circulating active form of vitamin D, 1,25-dihydroxyvitamin D, binds to the vitamin D receptor (VDR), which heterodimerizes with the retinoid X receptor to regulate the expression of target genes. Inactivating mutations in the VDR gene cause hereditary vitamin D-resistant rickets (HVDRR), a rare disorder characterized by an early onset of rickets, growth retardation, skeletal deformities, hypocalcemia, hypophosphatemia and secondary hyperparathyroidism, and in some cases alopecia. METHODS: We describe eight new HVDRR patients from four unrelated consanguineous families. The VDR gene was sequenced to identify mutations. The management of patients over a period of up to 11 years following the initial diagnosis is assessed. RESULTS: Although all patients exhibit main features of HVDRR and carry the same c.885C>A (p.Y295*) loss of function mutation in the VDR gene, there was heterogeneity of the manifestations of HVDRR-associated phenotypes and developmental milestones. These eight patients were successfully treated over a period of 11 years. All clinical symptoms were improved except alopecia. CONCLUSIONS: The study concludes that VDR sequencing and laboratory tests are essential to confirm HVDRR and to assess the effectiveness of the treatment.

A high rate of novel CYP11B1 mutations in Saudi Arabia.

Despite ethnic variation, 11 ß-hydroxylase deficiency (11ß-OHD) has generally been considered the second most common subtype of congenital adrenal hyperplasia (CAH). We report a high rate of novel mutations in this gene (CYP11B1) in patients from Saudi Arabia. We studied 16 patients with 11ß-OHD from 8 unrelated families. DNA was isolated from peripheral blood. The 9 exons and exon-intron boundaries of CYP11B1 were PCR-amplified and directly sequenced. The novel mutations were functionally characterized using subcloning, in vitro mutagenesis, cell transfection and 11-deoxycortisol: cortisol conversion assays. Six mutations were found in these 8 unrelated families. Three of these mutations are completely novel and two have just been recently described as novel mutations from the same population. These include a single nucleotide insertion mutation in codon 18 (c.53_54insT) leading to frameshift and truncation in 4 siblings, a novel mutation (c.1343G>C, p.R448P) in 3 unrelated families, a novel mutation (c.1394A>T, p.H465L) in 2 siblings, a novel mutation (c.617G>T, p.G206V) in 1 patient, and a recently described non-sense novel mutation (c.780G>A, p.W260X) in another patient. Out of the 6 mutations described in this report, only one mutation (p.Q356X) was reported previously. In vitro functional testing of the 3 missense and nonsense novel mutations revealed complete loss of the 11 hydroxylase activity. We conclude that 11 ß-OHD in Saudi Arabia has a unique genotype with a high rate of novel mutations. The novel p. R448P mutation is the most common mutation in this highly inbred population.

Two novel LHX3 mutations in patients with combined pituitary hormone deficiency including cervical rigidity and sensorineural hearing loss.

BACKGROUND: Congenital combined pituitary hormone deficiency (CPHD) is a rare heterogeneous group of conditions. CPHD-type 3 (CPHD3; MIM# 221750) is caused by recessive mutations in LHX3, a LIM-homeodomain transcription factor gene. The isoforms of LHX3 are critical for pituitary gland formation and specification of the anterior pituitary hormone-secreting cell types. They also play distinct roles in the development of neuroendocrine and auditory systems. CASE PRESENTATION: Here, we summarize the clinical, endocrinological, radiological and molecular features of three patients from two unrelated families. Clinical evaluation revealed severe CPHD coupled with cervical vertebral malformations (rigid neck, scoliosis), mild developmental delay and moderate sensorineural hearing loss (SNHL). The patients were diagnosed with CPHD3 based on the array of hormone deficiencies and other associated syndromic symptoms, suggestive of targeted LHX3 gene sequencing. A novel missense mutation c.437G > T (p. Cys146Phe) and a novel nonsense mutation c.466C > T (p. Arg156Ter), both in homozygous forms, were found. The altered Cys146 resides in the LIM2 domain of the encoded protein and is a phylogenetically conserved residue, which mediates LHX3 transcription factor binding with a zinc cation. The p. Arg156Ter is predicted to result in a severely truncated protein, lacking the DNA binding homeodomain. CONCLUSIONS: Considering genotype/phenotype correlation, we suggest that the presence of SNHL and limited neck rotation should be considered in the differential diagnosis of CPHD3 to facilitate molecular diagnosis. This report describes the first LHX3 mutations from Saudi patients and highlights the importance of combining molecular diagnosis with the clinical findings. In addition, it also expands the knowledge of LHX3-related CPHD3 phenotype and the allelic spectrum for this gene.

Knowledge, awareness, attitudes and sources of vitamin D deficiency and sufficiency in Saudi children.

OBJECTIVES: To examine the awareness, knowledge, and attitudes regarding vitamin D and its sources among Saudi Arabian children.  METHODS: One hundred patients (vitamin D-deficient children) and 100 healthy children participated in the study. Participants were interviewed separately on topics including their awareness, knowledge, and attitudes regarding vitamin D using multiple-choice, and short-answer questions. This prospective, cross-sectional study was performed on children and adolescents between January 2011 and December 2011 at the Security Forces Hospital, Riyadh, Saudi Arabia.  RESULTS: Only 28% were aware of the sources of vitamin D, while 64% of healthy subjects were aware. Similarly, only 50% of patients and their parents knew of the health benefits of vitamin D, while 70% of healthy subjects had knowledge. Hence, our findings agree with previous findings that low levels of awareness and knowledge regarding vitamin D and its sources persist.   CONCLUSION: Most vitamin D deficient cases were unaware of vitamin D sources. However, half of the patient/parents were aware of benefits of vitamin D. Hence, we recommend that an improved campaign for awareness, knowledge, and attitudes regarding vitamin D and its sources are needed.

Diagnosis and management of growth disorders in Gulf Cooperation Council (GCC) countries: Current procedures and key recommendations for best practice.

Diagnosis and management of growth disorders comprises an important area of pediatric practice. Current procedures in the different stages of the identification, referral, investigation, and treatment of growth disorders in the Gulf Cooperation Council (GCC) countries have been summarized. Evidence-based procedures, relating specifically to height screening for identification of short stature, auxological criteria for patient referral from primary to secondary pediatric care, and general and endocrine investigations and diagnosis have been discussed and outlined. The management issues related to key disorders that are licensed for growth hormone (hGH) therapy, namely GH deficiency, Turner syndrome, short stature related to birth size small for gestational age (SGA), and idiopathic short stature are discussed with recommendations described for best practice. Finally, two key components of short stature management, namely transitional care for the transfer of patients from pediatric to adult endocrinology services and adherence to recommended therapy with hGH, have been addressed with current practice outlines and recommendations presented.

Decline in menarcheal age among Saudi girls.

OBJECTIVES: To estimate age at menarche and to assess trends in menarcheal age among Saudi women. METHODS: A prospective longitudinal study was conducted among healthy prepubertal female school children and adolescents from September 2006 to July 2012 in Riyadh, Kingdom of Saudi Arabia. Study participants were invited from diverse socioeconomic backgrounds. Tanner stage, height, weight, body mass index, and socioeconomic parameters including parent's level of education were collected. Age at menarche was compared with maternal age at menarche. RESULTS: The study included 265 girls and mothers. Mean±standard deviation (SD) age at menarche for girls was 13.08 ± 1.1 years, and their distribution category across the ≤10 years was 4 (1.5%), 11-14 years was 239 (90.2%), and ≥15 years was 22 (8.3%) girls. Anthropometric measurements, mother's level of education, and family income were not statistically significant determining factors associated with age at menarche. Mean ± SD age at menarche for mothers was 13.67 ± 1.4 years, and their distribution category across the ≤10 years was 7 (2.6%), 11-14 years was 172 (64.9%), and ≥15 years was 86 (32.5%). Girls attained menarche at younger age compared with their mothers (p less than 0.0001). A downward secular trend in age of menarche was observed (Cuzick test for trend = 0.049). CONCLUSION: Saudi girls attain menarcheal age earlier than their mothers, reflecting a downward secular trend in menarcheal age.

Effect of mobile phone short text messages on glycemic control in type 2 diabetes.

BACKGROUND: Mobile phone text messaging has rapidly become a socially popular form of communication. Several studies showed that mobile phone might offer a useful means of providing information between clinic visits and might increase adherence to diabetes therapy regimens. OBJECTIVES: We conducted a study to evaluate the effect of mobile phone short message service (SMS) on glycemic control in Saudi patients with type 2 diabetes. PATIENTS AND METHODS: One hundred patients (mean age, 41 ± 9.5 years) were selected at the Security Forces Hospital, Riyadh, Saudi Arabia, and provided with daily educational, reminding SMS messages for four months. Glycosylated hemoglobin (HbA1c) level, frequency of hypoglycemic and hyperglycemic attacks, and compliance with blood glucose monitoring were recorded before and after the trial. RESULTS: In addition to significant improvement in patients' knowledge, mean fasting blood glucose level improved from 8.60 ± 3.16 to 7.77 ± 3.11 mmol/L and mean HbA1c decreased from 9.9% ± 1.8% to 9.5% ± 1.7%. CONCLUSIONS: Mobile phone text messaging increased adherence to diabetes therapy and improved the clinical outcome in Saudi patients with type 2 diabetes.

Hypochondroplasia, Acanthosis Nigricans, and Insulin Resistance in a Child with FGFR3 Mutation: Is It Just an Association?

FGFR3 mutations cause wide spectrum of disorders ranging from skeletal dysplasias (hypochondroplasia, achondroplasia, and thanatophoric dysplasia), benign skin tumors (epidermal nevi, seborrhaeic keratosis, and acanthosis nigricans), and epithelial malignancies (multiple myeloma and prostate and bladder carcinoma). Hypochondroplasia is the most common type of short-limb dwarfism in children resulting from fibroblast growth factor receptor 3 (FGFR3) mutation. Acanthosis nigricans might be seen in severe skeletal dysplasia, including thanatophoric dysplasia and SADDAN syndrome, without a biochemical evidence of hyperinsulinemia. Insulin insensitivity and acanthosis nigricans are uncommonly seen in hypochondroplasia patients with FGFR3 mutations which may represent a new association. We aim to describe the association of hypochondroplasia, acanthosis nigricans, and insulin resistance in a child harboring FGFR3 mutation. To our knowledge, this is the first case report associating the p.N540 with acanthosis nigricans and the second to describe hyperinsulinemia in hypochondroplasia. This finding demonstrates the possible coexistence of insulin insensitivity and acanthosis nigricans in hypochondroplasia patients.

Divergent gender identity in three siblings with 46XX karyotype and severely virilizing congenital adrenal hyperplasia caused by a novel CYP11B1 mutation.

OBJECTIVE: To describe conflicting gender identities in three karyotypically female siblings with congenital adrenal hyperplasia (CAH) caused by a novel mutation in the CYP11B1 gene, who were assigned as males at birth and followed up to adulthood. METHODS: We present 3 siblings (16, 14 and 10 years old) who were born with severe genital virilization and raised as males. Clinical examination showed Prader IV to V external genitalia with a stretched penile length of 7 to 11 cm. Adrenocorticotrophic hormone (ACTH) stimulation test showed a stimulated 11 deoxycortisol (11DOC) level of 12,300-18,700 µg/L (normal 0-5 µg/L). Their karyotypes were 46 XX, and they had normal-sized uterus and ovaries on pelvic ultrasound. DNA was isolated from peripheral leukocytes, and polymerase chain reaction (PCR) and direct sequencing revealed a novel CYP11B1 mutation. This mutation leads to a c.53_54 T insertion (c.53_54insT) with frameshift and truncation at c.115 (codon 39) of CYP11B1. RESULTS: Psychological evaluation of the oldest sibling suggested a female gender identity, and she declared herself as female, and female sex was re-assigned after 1 year of psychosocial adjustment. Psychological assessment for the 2 younger siblings and a fourth 46XY sibling with the same condition revealed male gender identities, and they continued their lives as males without significant difficulties. CONCLUSION: Divergent gender identity was observed in three severely masculinized 46XX siblings with CAH who carried the same CYP11B1 mutation and had comparable postnatal and probably prenatal androgen exposure and environmental circumstances. These cases suggest that the basis of gender identity is more complex than chromosomal, biochemical, and genetic constitution.

Effect of mobile phone short text messages on glycaemic control in children with type 1 diabetes.

We conducted a feasibility study of a mobile phone messaging service for children and adolescents with type 1 diabetes. Two hundred children with type 1 diabetes took part in a six-month trial. The children were provided - through their parents - with daily information messages, with weekly interactive messages, and on request, with multimedia video messages about procedures related to diabetes care. During the study, approximately 30,000 information messages and 2800 interactive messages were sent. One month before the trial, the mean fasting blood glucose level of the children was 150 mg/dl. After the trial, the mean fasting blood glucose level was 133 mg/dl (P < 0.001). There were also significant reductions in post prandial blood glucose level, HbA1c, frequency of simple hypoglycaemic attacks and frequency of blood glucose monitoring. A before and after questionnaire showed that the parents' knowledge of diabetes had improved significantly during the trial. Mobile phone text messaging offers a useful means of contact between clinic visits. The results of the trial suggest that it increases adherence to diabetes therapy and improves clinical outcomes in children and adolescents with type 1 diabetes.