The Natural History of Symptomatic Fractures in Children and Adolescents with Osteogenesis Imperfecta Type 1: A Cohort Study from Western Australia.

The fracture experience of children and adolescents with osteogenesis imperfecta (OI) type 1 is not well described in the literature. We present data on symptomatic long bones and axial skeleton fractures of all patients aged 0 to 18 years with OI type 1 seen at a specialized bone clinic in Western Australia in the period 2008 to 2020 using a retrospective chart review method. The cohort consisted of 44 patients (21 males, 23 females). Median (interquartile range [IQR]) age was 11.3 (6.2 to 17) years, giving a total of 520 patient-years in the study during which 197 fractures were experienced. The mean fracture rate was 379 fractures per 1000 patient-years (95% confidence interval [CI]: 310 to 440); however, the experience for fractures varied from ≤1 fracture in 23% (n = 10) to two to 20 in 77% (n = 34) of the cohort. Twenty-one patients (48.5%) received bisphosphonates during the study period. In logistic regression, age, but not sex or family history of OI, was a significant predictor of fracture risk. The highest total fracture rate was observed in the age group 0 to <3 years at 469 fractures/1000 patient-years, which declined to 140 fractures/1000 patient-years in the age group 15 to 18 years. The lower limbs were the site of 49.7% of all fractures. The highest rate for lower limb fracture was in the age group 0 to <3 years at 331 fractures/1000 patient-years, decreasing to 0 fractures/1000 patient-years in the age group 15 to 18 years. Upper limb fracture rates increased from 100 fractures/1000 patient-years in the 0 to <3 years age group to 307 fractures/1000 patient-years in the 9 to <12 years age group and then declining to 70 fractures/1000 years in the 15 to 18 years age group. In pediatric patients with OI type 1, fracture risk is highest in early life, especially in the lower limbs. Multidisciplinary care of children with OI should have a particular focus on strategies to prevent these fractures. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Role of HLA-DQ typing and anti-tissue transglutaminase antibody titers in diagnosing celiac disease without duodenal biopsy in type 1 diabetes: A study of the population-based pediatric type 1 diabetes cohort of Western Australia.

AIM: The primary aim of the present study was to determine if it is cost effective to use human leukocyte antigen (HLA) typing as a first-line screening test for celiac disease (CD) in children with type 1 diabetes (T1D), as recommended by the European Society of Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN). The second aim was to investigate whether anti-tissue transglutaminase IgA (anti-tTGA) antibodies can be used to diagnose CD without the need for a confirmatory duodenal biopsy in T1D. METHODS: Data for all T1D patients aged <18 years, who attended the diabetes clinics in Western Australia up to June 2017, were extracted from the Western Australian Children's Diabetes Database (WACDD) and analyzed for their demographic data and CD permissive HLA alleles (DQ2, DQ8, and DQ7). For T1D patients already diagnosed with CD, the mode of diagnosis of CD, anti-tTGA titers, and CD permissive HLA alleles were analyzed. RESULTS: Of the 936 eligible T1D patients identified, HLA-DQ typing was available for 551 (59%). Of these 551 patients, 504 (91.2%) were positive for celiac permissive HLA alleles. Eight percent (n = 75) of the T1D patients had a co-diagnosis of CD. High anti-tTGA titers were observed in those who were diagnosed with a positive duodenal biopsy. CONCLUSION: HLA-DQ typing is not cost effective as a first-line screening test for CD in T1D patients because of over-representation of CD permissive HLA alleles in this group. Anti-tTGA titers may be useful in diagnosing CD in T1D without duodenal biopsy, as high levels were found to be strongly predictive of CD.

A novel, homozygous mutation in desert hedgehog (DHH) in a 46, XY patient with dysgenetic testes presenting with primary amenorrhoea: a case report.

BACKGROUND: Desert hedgehog (DHH) mutations have been described in only a limited number of individuals with 46, XY disorders of sex development (DSD) presenting as either partial or complete gonadal dysgenesis. Gonadal tumours and peripheral neuropathy have been associated with DHH mutations. Herein we report a novel, homozygous mutation of DHH identified through a targeted, massively parallel sequencing (MPS) DSD panel, in a patient presenting with partial gonadal dysgenesis. This novel mutation is two amino acids away from a previously described mutation in a patient who presented with complete gonadal dysgenesis. Adding to the complexity of work-up, our patient also expressed gender identity concern. CASE PRESENTATION: A 14-year-old, phenotypic female presented with primary amenorrhoea and absent secondary sex characteristics. Investigations revealed elevated gonadotrophins with low oestradiol, testosterone of 0.6 nmol/L and a 46, XY karyotype. Müllerian structures were not seen on pelvic ultrasound or laparoscopically and gonadal biopsies demonstrated dysgenetic testes without neoplasia (partial gonadal dysgenesis). The patient expressed gender identity confusion upon initial notification of investigation findings. Formal psychiatric evaluation excluded gender dysphoria. Genetic analysis was performed using a targeted, MPS DSD panel of 64 diagnostic and 927 research candidate genes. This identified a novel, homozygous mutation in exon 2 of DHH (DHH:NM_021044:exon2:c.G491C:p.R164P). With this finding our patient was screened for the possibility of peripheral neuropathy which was not evident clinically nor on investigation. She was commenced on oestrogen for pubertal induction. CONCLUSION: The evaluation of patients with DSD is associated with considerable psychological distress. Targeted MPS enables an affordable and efficient method for diagnosis of 46, XY DSD cases. Identifying a genetic diagnosis may inform clinical management and in this case directed screening for peripheral neuropathy. In addition to the structural location of the mutation other interacting factors may influence phenotypic expression in homozygous DHH mutations.

Comparable glycemic outcomes for pediatric type 1 diabetes patients in metropolitan and non-metropolitan regions of Western Australia: A population-based study.

BACKGROUND: Pediatric patients diagnosed with type 1 diabetes (T1D) in Western Australia (WA) are managed by a single, specialist multidisciplinary diabetes service based at a central tertiary hospital in the capital city, Perth, which provides outreach care in regional centers. OBJECTIVE: To investigate the hypothesis that outcomes for a contemporary, population-based pediatric T1D cohort, managed by a single tertiary service are similar for metropolitan and non-metropolitan patients using this model of care. To confirm that the cohort is indeed population based, a secondary aim of the study was to determine the case ascertainment of the Western Australian Children's Diabetes Database (WACDD). METHODS: Data for all T1D patients aged <18 years, who attended the diabetes clinics (metropolitan and non-metropolitan), at least once in 2014, were extracted from the WACDD and outcomes including HbA1c and severe hypoglycemia (SH) rates analyzed. RESULTS: In 2014, a total of 1017 patients (492 females, 525 males) attended the diabetes clinics (54% metropolitan and 46% non-metropolitan). After adjusting for age, sex, diabetes duration, and insulin regimen, region of clinic was not a significant predictor of mean HbA1c or SH rate. The case ascertainment of the WACDD was estimated to be 99.9% complete for children diagnosed with T1D aged <15 years between 2002 and 2012. CONCLUSIONS: This study reports similar glycemic outcomes for patients attending diabetes clinics in metropolitan and non-metropolitan areas of WA, suggesting that a model of care provided as outreach from a specialized diabetes service is effective in achieving equitable glycemic outcomes.