Enzyme replacement therapy for hypophosphatasia-The current paradigm.

Hypophosphatasia (HPP) is a rare, inherited, and systemic disorder characterized by impaired skeletal mineralization and low tissue nonspecific serum alkaline phosphatase (TNSALP) activity. It is caused by either autosomal recessive or dominant-negative mutations in the gene that encodes TNSALP. The phenotype of HPP is very broad including abnormal bone mineralization, disturbances of calcium and phosphate metabolism, pain, recurrent fracture, short stature, respiratory impairment, developmental delay, tooth loss, seizures, and premature death.

Genotyping in patients with congenital adrenal hyperplasia by sequencing of newborn bloodspot samples.

Objectives: Genotype-phenotype correlation in congenital adrenal hyperplasia (CAH) caused by 21-hydroxylase deficiency ranges from 45 to 97 %. We performed massively parallel sequencing of on stored newborn bloodspot samples to catalogue the genotypes present in our patients with CAH and enable genotype-phenotype comparison.

Methods: Participants ≤15 years old with clinically diagnosed CAH were recruited from The Sydney Children's Hospitals Network.

X-linked hypophosphatemia caused by a deep intronic variant in PHEX identified by PCR-based RNA analysis of urine-derived cells.

X-linked hypophosphatemia (XLH) is caused by dominant inactivating mutations in the phosphate regulating endopeptidase homology, X-linked (PHEX), resulting in elevated fibroblast growth factor 23 (FGF23), hypophosphatemia, rickets and osteomalacia. PHEX variants are identified in approximately 85 % of individuals with XLH, which leaves a substantial proportion of patients with negative DNA-based genetic testing. Here we describe a 16-year-old male who had typical features of XLH on clinical and radiological examination.

Craniofacial and dental phenotype of two girls with osteogenesis imperfecta due to mutations in CRTAP.

Mutations in CRTAP lead to an extremely rare form of recessive osteogenesis imperfecta (OI). CRTAP deficient mice have a brachycephalic skull, fusion of facial bones, midface retrusion and class III dental malocclusion, but in humans, the craniofacial and dental phenotype has not been reported in detail. Here, we describe craniofacial and dental findings in two 11-year-old girls with biallelic CRTAP mutations.

Dominant osteogenesis imperfecta with low bone turnover caused by a heterozygous SP7 variant.

Mutations in SP7 (encoding osterix) have been identified as a rare cause of recessive osteogenesis imperfecta ('OI type XII') and in one case of dominant juvenile Paget's disease. We present the first description of young adult siblings with OI due to a unique heterozygous mutation in SP7. The phenotype was characterized by fragility fractures (primarily of the long bone diaphyses), poor healing, scoliosis, and dental malocclusion.

Type 2 diabetes in children and adolescents across Australia and New Zealand: A 6-year audit from The Australasian Diabetes Data Network (ADDN).

Objectives: To assess the clinical and demographic characteristics of children and adolescents across Australia and New Zealand (NZ) with type 2 diabetes.

Methods: We performed a descriptive audit of data prospectively reported to the Australasian Diabetes Data Network (ADDN) registry. Data were collected from six tertiary pediatric diabetes centers across Australia (New South Wales, Queensland, South Australia, Western Australia, and Victoria) and NZ (Auckland).

Screening, assessment and management of type 2 diabetes mellitus in children and adolescents: Australasian Paediatric Endocrine Group guidelines.

Introduction: The incidence of type 2 diabetes mellitus has increased in children and adolescents due largely to the obesity epidemic, particularly in high risk ethnic groups. β-Cell function declines faster and diabetes complications develop earlier in paediatric type 2 diabetes compared with adult-onset type 2 diabetes. There are no consensus guidelines in Australasia for assessment and management of type 2 diabetes in paediatric populations and health professionals have had to refer to adult guidelines.