Mutations That Alter the Carboxy-Terminal-Propeptide Cleavage Site of the Chains of Type I Procollagen Are Associated With a Unique Osteogenesis Imperfecta Phenotype.

Osteogenesis imperfecta (OI) is a genetic bone disorder characterized by fractures, low bone mass, and skeletal fragility. It most commonly arises from dominantly inherited mutations in the genes COL1A1 and COL1A2 that encode the chains of type I collagen. A number of recent reports have suggested that mutations affecting the carboxyl-terminal propeptide cleavage site in the products of either COL1A1 or COL1A2 give rise to a form of OI characterized by unusually dense bones. We have assembled clinical, biochemical, and molecular data from 29 individuals from 8 families with 7 different mutations affecting the C-propeptide cleavage site. The phenotype was generally mild: The median height was ∼33th centile. Eighty percent of subjects had their first fracture by the age of 10 years, and one-third had a femoral or tibial fracture by the age of 25 years. Fractures continued into adulthood, though rates varied considerably. Healing was normal and rarely resulted in long bone deformity. One-third of subjects older than 15 years had scoliosis. The teeth and hearing were normal in most, and blue sclerae were not observed. Other features noted included fibro-osseous dysplasia of the mandible and Achilles tendon calcification. The mean spinal bone mineral density Z-score was +2.9 (SD 2.1) compared with -2.2 (0.7) in subjects with COL1A1 haploinsufficiency mutations. Bone mineral density distribution, assessed by quantitative backscattered electron imaging in bone showed higher levels of mineralization than found in any other disorder. Bone histology showed high trabecular volume and increased cortical thickness, with hyperosteoidosis and delayed mineralization. In vitro studies with cultured skin fibroblasts suggested that these mutations interfere with processing of the chain in which the sequence alteration occurs, but the C-propeptide is eventually cleaved (and detectable in blood), suggesting there are alternative sites of cleavage. The precise mechanism of the bony pathology is not yet clear. © 2018 American Society for Bone and Mineral Research.

Increasing rates of people identifying as transgender presenting to Endocrine Services in the Wellington region.

AIMS: Overseas clinics specialising in management of transgender people have noted a marked increase in the numbers of people requesting therapy in the last few years. No data has been presented for New Zealand. We therefore reviewed the number of transgender people seen in the Wellington Endocrine Service to assess if the pattern was similar and assess any potential problems for service delivery. METHODS: Using hospital records, we reviewed the new appointments of people who were referred for advice on gender reassignment and seen in the Wellington Endocrine Service from 1990 to 2016. RESULTS: In total, 438 people who identified as transgender attended the clinic at least once in this period. There has been a progressive increase in number of people identifying as transgender presenting to the clinic, particularly since 2010. In addition to increasing overall numbers, there has been in particular increase in referrals for people under age 30, as well as an increasing proportion of people requesting female-to-male (FtM) therapy so that it is now approaching the number of people requesting male-to-female therapy (MtF). CONCLUSION: The pattern observed is comparable to changes reported overseas. These changes have practical consequences for the delivery of both secondary and primary level healthcare, requiring an increased focus on clinical coordination between the relevant medical services and their links to the primary services sector.

Specialist services for management of individuals identifying as transgender in New Zealand.

AIMS: In light of the rising number of referrals to secondary level services of people who identify as transgender, and the Human Rights Commission concerns regarding the care of this group in New Zealand, we felt it was timely to determine the availability of services for people who identify as transgender and whether there are variations in management protocols. METHODS: We contacted 100 physicians involved in providing a secondary level service to care for people who identify as transgender, and asked them to complete a questionnaire about the services available in their region. This questionnaire consisted of two parts, a 'general questionnaire', which focussed on the consultants' understanding of services available locally, and a 'clinical questionnaire', which presented hypothetical clinical case histories and asked respondents to indicate how they would manage the case. RESULTS: Sixty-two of the physicians responded. Of these, 18 (45% of the 40 physicians that answered the question) believed they could access a psychological or psychiatric opinion in the public sector for a patient who identifies as transgender, whereas 28 (82% of the 34 that answered the question) knew of access in the private sector. There was a conflict of opinion on the availability of psychological and surgical services in several DHBs where there was more than one clinician responding. This may reflect the case experience of individual clinicians. There was restricted access to common surgical procedures in the public sector, and about half of respondents did not know if techniques were available locally. CONCLUSIONS: Our results support the development of specialist care services in tertiary centres in addition to the secondary services already available in New Zealand for people who identify as transgender. Development of multidisciplinary management and improved access to psychological support services for individual cases is required.