Family mapping of previously identified HPP patients (FAME study)

• Research type

  Research Study

• Full title

  Family mapping of previously identified HPP patients using predictive genotyping and detailed phenotyping approach

• IRAS ID

  301025

• Contact name

  Aimee Card

• Contact email

  aimee.card@nhs.net

• Sponsor organisation

  Sheffield Teaching Hospitals NHS FT

• Duration of Study in the UK

  1 years, 10 months, 1 days

• Research summary

  Hypophosphatasia (HPP) is an inherited condition, caused by a fault in the ALPL gene. HPP causes a defect in bone mineralization, leading to weak bones. Early childhood forms are severe and easily recognizable, and there is now a drug treatment which is very effective in children. Adult forms can vary in severity. HPP is often missed by doctors or confused with osteoporosis. It is however important to make the distinction because the usual osteoporosis treatments may be harmful in HPP, and increase the risk of broken bones. One of the reasons it is missed is a lack of research describing the typical features of HPP, so doctors don’t recognise the signs, and don’t know when or how to test for it.
  Different gene faults have different manifestations, and we do not know what to expect for each gene fault. Sometimes, people with the same gene fault have different manifestations.
  We will study families to find out who has the gene fault and what are their range of symptoms. We will check if these symptoms are associated with specific gene faults. This will help us to understand how the gene fault affects people in different ways and how the defective gene is transmitted within families. These results will also help us to estimate which manifestations to expect in people who have gene faults.

  Lay Summary of Results:

  Hypophosphatasia (HPP) is a rare genetic condition caused by changes in the ALPL gene, leading to reduced activity of an enzyme called alkaline phosphatase (ALP), which is important for bone mineralization. Adults with HPP often show varied symptoms, and there is no single typical presentation. In our study, we invited individuals with a confirmed genetic change in ALPL and their relatives. We compared the relatives with and without the gene change. We used blood and physical tests, and questionnaires to evaluate their symptoms, physical function, and quality of life. Blood tests measured markers related to bone and mineral health, while surveys assessed pain, arthritis, and daily living impact. We found that people with the ALPL change had lower ALP levels, higher phosphate levels, and other differences in blood markers compared to relatives without the gene change. However, musculoskeletal symptoms, such as fractures or bone pain, were similar in both groups. While those with the gene variant reported slightly more pain, it was not a statistically significant difference. Physical performance and quality of life also showed no major differences. In conclusion, relatives with the ALPL change showed more biochemical abnormalities, but their symptoms and quality of life were not significantly worse than those without the genetic change.
  Has the registry been updated to include summary results?: No
  If yes - please enter the URL to summary results:
  If no – why not?: Not registered
  Did you follow your dissemination plan submitted in the IRAS application form (Q A51)?: Yes
  If yes, describe or provide URLs to disseminated materials: No URLs
  If pending, date when dissemination is expected:
  If no, explain why you didn't follow it:
  Have participants been informed of the results of the study?: No
  If yes, describe and/or provide URLs to materials shared and how they were shared:
  If pending, date when feedback is expected:
  If no, explain why they haven't: Not mentioned on the PIS
  Have you enabled sharing of study data with others?: Yes
  If yes, describe or provide URLs to how it has been shared: We have published the results on peer reviewed journals and presented in conferences. No further data sharing.
  If no, explain why sharing hasn't been enabled:
  Have you enabled sharing of tissue samples and associated data with others?: No
  If yes, describe or provide a URL:
  If no, explain why: No tissue samples associated with the study
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• REC name

  South Central - Oxford A Research Ethics Committee

• REC reference

  21/SC/0376

• Date of REC Opinion

  17 Nov 2021

• REC opinion

  Favourable Opinion