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Hypophosphatasia United States Molecular Research Center

Hypophosphatasia is a disease that affects the development of bones and teeth.  Sometimes people appear to have hypophosphatasia, but their molecular testing does not reflect this diagnosis.  The purpose of this research study is to take a deeper look at the genes of people who clinically appear to have the diagnosis of hypophosphatasia but do not have a pathogenic variant to prove their diagnosis.

Information for Patients

 

Thank you for your interest in the Hypophosphatasia United States Molecular Research Center.  Your participation makes a difference and could lead to new answers for people with Hypophosphatasia. 

Any individual over 1 month of age with a clinical diagnosis of hypophosphatasia and a lack of detection of a variant on molecular analysis of the ALPL gene.  

There is no cost to participate. 

  • You will sign a medical release form
  • Medical information will be collected by the study team from your nominating provider to include your past medical history, lab results, radiology results and genetic test results
  • A study team member will contact you to review and have you sign the study consent form. If your child is participating, they may also need to agree to participate
  • A blood sample will be taken and sent to Children’s Mercy Hospital
  • Your provider will be notified of your results and will update you with the results

For more information, please email the study team at hpp@cmh.edu.

Information for Providers

 

Thank you for your interest in the Hypophosphatasia United States Molecular Research Center. This study is being done to determine if cryptic alterations exist within or near to the ALPL gene in patients with a clinical diagnosis of hypophosphatasia, but without identifiable alteration on commercial testing. We also aim to characterize functional effects of certain variants of uncertain significance in patients with clinical diagnosis of hypophosphatasia.

Inclusion Criteria – Aim 1

  1. Diagnosis of Hypophosphatasia based on clinical features that include   
    • History consistent with diagnosis of hypophosphatasia AND
    • Physical examination findings consistent with a diagnosis of hypophosphatasia AND
    • Presence of low serum alkaline phosphatase level for age and sex AND
    • Elevation of at least one natural substrate of alkaline phosphatase
  2. Lack of detection of a variant on molecular analysis of the ALPL gene.

Inclusion criteria – Aim 2

  1. Missense variant in ALPL which is interpreted as a variant of uncertain significance by the American College of Medical Genetics Guidelines for Variant Interpretation
  2. Variant has been interpreted as pathogenic, likely pathogenic, likely benign, or benign using ex-US interpretation guidelines

Exclusion criteria – Aim 1

  1. History and physical examination incompatible with a diagnosis of hypophosphatasia OR
  2. Absence of hypophosphatasemia as measured by age and sex-matched control OR
  3. Absence of at least one elevated natural substrate of alkaline phosphatase OR
  4. Alternate diagnosis which could overlap with signs and symptoms of hypophosphatasia

Exclusion criteria – Aim 2

  1. Inability to express variant in plasmid for residual enzyme and co-transfection analyses

Click here to fill out a form to nominate your patient.

Please upload the participant's signed Medical Release Form with your nomination. It has been pre-filled out to account for this study's specific needs. 

For more information, please email the study team at hpp@cmh.edu.

Children's Mercy Kansas City   /    Children’s Mercy Research Institute   /    Research Studies and Clinical Trials   /   Hypophosphatasia United States Molecular Research Center