A Retrospective Study of the Natural History of Patients With Severe Perinatal and Infantile Hypophosphatasia (HPP)

Completed

Brief Summary: This study aims to characterize the natural history of patients with severe perinatal or infantile onset HPP.

Detailed Description: Hypophosphatasia (HPP) is a life-threatening, genetic, and ultra-rare metabolic disease characterized by defective bone mineralization and impaired phosphate and calcium regulation that can lead to progressive damage to multiple vital organs, including destruction and deformity of bones, profound muscle weakness, seizures, impaired renal function, and respiratory failure. There are no approved disease-modifying treatments for patients with this disease. There is also limited data available on the natural course of this disease over time, particularly in patients with the juvenile-onset form.

Recruitment & Eligibility

Inclusion Criteria

Parent(s) or legal guardian(s) must provide written informed consent prior to data abstraction, unless all of the following apply:
The patient is deceased; AND
The responsible IRB/IEC/REB does not require informed consent per a review of their documented local policies for collecting retrospective data on patients who are deceased; AND
Written confirmation is received from the responsible IRB/IEC/REB confirming that the abstracted data can be analyzed and used to support regulatory filings by the Sponsor
Patient must have a documented diagnosis of HPP as indicated by 1 or more of the following:
Documented ALPL gene mutation(s)
Serum alkaline phosphatase (ALP) below the age-adjusted normal range and either plasma pyridoxal 5'-phosphate (PLP) or urinary phosphoethanolamine (PEA) above the upper limit of normal
Serum ALP below the age-adjusted normal range and HPP-related radiographic abnormalities on X-ray
Patient must have onset of signs of HPP prior to 6 months of age and have documentation of 1 or more of the following characteristics of perinatal and infantile HPP:
Respiratory compromise (up to and including respiratory failure) requiring institution of respiratory support measure(s), requiring medication(s) for management of symptom(s), and/or associated with other respiratory complications (e.g., pneumonia(s), respiratory tract infection(s))
Pyridoxine (vitamin B6)-responsive seizures
Rachitic chest deformity

Exclusion Criteria

Patients will be excluded from study participation if they have 1 or more of the following exclusion criteria:

Patient received treatment with asfotase alfa at any time prior to data abstraction
Patient has clinically significant other disease

Both living and deceased patients will be considered for study participation

Primary Outcome Measures

Name	Time	Method
Survival	Retrospective data collected on or before the data of abstraction.	Overall survival is defined as the time from birth to time of death.

Secondary Outcome Measures

Name	Time	Method
Invasive Ventilator-free Survival Time	Retrospective data collected on or before the date of abstraction.	Invasive ventilator-free survival is defined as the time during which the patient is alive and not invasively ventilated. For the purpose of this study, invasive ventilation is defined as mechanical ventilation via intubation of trachaeostomy.

Locations (12): Cedars-Sinai Medical Center
🇺🇸
Los Angeles, California, United States
Indiana University school of medicine
🇺🇸
Indianapolis, Indiana, United States
Shriners Hospital for Children
🇺🇸
Saint Louis, Missouri, United States
Oregon Health & Science University
🇺🇸
Portland, Oregon, United States
University of Manitoba Health Sciences Centre
🇨🇦
Winnipeg, Canada
Birmingham Childrens Hospital
🇬🇧
Birmingham, United Kingdom
Universitätsklinikum Würzburg Kinderklinik, Pädiatrische Infektiologie und Immunologie
🇩🇪
Würzburg, Germany
Universitatsmedizin Mainz, Villa
🇩🇪
Mainz, Germany
Royal Children's Hospital
🇦🇺
Parkville, Australia
Hospital Infantil Universitario Nino Jesus Universidad autonoma de Madrid
🇪🇸
Madrid, Spain
National Taiwan University Hospital
🇨🇳
Taipei, Taiwan
Cook Children's Health Care System
🇺🇸
Fort Worth, Texas, United States