A Retrospective Study of the Natural History of Patients With Severe Perinatal and Infantile Hypophosphatasia (HPP)
A Retrospective Study of the Natural History of Patients With Severe Perinatal and Infantile Hypophosphatasia (HPP)
This study aims to characterize the natural history of patients with severe perinatal or
 infantile onset HPP.
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.
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