Study of People With Generalized Arterial Calcification of Infancy (GACI) or Autosomal Recessive Hypophosphatemic Rickets Type 2 (ARHR2)
| Status: | Recruiting |
|---|---|
| Conditions: | Gastrointestinal |
| Therapuetic Areas: | Gastroenterology |
| Healthy: | No |
| Age Range: | Any - 100 |
| Updated: | 1/27/2019 |
| Start Date: | April 17, 2018 |
| End Date: | December 31, 2019 |
| Contact: | Carlos R Ferreira, M.D. |
| Email: | ferreiracr@mail.nih.gov |
| Phone: | (240) 393-5441 |
Background:
Generalized Arterial Calcification of Infancy (GACI) is a very rare disorder. It can be fatal
before birth or by age 6 months. Anumber of people with GACI survive into adulthood. Those
adults suffer from side effects of the disease, including rickets. It is unknown how common
the disease Autosomal Recessive Hypophosphatemic Rickets Type 2 (ARHR2) is. It also has side
effects. GACI and ARHR2 are usually caused by the mutations in the same gene. There are no
approved treatments for the two diseases. Researchers want to study people with these
diseases and their family members. This may help understand these rare and unique diseases
better. The data could lead to new treatments for GACI and ARHR2.
Objectives:
To better understand the progression of GACI and ARHR2 and how genes might play a role in
them.
Eligibility:
People with GACI or ARHR2, both living and deceased, and their parents and siblings.
Design:
Participants will allow researchers to access their medical records. They will give this
consent by mail, email, or fax.
Data will be taken from the records. Participants names will not be used. Instead, they will
be identified by a code.
Participants may give a blood sample.
If a participant withdraws from the study, their data and samples will be destroyed. However,
the coded clinical data in the official medical record and data in databases will NOT be
destroyed.
Generalized Arterial Calcification of Infancy (GACI) is a very rare disorder. It can be fatal
before birth or by age 6 months. Anumber of people with GACI survive into adulthood. Those
adults suffer from side effects of the disease, including rickets. It is unknown how common
the disease Autosomal Recessive Hypophosphatemic Rickets Type 2 (ARHR2) is. It also has side
effects. GACI and ARHR2 are usually caused by the mutations in the same gene. There are no
approved treatments for the two diseases. Researchers want to study people with these
diseases and their family members. This may help understand these rare and unique diseases
better. The data could lead to new treatments for GACI and ARHR2.
Objectives:
To better understand the progression of GACI and ARHR2 and how genes might play a role in
them.
Eligibility:
People with GACI or ARHR2, both living and deceased, and their parents and siblings.
Design:
Participants will allow researchers to access their medical records. They will give this
consent by mail, email, or fax.
Data will be taken from the records. Participants names will not be used. Instead, they will
be identified by a code.
Participants may give a blood sample.
If a participant withdraws from the study, their data and samples will be destroyed. However,
the coded clinical data in the official medical record and data in databases will NOT be
destroyed.
This is a retrospective, natural history study of patients with Generalized Arterial
Calcification of Infancy (GACI) or Autosomal Recessive Hypophosphatemic Rickets Type 2
(ARHR2). GACI is an ultra-rare disorder with an estimated birth prevalence of around 1 in
400,000.1 GACI is characterized by extensive arterial calcifications, arterial stenosis,
myointimal proliferation and periarticular calcifications. Individuals with GACI also
experience calcification in other body areas, such as joints and parenchymal organs.
GACI is generally fatal before birth or within the first six months after birth. The cause of
death is frequently myocardial infarction or stroke, and hypertension and congestive heart
failure are common in fetuses and infants with GACI. The first six months of life are
considered a critical period for GACI patients, and approximately 85% of infants with GACI do
not survive beyond this period (Moran 1975). However, the mortality rate decreases
substantially among patients who do survive beyond the critical period. Reports exist of
patients with GACI who survived into adulthood, but the frequency of this occurrence is
unknown, and adult patients suffer from a number of sequelae such as cognitive impairment
related to stroke. ARHR2 is characterized by short stature, dental caries, and bone
deformities, and biochemically by hypophosphatemia, hyperphosphaturia and elevated plasma
alkaline phosphatase. The disease frequency is unknown.
GACI and ARHR2 are most commonly due to mutations of ENPP1 (ectonucleotide
pyrophosphatase/phosphodiesterase 1), or less often from mutations in ABCC6 (adenosine
triphosphate binding cassette transporter protein subfamily C member 6). No founder mutations
are known, and thus no ethnic predilection is known. Both the GACI and ARHR2 phenotypes are
potentially fatal or associated with severe morbidity, with no FDA-approved drugs or proven
treatments. Animal data suggest that enzyme replacement therapy with ENPP1-Fc may be
effective in preventing morbidity or mortality of GACI and ARHR2.
PXE (pseudoxanthoma elasticum) is an autosomal recessive disorder due to mutations in ABCC6
or, less often, ENPP1. PXE is characterized by ectopic calcification of the skin, eyes,
cardiovascular system and gastrointestinal system. This study will not focus on PXE but will
collect data on PXE patients, particularly when their presentation suggests elements of the
GACI or ARHR2 phenotypes.
The main objective of this study is to collect historical control data for future comparison
to data from patients treated with ENPP1-Fc so we can develop ENPP1-Fc as a treatment for
GACI or ARHR2. In addition, this study will allow for a better understanding of the disease
course to design future treatment trials. The study will utilize data obtained predominantly
from chart review. The goal is to enroll 100 participants, which include both living and
deceased individuals with GACI or ARHR2, and/or their parents and siblings. Our study will be
jointly and collaboratively conducted by the NIH and Inozyme.
Calcification of Infancy (GACI) or Autosomal Recessive Hypophosphatemic Rickets Type 2
(ARHR2). GACI is an ultra-rare disorder with an estimated birth prevalence of around 1 in
400,000.1 GACI is characterized by extensive arterial calcifications, arterial stenosis,
myointimal proliferation and periarticular calcifications. Individuals with GACI also
experience calcification in other body areas, such as joints and parenchymal organs.
GACI is generally fatal before birth or within the first six months after birth. The cause of
death is frequently myocardial infarction or stroke, and hypertension and congestive heart
failure are common in fetuses and infants with GACI. The first six months of life are
considered a critical period for GACI patients, and approximately 85% of infants with GACI do
not survive beyond this period (Moran 1975). However, the mortality rate decreases
substantially among patients who do survive beyond the critical period. Reports exist of
patients with GACI who survived into adulthood, but the frequency of this occurrence is
unknown, and adult patients suffer from a number of sequelae such as cognitive impairment
related to stroke. ARHR2 is characterized by short stature, dental caries, and bone
deformities, and biochemically by hypophosphatemia, hyperphosphaturia and elevated plasma
alkaline phosphatase. The disease frequency is unknown.
GACI and ARHR2 are most commonly due to mutations of ENPP1 (ectonucleotide
pyrophosphatase/phosphodiesterase 1), or less often from mutations in ABCC6 (adenosine
triphosphate binding cassette transporter protein subfamily C member 6). No founder mutations
are known, and thus no ethnic predilection is known. Both the GACI and ARHR2 phenotypes are
potentially fatal or associated with severe morbidity, with no FDA-approved drugs or proven
treatments. Animal data suggest that enzyme replacement therapy with ENPP1-Fc may be
effective in preventing morbidity or mortality of GACI and ARHR2.
PXE (pseudoxanthoma elasticum) is an autosomal recessive disorder due to mutations in ABCC6
or, less often, ENPP1. PXE is characterized by ectopic calcification of the skin, eyes,
cardiovascular system and gastrointestinal system. This study will not focus on PXE but will
collect data on PXE patients, particularly when their presentation suggests elements of the
GACI or ARHR2 phenotypes.
The main objective of this study is to collect historical control data for future comparison
to data from patients treated with ENPP1-Fc so we can develop ENPP1-Fc as a treatment for
GACI or ARHR2. In addition, this study will allow for a better understanding of the disease
course to design future treatment trials. The study will utilize data obtained predominantly
from chart review. The goal is to enroll 100 participants, which include both living and
deceased individuals with GACI or ARHR2, and/or their parents and siblings. Our study will be
jointly and collaboratively conducted by the NIH and Inozyme.
- INCLUSION & EXCLUSION CRITERIA:
Based upon study purpose, participants enrolled in this protocol must:
1. Have genetic confirmation of one of the following:
1. GACI due to ENPP1 or ABCC6 mutations
2. ARHR2 due to ENPP1 mutations
3. PXE due to ABCC6 or ENPP1 mutations
2. Carry the clinical diagnosis of GACI, ARHR2 or PXE
3. Consent or, if applicable, assent to participate in the study
4. Have sufficient chart information to allow for the completion of at least one of the
protocol s objectives.
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
301-496-2563
Phone: 800-411-1222
National Institutes of Health Clinical Center The National Institutes of Health (NIH) Clinical Center in...
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