Study of People With Generalized Arterial Calcification of Infancy (GACI) or Autosomal Recessive Hypophosphatemic Rickets Type 2 (ARHR2)

NCT03478839 | Completed

• 2 other identifiers: 18006418-HG-0064
• Study Type: observational
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Generalized Arterial Calcification of Infancy; Autosomal Recessive Hypophosphatemic Rickets Type2

Keywords

Generalized Arterial Calcification of Infancy; Autosomal Recessive Hypophosphatemic Rickets; Pseudoxanthoma Elasticum; Idiopathic Infantile Arterial Calcification; Natural History

Outcome Measures

Primary Outcomes (1)

• Natural History

  The main objective of this study is to determine the natural history of patients with GACI or ARHR2.

  ongoing

Study Arms (1)

CRF completion

Individuals with a diagnosis of GACI or ARHR2 with sufficient chart data to be included in the study will be eligible for enrollment, as well as all their siblings and parents.

Eligibility Criteria

• Age: 1 Year - 110 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Individuals with a diagnosis of GACI or ARHR2 who are males or females with sufficient chart data to be included in the study will be eligible for enrollment, as well as all their male and female siblings and both parents.@@@

You may not qualify if:

• Based upon study purpose, participants enrolled in this protocol must:
• Have genetic confirmation of one of the following:
• GACI due to ENPP1 or ABCC6 mutations
• ARHR2 due to ENPP1 mutations
• PXE due to ABCC6 or ENPP1 mutations
• AND/OR
• Carry the clinical diagnosis of GACI, ARHR2 or PXE
• Consent or, if applicable, assent to participate in the study
• Have sufficient chart information to allow for the completion of at least one of the protocol s objectives.

Sponsors & Collaborators

• National Human Genome Research Institute (NHGRI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Albright RA, Stabach P, Cao W, Kavanagh D, Mullen I, Braddock AA, Covo MS, Tehan M, Yang G, Cheng Z, Bouchard K, Yu ZX, Thorn S, Wang X, Folta-Stogniew EJ, Negrete A, Sinusas AJ, Shiloach J, Zubal G, Madri JA, De La Cruz EM, Braddock DT. ENPP1-Fc prevents mortality and vascular calcifications in rodent model of generalized arterial calcification of infancy. Nat Commun. 2015 Dec 1;6:10006. doi: 10.1038/ncomms10006.

  PMID: 26624227 BACKGROUND

• Ziegler SG, Gahl WA, Ferreira CR. Generalized Arterial Calcification of Infancy. 2014 Nov 13 [updated 2020 Dec 30]. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK253403/

  PMID: 25392903 BACKGROUND

• Rutsch F, Boyer P, Nitschke Y, Ruf N, Lorenz-Depierieux B, Wittkampf T, Weissen-Plenz G, Fischer RJ, Mughal Z, Gregory JW, Davies JH, Loirat C, Strom TM, Schnabel D, Nurnberg P, Terkeltaub R; GACI Study Group. Hypophosphatemia, hyperphosphaturia, and bisphosphonate treatment are associated with survival beyond infancy in generalized arterial calcification of infancy. Circ Cardiovasc Genet. 2008 Dec;1(2):133-40. doi: 10.1161/CIRCGENETICS.108.797704.

  PMID: 20016754 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Arterial calcification of infancy; Hypophosphatemic Rickets, Autosomal Recessive, 1; Pseudoxanthoma Elasticum

Condition Hierarchy (Ancestors)

Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Skin Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases, Genetic; Genetic Diseases, Inborn; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Study Officials

• Carlos R Ferreira Lopez, M.D.

  National Human Genome Research Institute (NHGRI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2018
• First Posted: March 27, 2018
• Study Start: April 17, 2018
• Primary Completion: December 31, 2020
• Study Completion: December 31, 2020
• Last Updated: March 31, 2026

Record last verified: 2025-07-07

Locations

US (1)