Natural History of GACI
Research type
Research Study
Full title
The Natural History of Generalized Arterial Calcification of Infancy (GACI) with or without autosomal recessive hypophosphatemic rickets type 2 (ARHR2) or pseudoxanthoma elasticum (PXE)
IRAS ID
242308
Contact name
Zulf Mughal
Contact email
Sponsor organisation
Münster University Hospital
Duration of Study in the UK
0 years, 8 months, 4 days
Research summary
Generalized arterial calcification of infancy (GACI) is an ultra-rare disorder characterized by extensive arterial calcifications, arterial stenosis, myointimal proliferation and periarticular calcifications. GACI is strongly associated with inactivating mutations in ectonucleotide pyrophosphate/ phosphodiesterase 1 (ENPP1); around three quarters of GACI cases investigated had one or several ENPP1 mutations. Many patients with GACI, including some without an ENPP1 mutation also present with mutations in adenosine triphosphate binding cassette transporter protein subfamily C member 6 (ABCC6). Autosomal recessive hypophosphatemic rickets type 2 (ARHR2) and pseudoxanthoma elasticum (PXE) are believed to be closely related to GACI. ARHR2 is caused by mutations in the ENPP1 gene and PXE is caused by mutations in the ABCC6 gene, with both being observed among patients with GACI. ENPP1 enzyme replacement therapy for GACI is currently under development and may in the future contribute to addressing the existing treatment gap in this devastating condition. The natural history of GACI and in particular its long term morbidity and mortality are poorly understood, but a strong understanding of the condition will be crucial for further therapy development and drug testing. This study aims to address this knowledge gap by conducting a retrospective chart review to describe the natural history of GACI with or without ARHR2/PXE. International physicians who are known to currently or previously manage patients with GACI will be asked to participate in this study. For eligible patients, data on vital status, diagnosis, mutational analysis, past medical history, initial presentation, clinical course, psychosocial development, therapy, and lab results will be retrospectively abstracted from the chart.
REC name
Yorkshire & The Humber - South Yorkshire Research Ethics Committee
REC reference
18/YH/0364
Date of REC Opinion
17 Oct 2018
REC opinion
Further Information Favourable Opinion