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Abstract Details

Systemic Complications and Natural History of Aicardi Goutières Syndrome
Child Neurology and Developmental Neurology
P6 - Poster Session 6 (8:00 AM-9:00 AM)
8-001
To chronicle the natural history of AGS, especially its systemic manifestations, in relation to key variables such as genotype.
Aicardi Goutières Syndrome (AGS) is a heritable interferonopathy that results in variable neurologic disability and systemic complications. Key variables (e.g., genotype, age at onset) only partially correlate with neurologic function, and little is known about their association with systemic symptoms.
Clinical data from subjects with confirmed AGS were extracted from the Myelin Disorders Biorepository Project on demographics, age of onset, and neurological and systemic complications associated with AGS. Neurologic severity was assessed using a disease-specific scale (AGS Severity Scale).
The cohort included 167 subjects of all known AGS genotypes except LSM-11. The median age of systemic onset was 0.15 years [IQR 0, 0.67], while neurological onset was 0.33 years [IQR 0.08, 0.90]. Neurologic severity correlated significantly with age of systemic symptom onset. Gastrointestinal abnormalities (n=139), dysphagia/feeding intolerance (n=124), and liver dysfunction (n=67) were the most frequent systemic symptoms and occurred early in patients’ disease course. The time to some systemic events, such as feeding tube placement and chilblains, were significantly associated with genotype (Fleming-Harrington log-rank: p=0.0002, p<0.0001, respectively), with TREX1 often having earlier median onset of events. Other events, such as glaucoma and retinopathy, were more likely to occur at different points in a patient’s life, with glaucoma more likely after the first year of life (58.3%) and retinopathy within the first year (75.0%).
AGS is a heterogeneous disease with a large systemic burden and an unmet need for natural history data, which is further amplified by new therapeutics trials. Our data highlights that the frequency and time course of systemic inflammatory events varies among AGS genotypes. Systemic symptoms largely precede neurological ones. These data show the importance of tailoring clinical screening guidelines to a patient’s age, disease onset, and genotype.
Authors/Disclosures
Amanda Jan
PRESENTER 		Mrs. Jan has nothing to disclose.
Isabella Barcelos No disclosure on file
Nicholson Modesti (The Children's Hospital of Philadelphia) No disclosure on file
Sarah Woidill Sarah Woidill has nothing to disclose.
Francesco Gavazzi, MD, MD, PhD (Children'S Hospital of Philadelphia) The institution of Dr. Gavazzi has received research support from NIH. The institution of Dr. Gavazzi has received research support from NIH, NINDS. The institution of Dr. Gavazzi has received research support from IONIS Pharmaceuticals.
David Isaacs No disclosure on file
Russell D'Aiello (Children's Hospital of Philadelphia) No disclosure on file
Anjana Sevagamoorthy No disclosure on file
Amy Pizzino (Children's Hospital of Philadelphia) No disclosure on file
Johanna Schmidt No disclosure on file
Keith Van Haren, MD (Stanford Univ Neurology) Dr. Van Haren has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Viking Therapeutics. Dr. Van Haren has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bluebirdbio. Dr. Van Haren has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Orpheris. Dr. Van Haren has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Autobahn. Dr. Van Haren has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for PRIME, Inc. The institution of Dr. Van Haren has received research support from Minoryx. The institution of Dr. Van Haren has received research support from bluebirdbio. Dr. Van Haren has a non-compensated relationship as a Board of Directors with ALD Connect that is relevant to AAN interests or activities. Dr. Van Haren has a non-compensated relationship as a Scientific Advisory Board with United Leukodystrophy Foundation that is relevant to AAN interests or activities.
Stephanie Keller, MD (Children's Healthcare of Atlanta/Emory Universit) Dr. Keller has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Applied Therpeutics. Dr. Keller has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for United Leukodystrophy Foundation. The institution of Dr. Keller has received research support from CHOP/NIH. The institution of Dr. Keller has received research support from IONIS. The institution of Dr. Keller has received research support from Biomarin. The institution of Dr. Keller has received research support from Boehring-Ingelheim.
Florian Eichler, MD (Massachusetts General Hospital) An immediate family member of Dr. Eichler has received personal compensation for serving as an employee of UpToDate. Dr. Eichler has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Atlas Venture. Dr. Eichler has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acadia Pharmaceuticals. Dr. Eichler has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Leal Therapeutics. Dr. Eichler has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Orchard Tx. Dr. Eichler has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ionis Therapeutics. The institution of Dr. Eichler has received research support from ASPA Therapeutics. The institution of Dr. Eichler has received research support from Abbvie. The institution of Dr. Eichler has received research support from Ionis Pharmaceuticals.
Lisa T. Emrick, MD (Department of Neurology & Developmental Neuroscience) Dr. Emrick has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Arkema. The institution of Dr. Emrick has received research support from Lysogene. The institution of Dr. Emrick has received research support from PTC. The institution of Dr. Emrick has received research support from Roche. The institution of Dr. Emrick has received research support from NIH.
Jamie L. Fraser, MD, PhD (Children's National Medical Center; Div. Genetics & Metabolism) The institution of Dr. Fraser has received research support from NIH.
Justine Shults No disclosure on file
Adeline Vanderver, MD, FAAN (Children'S Hospital of Philadelphia) An immediate family member of Dr. Vanderver has received personal compensation for serving as an employee of Maryland Physician Care. The institution of Dr. Vanderver has received research support from Takeda. The institution of Dr. Vanderver has received research support from Passage Bio. The institution of Dr. Vanderver has received research support from Homology. The institution of Dr. Vanderver has received research support from Eli Lilly. The institution of Dr. Vanderver has received research support from Myrtelle. The institution of Dr. Vanderver has received research support from SynaptixBio. The institution of Dr. Vanderver has received research support from PMD Foundation. The institution of Dr. Vanderver has received research support from Ionis. The institution of Dr. Vanderver has received research support from ISD . The institution of Dr. Vanderver has received research support from Boehringer-Ingelheim. The institution of Dr. Vanderver has received research support from Biogen. The institution of Dr. Vanderver has received research support from Sana. The institution of Dr. Vanderver has received research support from Affinia. The institution of Dr. Vanderver has received research support from BridgeBio. The institution of Dr. Vanderver has received research support from Orchard. The institution of Dr. Vanderver has received research support from Minoryx. The institution of Dr. Vanderver has received research support from Forge Biologics. The institution of Dr. Vanderver has received research support from Vigil. Dr. Vanderver has received intellectual property interests from a discovery or technology relating to health care. Dr. Vanderver has received intellectual property interests from a discovery or technology relating to health care.
Laura A. Adang, MD Dr. Adang has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Orchard Therapeutics.