C0604 - Novel Nodules: A Previously Unreported Manifestation of Aicardi-Goutières Syndrome

Monday, October 24, 2022

3:00 PM – 5:00 PM ET

Location: Crown Ballroom

Has Audio

Presenting Author(s)

Matthew Houle, MD

Tulane University
New Orleans, LA

Matthew Houle, MD¹, Eric Lorio, MD², Austin Hansen, MD¹, Martin Moehlen, MD, MPH³
¹Tulane University, New Orleans, LA; ²Tulane University, Metairie, LA; ³Tulane University School of Medicine, New Orleans, LA

Introduction: Aicardi-Goutières syndrome (AGS) is a rare autosomal recessive genetic disorder resulting from mutations of genes encoding multiple proteins, including DNA 3’ repair exonuclease 1 (TREX1). This form of leukodystrophy is characterized by increased interferon-alpha in the cerebrospinal fluid and serum leading to immune dysfunction primarily targeting white matter myelin in the brain. Late onset AGS can affect other organs, including liver, kidneys, heart, and lungs. Hepatic inflammation is associated with the neonatal form of AGS, but the incidence of hepatitis across other ages remains unknown. To our knowledge, there have been no reported cases of nodular regenerative hyperplasia in adults with Aicardi-Goutières syndrome.

Case Description/Methods: A 63-year-old man was evaluated for proteinuria and microscopic hematuria. Laboratory workup was unrevealing and renal ultrasound was normal. Family history was significant for father with kidney transplant for unknown renal disease and brother with recurrent bilateral vitreous hemorrhage. Subsequently, the patient and brother had kidney biopsies that showed findings consistent with thrombotic microangiopathy (TMA). Familial TMA prompted whole genome sequencing that revealed a mutation in TREX1 in all three family members. Following nephrology workup, the patient was incidentally found to have a nodular hepatic contour suggestive of cirrhosis. Physical exam was absent of stigmata of liver disease, and he denied a history of alcohol use. A focused laboratory workup was unrevealing (Table 1). MRCP revealed a nodular liver consistent with fibrosis and no intrahepatic or extrahepatic biliary dilation. MR elastography showed F2-F3 fibrosis without evidence of hepatic steatosis or iron overload. Ultimately, a percutaneous liver biopsy demonstrated nodular regenerative hyperplasia (NRH).

Discussion: NRH has been associated with autoimmune conditions such as systemic lupus erythematosus (SLE) and is thought to be caused by blood vessel inflammation within the liver leading to an overcompensated replication of hepatocytes. The finding of NRH in this patient is representative of the phenotypic overlap between AGS and SLE related to the common underlying feature of IFN-α up-regulation. As seen in this patient, NRH typically does not cause any overt signs or symptoms of liver disease. However, given it can eventually lead to the development of non-cirrhotic portal hypertension, further monitoring of this patient is warranted.

Figure: Figure (No 1). Percutaneous liver biopsy with nodular regenerative hyperplasia. (A, B) Liver biopsy, reticulin stain, low power x40. Focal compression of reticulin framework with alternated areas of sinusoidal dilatation which gives rise to a vague nodular appearance in the absence of fibrosis, suggestive of NRH. (C, D) Liver biopsy, H&E stain, low power x40. Intact hepatic architecture with focal hepatocyte atrophy and hepatocyte plate compression with areas of sinusoidal congestion. There is no significant hepatocyte apoptosis or necrosis. Hepatic lobules show mild reactivity with occasional lymphocytic inflammation. There is no significant steatosis, ground glass cells or viral inclusions.

AST/ALT	Total Bilirubin	Alkaline Phosphatase	Viral Hepatitis Serologies (HAV, HBV, HCV)	Serum Total Protein	Serum Albumin	Ceruloplasmin	Anti-Smooth Muscle Antibody	Alpha-Fetoprotein	Alpha-1 Antitrypsin
14/21 units/L	0.4 mg/dL	92 units/L	Non-reactive	7.4 g/dL	3.4 g/dL	24.6 mg/dL	11 units	1.0 ng/mL	126 mg/dL

Table: Table (No 1). Focused Laboratory Results.

Disclosures:

Matthew Houle indicated no relevant financial relationships.

Eric Lorio indicated no relevant financial relationships.

Austin Hansen indicated no relevant financial relationships.

Martin Moehlen indicated no relevant financial relationships.

Matthew Houle, MD¹, Eric Lorio, MD², Austin Hansen, MD¹, Martin Moehlen, MD, MPH³. C0604 - Novel Nodules: A Previously Unreported Manifestation of Aicardi-Goutières Syndrome, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.