Gastric angiodysplasia in a hereditary hemorrhagic telangiectasia type 2 patient

Abstract

Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal-dominantly inherited disease that occurs in approximately one in 5000 to 8000 people. Clinical diagnosis of HHT is made when a person presents three of the following four criteria: family history, recurrent nosebleeds, mucocutaneous telangiectasis, and arteriovenous malformations (AVM) in the brain, lung, liver and gastrointestinal (GI) tract. Although epistaxis is the most common presenting symptom, AVMs affecting the lungs, brain and GI tract provoke a more serious outcome. Heterozygous mutations in endoglin, activin receptor-like kinase 1 (ACVRL1; ALK1), and SMAD4, the genes involved in the transforming growth factor-β family signaling cascade, cause HHT. We report here the case of a 63 year-old male patient who presented melena and GI bleeding episodes, proven to be caused by bleeding from multiple gastric angiodysplasia. Esophagogastroduodenoscopy revealed multiple angiodysplasia throughout the stomach. Endoscopic argon plasma coagulation was performed to control bleeding from a gastric angiodysplasia. The patient has been admitted several times with episodes of hemoptysis and hematochezia. One year ago, the patient was hospitalized due to right-sided weakness, which was caused by left basal ganglia hemorrhage as the part of HHT presentation. In family history, the patient's mother and elder sister had died, due to intracranial hemorrhage, and his eldest son has been suffered from recurrent epistaxis for 20 years. A genetic study revealed a mutation in exon 3 of ALK1 (c.199C > T; p.Arg67Trp) in the proband and his eldest son presenting epistaxis.

Keywords: Activin receptor-like kinase 1; Angiodysplasia; Epistaxis; Hereditary hemorrhagic telangiectasia; Intracranial hemorrhage.

Figure 1

Multiple angiodysplastic lesions were noted in the entire stomach upon endoscopic examination. A: A view of the lesser curvature of the angle showing multiple scattered angiodysplastic lesions; B: A view of the anterior wall of the antrum, magnified view of angiodysplastic lesions showing vessel-pulled appearance.

Figure 2

Pedigree and genetic analysis of an hereditary hemorrhagic telangiectasia family. A: Pedigree of a family with genetic mutations and/or symptoms of hereditary hemorrhagic telangiectasia (HHT) and intracranial hemorrhage (ICH). The proband is indicated by an arrow. A divided symbol represents the individual with ICH. Deceased individuals are indicated by a slash; B: Genetic studies of unaffected and affected family members. The affected member had a heterozygous activin receptor-like kinase 1 (ALK1) mutation (c.199C > T; p.Arg67Trp). The amino acid translation is shown above each codon. The mutation was found in exon 3, indicated by an asterisk; 3. Protein domains of ALK1 are indicated under the exons: extracellular domain (ECD), transmembrane domain (TM), and kinase domain (KD).

Figure 3

Hepatic arterio-venous shunt and cerebral hemorrhage. A: Abdominal computed tomography (CT) showing an intra-hepatic arterio-venous shunt; B: Cerebral hemorrhage was noted in the left basal ganglia on brain CT.