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A rare cause of bleeding esophageal varices: Alström syndrome
Clinics and Research in Hepatology and Gastroenterology (2012) 36, e106—e107
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www.sciencedirect.com
LETTER TO THE EDITOR
A rare cause of bleeding esophageal varices: Alström syndrome Alström Syndrome (AS) is a rare genetic disease with autosomal recessive pattern. This syndrome demonstrates multisystem involvement and occurs as a result of a mutation in ALMS1 gene located in the short arm of chromosome 2. It is characterized with retinal degeneration, sensorineural hearing loss, dilated cardiomyopathy, renal failure, fibrotic lung disease, and metabolic anomalies, hypertriglycerydemia, fatty liver, insulin resistance, type 2 diabetes mellitus, and early-onset obesity. Liver cirrhosis and related bleeding of esophageal varices are quite rare in Alström Syndrome [1]. A 32-year-old male patient was hospitalized due to upper gastrointestinal bleeding following hematemesis and melena. His physical examination revealed TA: 90/60 mmHg, Pulse: 115 and tachycardia. Due to the patient having Hb: 6.6 g/dL, 3 units of erythrocyte suspension were replaced. Body weight of the patient was 80 kg, height was 160 cm, BMI was 32. Kin marriages were not present in parents. The patient who had loss of hearing and sight had conjunctival icterus, acanthosis nigricans, scoliosis, bilateral atrophic testes, micropenis (6 cm), and horizontal nystagmus. Abdominal examination revealed nonpalpable liver and spleen and closed Traube’s space. Laboratory findings were Hb: 6.6 (14—18 g/dL) WBC: 6700 (4.000—11.000 L), Plt: 74 (150—400 × 109 /L), ALT: 75 (7—59 IU/L), AST: 229 (5—40 IU/L), ALP: 158 (38—126 IU/L), GGT: 107 (8—78 IU/L), total protein: 6.3 (6.1—8.4 g/dL), Albumin: 1.9 (3.5—5 g/dL), PT: 17.1 (13—16 seconds), and INR: 1.44. Other laboratory tests of the patient were normal. The conducted examinations demonstrated that the patient had mixed type hearing loss. Bilateral posterior subcapsular cataract and retinitis pigmentosa were detected. Mild mental retardation was established. In his abdominal ultrasonography, liver parenchymal structure had a minimal coarse and heterogeneous appearance. Spleen was approximately 14 cm. Free fluid was present between perihepatic region and intestinal loops in abdomen. Three Grade 4 varix colon and portal gastropathy was observed in esophagus in gastroesophageal endoscopy. Hemostatic values of the patient were not obtained due to
unsuitability to liver biopsy. Diagnosis is frequently made clinically as genetic test is both expensive and only conducted in limited number of centers. Our patient was diagnosed with Alström Syndrome with his current clinical picture. AS is a rare syndrome that occurs due to a mutation in ALMS-1 gen and demonstrates multisystem involvement. Metabolic anomalies, hypertriglyceridemia, insulin resistance, and type 2 diabetes mellitus are related with common obesity occurring at early ages. Generally, elevated plasma liver enzyme is detected in early childhood period. However, hepatic failure mostly occurs in 2nd or 3rd decade [2,3]. Liver involvement was first defined in Alström Syndrome by Connolly et al. In a study by Marshall et al., 92% of the patients had mild and severe elevated liver enzyme, 23% had swollen fatty liver, and 9% had portal hypertension resulted from esophagus and gastric variceal hemorrhage (age range 14-37). In addition, development of cirrhosis was observed in three patients with fatty liver and nonspecific hepatitis in literature. These patients were above the age of 40, obese, and had hypertriglyceridemia [1,3,4]. The reason for liver cirrhosis was not completely clarified in this syndrome. However, severe steatohepatitis that has an onset in early childhood causes the development of liver cirrhosis in advanced ages in AS. Complying with literature, our patient had portal hypertension and esophageal variceal bleeding as liver complications in the 3rd decade. Consequently, in literature, severe steatohepatitis at early ages and liver cirrhosis and portal hypertension at advanced ages are developed in Alström Syndrome. Esophageal variceal bleeding that is a severe complication of AS liver cirrhosis is quite rare. It must be borne in mind that the etiology of liver cirrhosis patients with obese at young ages, diabetes mellitus and retinal degeneration and presenting to clinic with bleeding esophageal varices may have also Alström Syndrome.
Disclosure of interest The authors declare that they have no conflicts of interest concerning this article.
2210-7401/$ – see front matter © 2012 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.clinre.2012.03.012
A rare cause of bleeding esophageal varices: Alström syndrome
References [1] Connolly MB, Jan JE, Couch RM, et al. Hepatic dysfunction in Alström syndrome. Am J Med Genet 1991;40:421—4. [2] Quiros-Tejeira RE, Vargas J, Ament ME. Early-onset liver disease complicated with acute liver failure in Alström syndrome. Am J Med Genet 2001;10:9—11. [3] Marshall JD, Bronson RT, Collin GB, et al. New Alström syndrome phenotypes based on the evaluation of 182 cases. Arch Intern Med 2005;165:675—83. [4] Awazu M, Tanaka T, Sato S, et al. Hepatic dysfunction in two sibs with Alström syndrome: case report and review of the literature. Am J Med Genet 1997;69:13—6.
e107 Erol Cakmak a,∗ Duygu Oguz Acıbucu b Ozlem Yonem a Hilmi Ataseven a a Department of Gastroenterology, Cumhuriyet University, Faculty of Medicine, 58140, Sivas, Turkey b Department of Internal Medicine, Cumhuriyet University, Faculty of Medicine, 58140, Sivas, Turkey ∗
Corresponding author. Tel.: +90 346 2580000; fax: +90 346 2581305. E-mail address: [email protected] (E. Cakmak) Available online 18 April 2012
Available online at
www.sciencedirect.com
LETTER TO THE EDITOR
A rare cause of bleeding esophageal varices: Alström syndrome Alström Syndrome (AS) is a rare genetic disease with autosomal recessive pattern. This syndrome demonstrates multisystem involvement and occurs as a result of a mutation in ALMS1 gene located in the short arm of chromosome 2. It is characterized with retinal degeneration, sensorineural hearing loss, dilated cardiomyopathy, renal failure, fibrotic lung disease, and metabolic anomalies, hypertriglycerydemia, fatty liver, insulin resistance, type 2 diabetes mellitus, and early-onset obesity. Liver cirrhosis and related bleeding of esophageal varices are quite rare in Alström Syndrome [1]. A 32-year-old male patient was hospitalized due to upper gastrointestinal bleeding following hematemesis and melena. His physical examination revealed TA: 90/60 mmHg, Pulse: 115 and tachycardia. Due to the patient having Hb: 6.6 g/dL, 3 units of erythrocyte suspension were replaced. Body weight of the patient was 80 kg, height was 160 cm, BMI was 32. Kin marriages were not present in parents. The patient who had loss of hearing and sight had conjunctival icterus, acanthosis nigricans, scoliosis, bilateral atrophic testes, micropenis (6 cm), and horizontal nystagmus. Abdominal examination revealed nonpalpable liver and spleen and closed Traube’s space. Laboratory findings were Hb: 6.6 (14—18 g/dL) WBC: 6700 (4.000—11.000 L), Plt: 74 (150—400 × 109 /L), ALT: 75 (7—59 IU/L), AST: 229 (5—40 IU/L), ALP: 158 (38—126 IU/L), GGT: 107 (8—78 IU/L), total protein: 6.3 (6.1—8.4 g/dL), Albumin: 1.9 (3.5—5 g/dL), PT: 17.1 (13—16 seconds), and INR: 1.44. Other laboratory tests of the patient were normal. The conducted examinations demonstrated that the patient had mixed type hearing loss. Bilateral posterior subcapsular cataract and retinitis pigmentosa were detected. Mild mental retardation was established. In his abdominal ultrasonography, liver parenchymal structure had a minimal coarse and heterogeneous appearance. Spleen was approximately 14 cm. Free fluid was present between perihepatic region and intestinal loops in abdomen. Three Grade 4 varix colon and portal gastropathy was observed in esophagus in gastroesophageal endoscopy. Hemostatic values of the patient were not obtained due to
unsuitability to liver biopsy. Diagnosis is frequently made clinically as genetic test is both expensive and only conducted in limited number of centers. Our patient was diagnosed with Alström Syndrome with his current clinical picture. AS is a rare syndrome that occurs due to a mutation in ALMS-1 gen and demonstrates multisystem involvement. Metabolic anomalies, hypertriglyceridemia, insulin resistance, and type 2 diabetes mellitus are related with common obesity occurring at early ages. Generally, elevated plasma liver enzyme is detected in early childhood period. However, hepatic failure mostly occurs in 2nd or 3rd decade [2,3]. Liver involvement was first defined in Alström Syndrome by Connolly et al. In a study by Marshall et al., 92% of the patients had mild and severe elevated liver enzyme, 23% had swollen fatty liver, and 9% had portal hypertension resulted from esophagus and gastric variceal hemorrhage (age range 14-37). In addition, development of cirrhosis was observed in three patients with fatty liver and nonspecific hepatitis in literature. These patients were above the age of 40, obese, and had hypertriglyceridemia [1,3,4]. The reason for liver cirrhosis was not completely clarified in this syndrome. However, severe steatohepatitis that has an onset in early childhood causes the development of liver cirrhosis in advanced ages in AS. Complying with literature, our patient had portal hypertension and esophageal variceal bleeding as liver complications in the 3rd decade. Consequently, in literature, severe steatohepatitis at early ages and liver cirrhosis and portal hypertension at advanced ages are developed in Alström Syndrome. Esophageal variceal bleeding that is a severe complication of AS liver cirrhosis is quite rare. It must be borne in mind that the etiology of liver cirrhosis patients with obese at young ages, diabetes mellitus and retinal degeneration and presenting to clinic with bleeding esophageal varices may have also Alström Syndrome.
Disclosure of interest The authors declare that they have no conflicts of interest concerning this article.
2210-7401/$ – see front matter © 2012 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.clinre.2012.03.012
A rare cause of bleeding esophageal varices: Alström syndrome
References [1] Connolly MB, Jan JE, Couch RM, et al. Hepatic dysfunction in Alström syndrome. Am J Med Genet 1991;40:421—4. [2] Quiros-Tejeira RE, Vargas J, Ament ME. Early-onset liver disease complicated with acute liver failure in Alström syndrome. Am J Med Genet 2001;10:9—11. [3] Marshall JD, Bronson RT, Collin GB, et al. New Alström syndrome phenotypes based on the evaluation of 182 cases. Arch Intern Med 2005;165:675—83. [4] Awazu M, Tanaka T, Sato S, et al. Hepatic dysfunction in two sibs with Alström syndrome: case report and review of the literature. Am J Med Genet 1997;69:13—6.
e107 Erol Cakmak a,∗ Duygu Oguz Acıbucu b Ozlem Yonem a Hilmi Ataseven a a Department of Gastroenterology, Cumhuriyet University, Faculty of Medicine, 58140, Sivas, Turkey b Department of Internal Medicine, Cumhuriyet University, Faculty of Medicine, 58140, Sivas, Turkey ∗
Corresponding author. Tel.: +90 346 2580000; fax: +90 346 2581305. E-mail address: [email protected] (E. Cakmak) Available online 18 April 2012