Andreia Ribeiro1, José Ricardo Brandão2, Esmeralda Cleto3, Manuela Santos4, Teresa Borges5, Ermelinda Santos Silva1,6. 1. Gastroenterology Unit, Pediatrics Division, Child and Adolescent Department, Centro Materno Infantil do Norte, Centro Hospitalar Universitário do Porto, Porto, Portugal. 2. Anatomical Pathology Department, Hospital de Santo António, Centro Hospitalar Universitário do Porto, Porto, Portugal. 3. Hematology Unit, Pediatrics Division, Child and Adolescent Department, Centro Materno Infantil do Norte, Centro Hospitalar Universitário do Porto, Porto, Portugal. 4. Neurology Unit, Pediatrics Division, Child and Adolescent Department, Centro Materno Infantil do Norte, Centro Hospitalar Universitário do Porto, Porto, Portugal. 5. Endocrinology Unit, Pediatrics Division, Child and Adolescent Department, Centro Materno Infantil do Norte, Centro Hospitalar Universitário do Porto, Porto, Portugal. 6. Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.
Abstract
INTRODUCTION: Lipodystrophies are a heterogeneous group of rare diseases (genetic or acquired) characterized by a partial or generalized deficit of adipose tissue, resulting in less energy storage capacity. They are associated with severe endocrine-metabolic complications with significant morbidity and mortality. In the pathogenesis of the acquired forms, immunological disorders may be involved. CASE 1: A 13-year-old female was diagnosed with acquired generalized lipodystrophy and observed for suspicion of portal hypertension. She presented with generalized absence of adipose tissue, cervical and axillary acanthosis nigricans, and massive hepatosplenomegaly. Laboratory tests revealed AST 116 IU/L, ALT 238 IU/L, GGT 114 IU/L, HOMA-IR 28.2, triglycerides 491 mg/L, and leptin < 0.05 ng/mL. Upper gastrointestinal endoscopy saw no signs of portal hypertension. Hepatic histology showed macrovesicular fatty infiltration (60% of hepatocytes) and advanced fibrosis/cirrhosis. Her clinical condition worsened progressively to diabetes requiring treatment with subcutaneous insulin and hepatopulmonary syndrome. CASE 2: A 15-year-old female, diagnosed with acquired partial lipodystrophy, Parkinson syndrome, autoimmune thyroiditis, and autoimmune thrombocytopenia was observed for hypertransaminasemia since the age of 8 years. She had absence of subcutaneous adipose tissue in the upper and lower limbs and ataxia. Laboratory tests showed AST 461 IU/L, ALT 921 IU/L, GGT 145 IU/L, HOMA-IR 32.6, triglycerides 298 mg/dL, normal leptin levels, platelets 84,000/μL, IgG 1,894 mg/dL, positive anti-LKM and anti-LC-1. Hepatic histology was suggestive of autoimmune hepatitis, without steatosis. She progressed favorably under metformin and immunosuppressive treatment. CONCLUSION: Early recognition and adequate characterization of liver disease in lipodystrophies is essential for a correct treatment approach. In acquired generalized lipodystrophy, the severe endocrine-metabolic disorder, which leads to steatohepatitis with cirrhotic progression, may benefit from recombinant leptin treatment.
INTRODUCTION: Lipodystrophies are a heterogeneous group of rare diseases (genetic or acquired) characterized by a partial or generalized deficit of adipose tissue, resulting in less energy storage capacity. They are associated with severe endocrine-metabolic complications with significant morbidity and mortality. In the pathogenesis of the acquired forms, immunological disorders may be involved. CASE 1: A 13-year-old female was diagnosed with acquired generalized lipodystrophy and observed for suspicion of portal hypertension. She presented with generalized absence of adipose tissue, cervical and axillary acanthosis nigricans, and massive hepatosplenomegaly. Laboratory tests revealed AST 116 IU/L, ALT 238 IU/L, GGT 114 IU/L, HOMA-IR 28.2, triglycerides 491 mg/L, and leptin < 0.05 ng/mL. Upper gastrointestinal endoscopy saw no signs of portal hypertension. Hepatic histology showed macrovesicular fatty infiltration (60% of hepatocytes) and advanced fibrosis/cirrhosis. Her clinical condition worsened progressively to diabetes requiring treatment with subcutaneous insulin and hepatopulmonary syndrome. CASE 2: A 15-year-old female, diagnosed with acquired partial lipodystrophy, Parkinson syndrome, autoimmune thyroiditis, and autoimmune thrombocytopenia was observed for hypertransaminasemia since the age of 8 years. She had absence of subcutaneous adipose tissue in the upper and lower limbs and ataxia. Laboratory tests showed AST 461 IU/L, ALT 921 IU/L, GGT 145 IU/L, HOMA-IR 32.6, triglycerides 298 mg/dL, normal leptin levels, platelets 84,000/μL, IgG 1,894 mg/dL, positive anti-LKM and anti-LC-1. Hepatic histology was suggestive of autoimmune hepatitis, without steatosis. She progressed favorably under metformin and immunosuppressive treatment. CONCLUSION: Early recognition and adequate characterization of liver disease in lipodystrophies is essential for a correct treatment approach. In acquired generalized lipodystrophy, the severe endocrine-metabolic disorder, which leads to steatohepatitis with cirrhotic progression, may benefit from recombinant leptin treatment.
Authors: Edward D Javor; Marc G Ghany; Elaine K Cochran; Elif Arioglu Oral; Alex M DePaoli; Ahalya Premkumar; David E Kleiner; Phillip Gorden Journal: Hepatology Date: 2005-04 Impact factor: 17.425
Authors: F Alvarez; P A Berg; F B Bianchi; L Bianchi; A K Burroughs; E L Cancado; R W Chapman; W G Cooksley; A J Czaja; V J Desmet; P T Donaldson; A L Eddleston; L Fainboim; J Heathcote; J C Homberg; J H Hoofnagle; S Kakumu; E L Krawitt; I R Mackay; R N MacSween; W C Maddrey; M P Manns; I G McFarlane; K H Meyer zum Büschenfelde; M Zeniya Journal: J Hepatol Date: 1999-11 Impact factor: 25.083
Authors: I Sadaf Farooqi; Giuseppe Matarese; Graham M Lord; Julia M Keogh; Elizabeth Lawrence; Chizo Agwu; Veronica Sanna; Susan A Jebb; Francesco Perna; Silvia Fontana; Robert I Lechler; Alex M DePaoli; Stephen O'Rahilly Journal: J Clin Invest Date: 2002-10 Impact factor: 14.808
Authors: H Mosbah; B Donadille; M C Vantyghem; C Vigouroux; C Vatier; S Janmaat; M Atlan; C Badens; P Barat; S Béliard; J Beltrand; R Ben Yaou; E Bismuth; F Boccara; B Cariou; M Chaouat; G Charriot; S Christin-Maitre; M De Kerdanet; B Delemer; E Disse; N Dubois; B Eymard; B Fève; O Lascols; P Mathurin; E Nobécourt; A Poujol-Robert; G Prevost; P Richard; J Sellam; I Tauveron; D Treboz; B Vergès; V Vermot-Desroches; K Wahbi; I Jéru Journal: Orphanet J Rare Dis Date: 2022-04-19 Impact factor: 4.303