NON-ALCOHOLIC FATTY LIVER DISEASE ASSOCIATED WITH HYPOBETALIPOPROTEINEMIA: REPORT OF THREE CASES AND A NOVEL MUTATION IN APOB GENE

  • Joana Rodrigues Pediatric Department, Centro Hospitalar Entre o Douro e Vouga
  • Ana Azevedo Pediatric Department, Centro Hospitalar Entre o Douro e Vouga
  • Susana Tavares Pediatric Department, Centro Hospitalar Entre o Douro e Vouga
  • Cristina Rocha Pediatric Department, Centro Hospitalar Entre o Douro e Vouga
  • Ermelinda Santos Silva Pediatric Gastroenterology Departament, Centro Materno-Infantil do Norte, Centro Hospitalar do Porto
Keywords: APOB gene, Children, Familial hypobetalipoproteinemia, Non-alcoholic fatty liver disease, Nonalcoholic steatohepatitis

Abstract

Background: Non-alcoholic fatty liver disease, the leading cause of chronic liver disease in children, is defined by hepatic fat infiltration >5% of hepatocytes, in the absence of excessive alcohol intake, evidence of viral, autoimmune or drug-induced liver disease. Conditions like rare genetic disorders must be considered in the differential diagnosis.

Case Report: Two male brothers, and a non-related girl, all overweight, had liver steatosis. One of the brothers and the girl had elevated transaminases; all three presented with low total cholesterol, low density lipoproteins and very low density lipoproteins cholesterol levels, hypotriglyceridemia and low apolipoprotein B. A liver biopsy performed in the brother with citolysis confirmed steatohepatitis and the molecular study of apolipoprotein B gene showed a novel homozygous mutation (c.9353dup p.Asn3118Lysfs17). Patients with cytolysis lost weight, however liver steatosis persists.

Conclusion: Fatty liver disease might be a consequence of hypobetalipoproteinemia. Evidence is scarce due to low number of reported cases.

References

Kneeman JM, Misdraji J, Corey KE (2012). Secondary causes

of non-alcoholic fatty liver disease. Therap Adv Gastroenterol.

; 5:199 - 207. doi:10.1177/1756283X11430859.

Vajro P, Lenta S, Socha P, Dhawan A, McKiernan P, Baumann

U, et al (2012). Diagnosis of nonalcoholic fatty liver disease

in children and adolescents: position paper of the ESPGHAN

Hepatology Committee. J Pediatr Gastroenterol Nutr. 2012;

:700-713 doi:10.1097/MPG.0b013e318252a13f.

Labrecque DR, Abbas Z, Anania F, Ferenci P, Khan AG,

Goh KL, et al (2014). World Gastroenterology Organisation

Global Guidelines Nonalcoholic Fatty Liver Disease and

Nonalcoholic Steatohepatitis. J Clin Gastroenterol. 2014;

:467-473 doi:10.1097/MCG.0000000000000116.

Giorgio V, Prono F, Graziano F, Nobili V (2013) Pediatric

non alcoholic fatty liver disease: old and new concepts

on development, progression, metabolic insight and

potential treatment targets. BMC Pediatr. 2013; 13:40

doi:10.1186/1471-2431-13-40.

Sen D, Dagdelen S, Erbas T (2007) Hepatosteatosis with

hypobetalipoproteinemia. J Natl Med Assoc. 2007; 99:284-6.

Lam MCW, Singham J, Hegele RA, Riazy M, Hiob MA, Francis

G, et al (2012). Familial hypobetalipoproteinemia-induced

nonalcoholic steatohepatitis. Case Rep Gastroenterol 6:429-

doi:000339761.

Schonfeld G (2003) Familial hypobetalipoproteinemia: a

review. J Lipid Res. 2003; 44:878-883 doi:10.1194/jlr.

R300002-JLR200.

Lee J, Hegele R (2014) Abetalipoproteinemia and

homozygous hypobetalipoproteinemia: a framework for

diagnosis and management. J. Inherit. Metab. Dis. 2014; 37:

-339 doi: 10.1007/s10545-013-9665-4.

Whitfield A, Barrett P, Bockxmeer F, Burnett J (2004)

Lipid Disorders and Mutations in the APOB gene. Clinical

Chemistry. 2004; 50: 1725-32.

Noto D, Cefalu AB, Barraco G, Fayer F, Minà M, Yue P,

et al (2011). Plasma non-cholesterol sterols in primary

hypobetalipoproteinemia. Atherosclerosis. 2011; 216:409-

doi:10.1016/j.atherosclerosis.2010.10.050.

Alvarez F, Berg PA, Bianchi FB, Bianchi L, Burroughs AK,

Cancado EL, et al (1999). International Autoimmune Hepatitis

Group Report: review of criteria for diagnosis of autoimmune

hepatitis. J Hepatol. 1999; 31: 929-38.

EASL Clinical Practice Guidelines: Wilson’s disease (2012) J

Hepatol. 2012; 56:671-685 doi:10.1016/j.jhep.2011.11.007.

Wu J, Kim J, Li Q, Kwok PY, Cole TG, Cefalu B, et al (1999).

Known mutations of apoB account for only a small minority

of hypobetalipoproteinemia. J Lipid Res. 1999; 40:955-9.

Gutierrez-Cirlos C, Ordonez-Sanchez ML, Tusie-Luna MT,

Patterson BW, Schonfeld G, Aguilar-Salinas CA (2011)

Familial hypobetalipoproteinemia in a hospital survey:

genetics, metabolism and non-alcoholic fatty liver disease.

Ann Hepatol. 2011; 10:155-164.

Published
2016-06-21
How to Cite
Rodrigues, J., Azevedo, A., Tavares, S., Rocha, C., & Silva, E. S. (2016). NON-ALCOHOLIC FATTY LIVER DISEASE ASSOCIATED WITH HYPOBETALIPOPROTEINEMIA: REPORT OF THREE CASES AND A NOVEL MUTATION IN APOB GENE. NASCER E CRESCER - BIRTH AND GROWTH MEDICAL JOURNAL, 25(2), 104 - 107. https://doi.org/10.25753/BirthGrowthMJ.v25.i2.9524
Section
Case Reports