Familial Hypobetalipoproteinemia-Induced Nonalcoholic Steatohepatitis
Familial hypobetalipoproteinemia (FHBL) is a rare genetic disorder of lipid metabolism that is associated with abnormally low serum levels of low-density lipoprotein (LDL) cholesterol and apolipoprotein B. It is an autosomal co-dominant disorder, and depending on zygosity, the clinical manifestation...
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| Format: | Article |
| Language: | English |
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Karger Publishers
2012-07-01
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| Series: | Case Reports in Gastroenterology |
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| Online Access: | http://www.karger.com/Article/FullText/339761 |
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| author | Mindy C.W. Lam Janakie Singham Robert A. Hegele Maziar Riazy Matti A. Hiob Gordon Francis Urs P. Steinbrecher |
| author_facet | Mindy C.W. Lam Janakie Singham Robert A. Hegele Maziar Riazy Matti A. Hiob Gordon Francis Urs P. Steinbrecher |
| author_sort | Mindy C.W. Lam |
| collection | DOAJ |
| description | Familial hypobetalipoproteinemia (FHBL) is a rare genetic disorder of lipid metabolism that is associated with abnormally low serum levels of low-density lipoprotein (LDL) cholesterol and apolipoprotein B. It is an autosomal co-dominant disorder, and depending on zygosity, the clinical manifestations may vary from none to neurological, endocrine, hematological or liver dysfunction. Nonalcoholic fatty liver disease is common in persons with FHBL, however progression to nonalcoholic steatohepatitis is unusual. We describe here a patient with a novel APOB mutation, V703I, which appears to contribute to the severity of the FHBL phenotype. He had liver enzyme abnormalities, increased echogenicity of the liver consistent with steatosis, very low LDL cholesterol at 0.24 mmol/l (normal 1.8–3.5 mmol/l) and an extremely low apolipoprotein B level of 0.16 g/l (normal 0.6–1.2 g/l). APOB gene sequencing revealed him to be a compound heterozygote with two mutations (R463W and V703I). APOB R463W has previously been reported to cause FHBL. Genetic sequencing of his first-degree relatives identified the APOB V703I mutation in his normolipidemic brother and father and the APOB R463W mutation in his mother and sister, both of whom have very low LDL cholesterol levels. These results suggest that the APOB V703I mutation alone does not cause the FHBL phenotype. However, it is possible that it has a contributory role to a more aggressive phenotype in the presence of APOB R463W. |
| first_indexed | 2024-04-13T11:18:31Z |
| format | Article |
| id | doaj.art-260e8de5d6d64bb58d39bb8b2c1ded82 |
| institution | Directory Open Access Journal |
| issn | 1662-0631 |
| language | English |
| last_indexed | 2024-04-13T11:18:31Z |
| publishDate | 2012-07-01 |
| publisher | Karger Publishers |
| record_format | Article |
| series | Case Reports in Gastroenterology |
| spelling | doaj.art-260e8de5d6d64bb58d39bb8b2c1ded822022-12-22T02:48:53ZengKarger PublishersCase Reports in Gastroenterology1662-06312012-07-016242943710.1159/000339761339761Familial Hypobetalipoproteinemia-Induced Nonalcoholic SteatohepatitisMindy C.W. LamJanakie SinghamRobert A. HegeleMaziar RiazyMatti A. HiobGordon FrancisUrs P. SteinbrecherFamilial hypobetalipoproteinemia (FHBL) is a rare genetic disorder of lipid metabolism that is associated with abnormally low serum levels of low-density lipoprotein (LDL) cholesterol and apolipoprotein B. It is an autosomal co-dominant disorder, and depending on zygosity, the clinical manifestations may vary from none to neurological, endocrine, hematological or liver dysfunction. Nonalcoholic fatty liver disease is common in persons with FHBL, however progression to nonalcoholic steatohepatitis is unusual. We describe here a patient with a novel APOB mutation, V703I, which appears to contribute to the severity of the FHBL phenotype. He had liver enzyme abnormalities, increased echogenicity of the liver consistent with steatosis, very low LDL cholesterol at 0.24 mmol/l (normal 1.8–3.5 mmol/l) and an extremely low apolipoprotein B level of 0.16 g/l (normal 0.6–1.2 g/l). APOB gene sequencing revealed him to be a compound heterozygote with two mutations (R463W and V703I). APOB R463W has previously been reported to cause FHBL. Genetic sequencing of his first-degree relatives identified the APOB V703I mutation in his normolipidemic brother and father and the APOB R463W mutation in his mother and sister, both of whom have very low LDL cholesterol levels. These results suggest that the APOB V703I mutation alone does not cause the FHBL phenotype. However, it is possible that it has a contributory role to a more aggressive phenotype in the presence of APOB R463W.http://www.karger.com/Article/FullText/339761Familial hypobetalipoproteinemiaNonalcoholic steatohepatitisAPOB |
| spellingShingle | Mindy C.W. Lam Janakie Singham Robert A. Hegele Maziar Riazy Matti A. Hiob Gordon Francis Urs P. Steinbrecher Familial Hypobetalipoproteinemia-Induced Nonalcoholic Steatohepatitis Case Reports in Gastroenterology Familial hypobetalipoproteinemia Nonalcoholic steatohepatitis APOB |
| title | Familial Hypobetalipoproteinemia-Induced Nonalcoholic Steatohepatitis |
| title_full | Familial Hypobetalipoproteinemia-Induced Nonalcoholic Steatohepatitis |
| title_fullStr | Familial Hypobetalipoproteinemia-Induced Nonalcoholic Steatohepatitis |
| title_full_unstemmed | Familial Hypobetalipoproteinemia-Induced Nonalcoholic Steatohepatitis |
| title_short | Familial Hypobetalipoproteinemia-Induced Nonalcoholic Steatohepatitis |
| title_sort | familial hypobetalipoproteinemia induced nonalcoholic steatohepatitis |
| topic | Familial hypobetalipoproteinemia Nonalcoholic steatohepatitis APOB |
| url | http://www.karger.com/Article/FullText/339761 |
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