1. Fructose‐1,6‐bisphosphatase deficiency causes fatty liver disease and requires long‐term hepatic follow‐up
- Author
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Magali Gorce, Elise Lebigot, Alina Arion, Anaïs Brassier, Aline Cano, Pascale De Lonlay, François Feillet, Claire Gay, François Labarthe, Marie‐Cécile Nassogne, Sandrine Roche, Agathe Roubertie, Elise Sacaze, Guy Touati, Pierre Broué, UCL - SSS/IONS/NEUR - Clinical Neuroscience, UCL - (SLuc) Centre de malformations vasculaires congénitales, UCL - (SLuc) Centre de référence en lésions congénitales de la moëlle épinière, UCL - (SLuc) Centre de référence pour l'épilepsie réfractaire, and UCL - (SLuc) Service de neurologie pédiatrique
- Subjects
Fructose-1,6-Diphosphatase Deficiency ,medicine.medical_specialty ,Fructose ,Hypoglycemia ,Gastroenterology ,Mice ,Liver disease ,Internal medicine ,Genetics ,medicine ,Animals ,Humans ,Transaminases ,Genetics (clinical) ,medicine.diagnostic_test ,business.industry ,Fatty liver ,acute liver failure ,medicine.disease ,6-bisphosphatase deficiency ,Fructose-Bisphosphatase ,Fatty Liver ,lactic acidosis ,Liver ,Lactic acidosis ,Liver biopsy ,bright liver ,Etiology ,fatty liver disease ,Hyperlactatemia ,fructose-1 ,Steatosis ,business ,gluconeogenesis defect ,Follow-Up Studies ,Hepatomegaly - Abstract
Liver disease, occurring during pediatric or adult age, is often of undetermined cause. Some cases are probably related to undiagnosed inherited metabolic disorders. Hepatic disorders associated with fructose-1,6-bisphosphatase deficiency, a gluconeogenesis defect, are not reported in the literature. These symptoms are mainly described during acute crises, and many reports do not mention them because hypoglycemia and hyperlactatemia are more frequently in the forefront. Herein, the liver manifestations of 18 patients affected with fructose-1,6-bisphosphatase deficiency are described and the corresponding literature is reviewed. Interestingly, all 18 patients had liver abnormalities either during follow-up (hepatomegaly [n = 8/18], elevation of transaminases [n = 6/15], bright liver [n = 7/11]) or during acute crises (hepatomegaly [n = 10/17], elevation of transaminases [n = 13/16], acute liver failure [n = 6/14], bright liver [n = 4/14]). Initial reports described cases of liver steatosis, when liver biopsy was necessary to confirm the diagnosis by an enzymatic study. There is no clear pathophysiological basis for this fatty liver disease but we postulate that endoplasmic reticulum stress and de novo lipogenesis activation could be key factors, as observed in FBP1 knockout mice. Liver steatosis may expose patients to severe long-term liver complications. As hypoglycemia becomes less frequent with age, most adult patients are no longer monitored by hepatologist. Signs of fructose-1,6-bisphosphatase deficiency may be subtle and can be missed in childhood. We suggest that fructose-1,6-bisphosphatase deficiency should be considered as an etiology of hepatic steatosis, and a liver monitoring protocol should be set up for these patients, during lifelong follow-up.
- Published
- 2021
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