INCIDENCE OF HEPATIC ABNORMALITIES IN INDIVIDUALS WITH PRADER-WILLI SYNDROME 

Scheimann AO^*, Moser AB^**, Lee PD⁺, LaFuente N^$, Thomas J^$, Phillips S^$, Orellana D^$, Hayslett BH^$, Gordon B^$, Klish WJ^$. 

AFFILIATIONS:

^* Division of Pediatric Nutrition and Gastroenterology, Johns Hopkins Hospital, Baltimore, MD

^** Peroxisomal Disease Laboratory, Kennedy Krieger Institute, Baltimore, MD

⁺ Division of Pediatric Endocrinology, University of California-Los Angeles, Los Angeles, CA

^$ Division of Pediatric Nutrition and Gastroenterology, Baylor College of Medicine, Houston, TX

 Introduction: Population -based surveys suggest that non-alcoholic fatty liver disease is the most common form of liver disease within the United States and other industrialized nations.    Strauss, et al., utilizing NHANES III data, noted elevated ALT levels in 7.8-10.8% of obese school children and 14-16% of obese adolescents.  Baldridge, et al., found a 12.6% incidence of biopsy-proven hepatic steatosis during a 3 year retrospective review of 659 liver biopsies; 92.8% of the pediatric obese patients biopsied for non-alcoholic fatty liver disease (NAFL) had moderate to severe hepatic fibrosis upon tissue examination.  NAFL is commonly encountered in individuals with obesity, diabetes, and dyslipidemias suggesting that common hormonal or metabolic abnormalities may provide the primary trigger for development of steatosis.  In mice, genetic abnormalities which alter the balance between mitochondrial and peroxisomal β-oxidation of fatty acids also lead to hepatic steatosis and steatohepatitis.

Materials and methods: Retrospective chart review of all patients with the diagnosis of Prader-willi syndrome followed in the Prader-willi syndrome clinic for prior hepatic screening. 

Results:  A total of 29 (36%) patients (58.6% male) out of a clinic population of 81 individuals with Prader-willi syndrome had either prior liver enzyme determination, sonography or liver biopsy performed.  The average BMI % was 91% for the entire group.  The average % body fat as determined by Total Body Electrical Conductivity was 39.8%.  The average HgbA₁C for the group was 6.4%.

 55% of patients (16) had normal liver enzymes (ALT, AST, GGT);   87.5% of the patients with normal liver enzymes did not have an abdominal ultrasound performed. 1 patient with normal liver enzymes had evidence for hepatic steatosis at the time of sonography.

45% of patients (13) had abnormal liver enzymes (ALT, AST, and/or GGT).  6 out of the 13 patients had an abdominal ultrasound performed revealing fatty infiltration of the liver.  2 out of the 13 patients had gallstones detected requiring cholescystectomy with liver biopsy revealing steatohepatitis. 

Conclusion:  Individuals with Prader-willi syndrome appear to have an increased incidence of elevated transaminases most likely attributed to the development of non-alcoholic liver disease. 

References:

1.  Baldridge AD, Perez-Atayde AR, Graeme-Cook F, Higgins L, Lavine JE.  Idiopathic Steatohepatitis in Childhood: A Multi-center Retrospective Study.  J Pediatr 1995; 127: 700-4.

2.  Strauss RS, Barlow SE, Dietz WH.  Prevalance of Abnormal Aminotransferase Values in Overweight and Obese Adolescents.  J Pediatr 2000; 136: 727-33.

July 2002