Background
Clinical diagnosis of neonatal cholestasis is considered to be an extremely challenging process. Here we highlight the importance not only of the prompt distinction between extrahepatic and intrahepatic cholestasis forms, but also of the precise identification of the latter ones amongst the hotchpotch of recently discovered metabolic/genetic causes.
Biliary atresia is considered a surgical emergency in a newborn infant. The rate of success in establishing the bile drainage is in fact a function of the early age when the hepato-portoenterostomy intervention is performed. Intrahepatic cholestasis is due to a broad and more and more puzzling variety of infectious, endocrine, genetic, metabolic and toxic disorders where Gamma-glutamyl transpeptidase serum levels may help for differential diagnosis. Recently established laboratory diagnostic techniques have allowed to discover new causes of neonatal cholestasis. Aim of the Commentary is to go through some of them and bring the focus particularly on the information deriving from the paper by Pinon et al. in this issue of the Journal, which paves the way to the inclusion of the hepatocyte nuclear factor-1-beta deficiency as a new condition to consider in the diagnostic process of the syndromic forms with paucity of intralobular bile ducts.
Conclusion
Neonatal cholestasis poses diagnostic challenges in practice. Recent advances in the pathophysiology and in molecular genetics together with clinical features, histopathologic findings and careful reasoning remains paramount to put together the pieces of the jigsaw.
In presence of a residual enzyme activity, clinical features are less severe and the patients usually show hepatomegaly, raised aminotransferase serum levels, high serum levels of triglycerides Abstract Background: While a total Lysosomal Acid Lipase activity deficiency determines Wolman Disease, in partial deficiency there's a residual enzyme activity. Onset and clinical features of partial LAL-d are very variable. Secondary LAL-d has been found in patients with non alcoholic fatty liver disease obesity related. The aim of this study was to evaluate Lysosomal Acid Lipase activity (LAL-A) deficiency determined by dried blood spotting (DBS) in pediatric patients with known and unknown liver disease in order to clarify the role of this test in pediatric clinical practice. Relationship between LAL-A and liver enzymes, dyslipidemia and other parameters of metabolic syndrome was investigated.
Results:We evaluated 51 patients (36 males) with a median age of 13 years, 25 subjects with a liver disease of unknown origin and 26 with a known liver disease. LAL-A was determined by DBS on filter paper; specific genetic analysis was performed in patients with LAL-A less then the lower limit of normal. No patient resulted affected by genetically determined LAL deficiency. A low LAL-A at DBS was found in 11 (22%) patients (8 males) with variable reduction of enzymatic activity from 15% to 50% of the lower limit of normal. On ultrasound, liver steatosis was found in all patients with LAL deficiency. A significant inverse correlation between LAL-A and age of patients, triglycerides and uric acid serum levels was found. Low LAL-A subjects had significantly higher triglycerides and uric acid levels than normal one. Finally, Wilson Disease (WD) patients with low LAL-A had body-mass-index, total cholesterol, triglycerides and uric acid levels higher than normal LAL-A WD patients.
Conclusion:The study shows that different liver diseases may affect LAL activity that is inversely related to the age of patients and both triglycerides and uric acid serum levels. LAL-A is reduced in a subgroup of WD patients that showed higher BMI, total cholesterol, triglycerides and uric acid levels.
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