Liver Disease

Abstract

Liver pathology is an important and common sequel of inherited metabolic diseases. It is the central metabolic organ; so defects in any of the following pathways of intermediary metabolism can lead to significant liver disease: degradation of fatty acids, fructose, galactose, and glycogen as well as of gluconeogenesis, ketogenesis, urea cycle including citrin deficiency, and oxidative phosphorylation. Symptomatology may be directly linked to the pathway affected; specific symptoms reflecting the demand on the pathway may lead to diagnosis. A detailed history, as well as pathological alterations of blood ammonia, glucose, lactate, ketone bodies, and pH, can lead the path. Specific metabolic symptoms can however be obscured by consequences of rather nonspecific responses of the liver to hepatocellular damage, decreased liver function, cholestasis, and hepatomegaly.

Inherited diseases interfering primarily with hepatic cell integrity are Wilson disease, tyrosinemia type I, transaldolase deficiency, RALF syndrome caused by mutations in NBAS, cystic fibrosis, α-1-antitrypsin deficiency, and deficiencies of biosynthetic pathways, such as cholesterol biosynthesis, bile acid synthesis, peroxisomal disorders, and CDG syndromes. Very striking physical involvement of the liver with mostly relatively little functional derangement is seen in lysosomal storage disorders.

The diagnostic evaluation of liver disease must be broad, especially in neonates, and initiated early. Infectious, immunological, metabolic, and genetic causes must all be thought of and sometimes pursued in parallel. Successful outcome depends very much on early institution of specific therapy. In addition to the increasing therapeutic options for individual metabolic disorders, pediatric liver transplantation has developed into a well-established procedure, with the best outcome rates of ≥90 % in liver-based metabolic disorders.