Metabolism diagnosis, biopsies

A 61-year-old woman developed symptoms of acute hepatitis 6 weeks after she began to take fluvastatin sodium 20 mg/day for hypercholesterolemia (3). Ultrasonography and liver biopsy confirmed the diagnosis of non-obstructive intrahepatic jaundice. Studies of viral markers and autoimmune factors excluded viral hepatitis and autoimmune hepatitis. There was a high serum concentration of a metabolite of fluvastatin, suggesting a possible anomaly of drug metabolism. All liver function tests normalized 8 weeks after the withdrawal of fluvastatin. 

OTC deficiency is the most common urea cycle defect.As it is X linked, affected boys typically have severe disease with neonatal presentation as described in this chapter. The disease in women who carry an OTC mutation on one X chromosome ranges from severe early-onset disease to complete absence of symptoms. Furthermore, affected women may decompensate in the context of a metabolic stress such as an infection or following parturition. OTC-deficient patients have low plasma citrulline and high urine orotic acid. Confirmation of the diagnosis requires mutation analysis or a liver biopsy for enzymology. The carrier status of women is most accurately determined by mutation analysis. 

PBC typically presents as an asymptomatic elevation of ALP, but may present with features of cholestasis or with fatigue. Metabolic bone disease and xanthomas are common complications of PBC. Occasionally, autoantibodies are detected (usually because of the presence of another autoimmune disease or because of family history of PBC) before elevation of ALP. Aminotransferase activities are increased in 50% of cases, but are more than twice the upper reference limit in only 20% of cases.Increased bilirubin is a late finding and is important in predicting decompensation. Antibodies to mitochondria or to the recombinant pyruvate decarboxylase complex appear similar in sensitivity, although the latter are more specific. A liver biopsy is not required for diagnosis in most cases, but may be helpful in those with low titer antibodies or with greater than twofold increase in aminotransferase activity. 

The remodeling process, involving continuous resorption of both the mineralized portion of bone and the organic matrix, is coupled with the formation process and must precede it. In other words, in normal bone, formation cannot occur until resorption has taken place. In recent years much has been learned about this microscopic remodeling system which operates continuously in the entire skeleton.12 Bone cells known as osteoclasts are responsible for the resorption process. Formation and mineralization are initiated by cells known as osteoblasts. Modern histomorpho-metric techniques applied to the cells and surfaces of serial bone biopsies enable researchers to detect and quantitate malfunctions underlying the pathology in various types of metabolic bone disease. With this capability the utility of these techniques in diagnosis and evaluation of treatment are obvious. 

Cirrhosis is the end point of both acute and chronic liver damage, as well as being caused by a number of metabolic and autoimmune diseases. Biochemical tests may be of little value in making a specific diagnosis. A liver biopsy is frequently more helpful. 

The strong optical contrast reflects the increased chemical diversity in different cancerous cells. The bright contrast may be due to the accumulation of metal ions and mitochondria in the rapidly replicating cells, and the dark contrast to accumulation of metabolic products. Applications to breast biopsy material for fast precancer diagnosis when the cells start with microcalcification are highly promising primarily for patients with a genetic risk. 

Whenever an exceedingly high tyrosine concentration is found, especially if it is accompanied by eye symptoms, it seems appropriate to reduce phenylalanine and tyrosine intake whether it is a transient tyrosinemia in the newborn or caused by an inherited disorder of tyrosine metabolism. Especially for tyrosinemia type II and III, positive confirmation of the diagnosis may be delayed considerably, and if a liver biopsy is considered, this should wait until persistency of the tyrosinemia has been established. 

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