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Abstract Background Zellweger spectrum disorders (ZSDs) are a rare, heterogenous group of autosomal recessively inherited disorders characterized by reduced peroxisomes numbers, impaired peroxisomal formation, and/or defective peroxisomal functioning. In the absence of functional peroxisomes, bile acid synthesis is disrupted, and multisystem disease ensues with abnormalities in the brain, liver, kidneys, muscle, eyes, ears, and nervous system. Main body Liver disease may play an important role in morbidity and mortality, with hepatic fibrosis that can develop as early as the postnatal period and often progressing to cirrhosis within the first year of life. Because hepatic dysfunction can have numerous secondary effects on other organ systems, thereby impacting the overall disease severity, the treatment of liver disease in patients with ZSD is an important focus of disease management. Cholbam® (cholic acid), approved by the U.S. Food and Drug Administration in March 2015, is currently the only therapy approved as adjunctive treatment for patients with ZSDs and single enzyme bile acid synthesis disorders. This review will focus on the use of CA therapy in the treatment of liver disease associated with ZSDs, including recommendations for initiating and maintaining CA therapy and the limitations of available clinical data supporting its use in this patient population. Conclusions Cholbam is a safe and well-tolerated treatment for patients with ZSDs that has been shown to improve liver chemistries and reduce toxic bile acid intermediates in the majority of patients with ZSD. Due to the systemic impacts of hepatic damage, Cholbam should be initiated in patients without signs of advanced liver disease.

Bile acids are synthesized by the liver from cholesterol through a complex series of reactions involving at least 14 enzymatic steps. A failure to perform any of these reactions will block bile acid production with failure to produce "normal bile acids" and, instead, result in the accumulation of unusual bile acids and intermediary metabolites. Failure to synthesize bile acids leads to reduced bile flow and decreased intraluminal solubilization of fat and fat-soluble vitamins. In some circumstances, the intermediates created because of blockade in the bile acid biosynthetic pathway may be toxic to hepatocytes. Nine recognized inborn errors of bile acid metabolism have been identified that lead to enzyme deficiencies and impaired bile acid synthesis in infants, children, and adults. Patients may present with neonatal cholestasis, neurologic disease, or fat and fat-soluble vitamin malabsorption. If untreated, progressive liver disease may develop or reduced intestinal bile acid concentrations may lead to serious morbidity or mortality. This review focuses on a description of the disorders of bile acid synthesis that are directly related to single defects in the metabolic pathway, their proposed pathogenesis, treatment, and prognosis. [ABSTRACT FROM AUTHOR]

Effective dose, a parameter utilized to assess biological risk related to radiation exposure, may be used to evaluate risk associated with dual-energy X-ray absorptiometry (DXA). We estimated the effective dose from DXA (Hologic QDR 4500A) scans of the lumbar spine (fast array mode), total body, hip (fast array mode), and forearm for children ages 1, 5, 10, and 15 yr and for adults. Entrance dose incorporating backscatter was determined for each scan type. Depth-dose curves were derived using Plexiglas slabs simulating tissue attenuation. Organ depth was estimated using pediatric phantom models. For all scan types, the effective dose decreased as age increased. The effective dose values for a 1-yr-old and an adult, respectively, were 4.7 ΜSv and 2.2 ΜSv for a lumbar spine scan performed in fast array mode, 3.4/3.5 ΜSv and 1.8/2.1 ΜSv (male/female) for a total body scan, and 0.14 ΜSv and 0.03 ΜSv for a forearm scan. There were marked sex differences in the effective dose associated with hip scans (fast array mode) ranging from 15.2 ΜSv for a 1-yr-old male to 4.6 ΜSv for an adult female. A comprehensive uncertainty analysis indicated that the effective dose values were reliable within a factor of 3. With the exception of the hip scans in 1- and 5-yr-olds, the effective doses were below the negligible individual dose limit of 10 ΜSv/yr. [ABSTRACT FROM AUTHOR]