Newly Recognized Hepatic Lysosomal Storage Disorder Affecting Young Children
GW Mierau, EP Wartchow, AD Segura, LS Finn. The Children's Hospital, Denver, Aurora, CO; Children's Hospital of Wisconsin, Milwaukee, WI; Seattle Children's Hospital, Seattle, WA
Background: A number of therapeutic agents (amiodarone, chloroquine, 4,4'-diethylaminoethoxyhexestrol, fluoxetine, gentamicin, perhexiline, tilorone) have been shown sometimes to produce lysosomal inclusions closely mimicking those associated with primary metabolic storage diseases. All such drug-induced inclusions described to date have presented either as membranous phospholipid whorls or as vesicles containing an amorphous flocculent material. We describe a third form of presumably drug-induced inclusion observed within the Kupffer cells of children.
Design: Electron microscopic examination of liver biopsy specimens from four children with complex incompletely defined medical conditons, ranging in age from 2 to12 years, was performed in an attempt to determine a cause for their hepatomegaly. All were experiencing chronic nutritional, immunologic, and infectious problems that had required a variety of drugs for control, and none exhibited clinical features suggestive of a primary metabolic storage disease.
Results: Observed within the Kupffer cells were multiple large irregularly shaped membrane bound inclusions packed with relatively small caliber (∼25-35 nm) slightly curvilinear tubular structures. These inclusions do not correspond precisely in appearance to those of any known primary metabolic storage disease but are vaguely reminiscent of those associated with the late-infantile variant of neuronal ceroid lipofuscinosis.
Conclusions: The described inclusions are likely the product of a secondary storage phenomenon induced by an as yet unidentified therapeutic agent. Awareness of the existence of this type of inclusion may in some cases enable a costly diagnostic workup for a nonexistent genetic disease to be averted.
Wednesday, March 24, 2010 9:30 AM
Poster Session V # 257, Wednesday Morning