Acute severe encephalopathy related to human herpesvirus-6 infection in a patient with carnitine palmitoyltransferase 2 deficiency carrying thermolabile variants.

We describe a male infant with carnitine palmitoyltransferase 2 (CPT2) deficiency who presented with acute encephalopathy related to human herpesvirus-6 (HHV-6) infection. He was hospitalized for pylexia and status epilepticus, diagnosed with acute encephalopathy, and treated with intensive supportive care including mechanical ventilation, support for hypothermia, and control of the intracranial pressure, that caused severe neurological sequelae. HHV-6 was detected in his cerebrospinal fluid, indicating HHV-6 related encephalopathy. In the acute phase, acylcarnitine analysis of blood suggested a defect of long chain fatty acid ß-oxidation, and CPT2 deficiency was genetically confirmed. In addition, other gene alterations that have been previously reported as "thermolabile variants" were found. Some patients with the infantile form of CPT2 deficiency present with acute encephalopathy, but others do not develop encephalopathy. The correlation between phenotype and genotype has not been clarified. Our case may contribute to the elucidation of the genetic factor involved in acute encephalopathy in CPT2 deficiency.

Laser captured hepatocytes show association of butyrylcholinesterase gene loss and fibrosis progression in hepatitis C-infected drug users.

UNLABELLED: Chronic hepatitis C virus (HCV) infection is complicated by hepatic fibrosis. Hypothesizing that early fibrogenic signals may originate in cells susceptible to HCV infection, hepatocyte gene expression was analyzed from persons with chronic HCV at different stages of liver fibrosis. Four HCV-infected subjects with precirrhosis liver fibrosis (Ishak fibrosis 3-5) were matched for age, race, and gender to five HCV-infected subjects with no evidence of fibrosis (Ishak fibrosis 0). Hepatocytes from each subject were isolated from liver biopsies using laser capture microdissection. Transcriptome profiling was performed on hepatocyte RNA using hybridization arrays. We found that hepatocytes in precirrhosis fibrosis were depleted for genes involved in small molecule and drug metabolism, especially butyrylcholinesterase (BCHE), a gene involved in the metabolism of drugs of abuse. Differential expression of BCHE was validated in the same tissues and cross-sectionally in an expanded cohort of 143 HCV-infected individuals. In a longitudinal study, serum BCHE activity was already decreased at study inception in 19 fibrosis progressors compared with 20 fibrosis nonprogressors (P < 0.05). Nonprogressors also had decreased BCHE activity over time compared with initial values, but these evolved a median (range) 8.6 (7.8-11.4) years after the study period inception (P < 0.05). Laser captured portal tracts were enriched for immune related genes when compared with hepatocytes but precirrhosis livers lost this enrichment. CONCLUSION: Chronic HCV is associated with hepatocyte BCHE loss years before hepatic synthetic function is impaired. These results indicate that BCHE may be involved in the pathogenesis of HCV-related fibrosis among injection drug users.