No abstract

Alpers-Huttenlocher syndrome (AHS) is an uncommon autosomal recessive mitochondrial DNA depletion disease. The classic clinical triad of progressive developmental regression, liver degeneration, and seizures helps define the disorder, but a wide range of clinical expressions occur. The most common mutations in childhood have been identified in the cytochrome c oxidase Ⅰ and Ⅳ genes. The 7706G˃A missense mutation in the Cox Ⅱ gene was previously reported in one case after postmortem histological study. Consequently, our patient is the first patient diagnosed with AHS with a 7706G˃A missense mutation in the Cox Ⅱ gene while alive. We proposed that 7706G˃A missense mutation is rare and should be more lethal than other mutations that cause Alpers-Huttenlocher syndrome.

Objective: Hydroxychloroquine (HCQ) has immunomodulatory, antithrombotic, cardiovascular, antimicrobial, and antineoplastic effects. In this study, we aimed to investigate antiapoptotic and immunomodulator effect of intraperitoneal HCQ in hypoxic-ischemic (HI) injury in newborn rats. Study Design: Seven to 10 days old Wistar-Albino rats were randomly divided into three groups: Hypoxic-ischemic encephalopathy (HIE) group, HIE treated with HCQ group and Sham group. Left common carotid artery ligation and hypoxia model were performed in HIE and HCQ groups. HCQ group was treated with 80 mg/kg intraperitoneal HCQ every 24 h for 3 days while Sham and HIE groups were given physiologic saline. After 72h, rats were decapitated and brain tissues were stained with hematoxylin and eosin, TUNEL and IL-1β for histopathological grading and neuronal cell injury. Results: Neuronal apoptosis was statistically lower in all neuroanatomical areas in HCQ group compared to HIE group. IL-1β stained areas were similar in both HCQ and HIE groups but significantly higher compared to the Sham group. Histopathological grading scores were found to be lower in HCQ group on the left parietal cortex and hippocampus region. Conclusion: In this study we have shown for the first time that HCQ treatment decreased apoptosis in HI newborn rat model in both hemispheres. HCQ may be a promising adjuvant theraphy in neonatal hypoxic ischemic encephalopathy. Key Words: Hydroxychloroquine, hypoxic-ischemic injury, antiapoptotic, immunomodulator, newborn.