ADCK2 Haploinsufficiency Reduces Mitochondrial Lipid Oxidation and Causes Myopathy Associated with CoQ Deficiency.

Fatty acids and glucose are the main bioenergetic substrates in mammals. Impairment of mitochondrial fatty acid oxidation causes mitochondrial myopathy leading to decreased physical performance. Here, we report that haploinsufficiency of ADCK2, a member of the aarF domain-containing mitochondrial protein kinase family, in human is associated with liver dysfunction and severe mitochondrial myopathy with lipid droplets in skeletal muscle. In order to better understand the etiology of this rare disorder, we generated a heterozygous Adck2 knockout mouse model to perform in vivo and cellular studies using integrated analysis of physiological and omics data (transcriptomics-metabolomics). The data showed that Adck2+/- mice exhibited impaired fatty acid oxidation, liver dysfunction, and mitochondrial myopathy in skeletal muscle resulting in lower physical performance. Significant decrease in Coenzyme Q (CoQ) biosynthesis was observed and supplementation with CoQ partially rescued the phenotype both in the human subject and mouse model. These results indicate that ADCK2 is involved in organismal fatty acid metabolism and in CoQ biosynthesis in skeletal muscle. We propose that patients with isolated myopathies and myopathies involving lipid accumulation be tested for possible ADCK2 defect as they are likely to be responsive to CoQ supplementation.

Removal of a Frontal Sinus Osteoma and Reconstruction by a Custom-Made Implant with Neuronavigation Assistance.

The authors report the surgical treatment of an extensive right frontal sinus osteoma assisted by neuronavigation and reconstruction by a hydroxyapatite custom-made implant. The patient presents with ptosis, hypoglobus, and proptosis of the right eye, without any visual impairment. Computed tomographic (CT) scan showed a very large bony mass involving right frontal sinus and displacing the orbital roof. A stereolithographic model-guided planning was carried out to obtain a practical simulation of the surgical operation and it was submitted to a new CT scan to acquire the reference point to realize the neuronavigation assistance, and to achieve the template to realize the hydroxyapatite custom-made implant. Intraoperatively, with the help of neuronavigation assistance, osteotomies were performed by piezoelectric device. The reconstruction was made using a hydroxyapatite custom-made implant. The procedure was damage free, the bony mass was excised, and the orbital roof was repaired without any adverse effects. Postsurgical CT scan and scintigraphy showed a good reconstruction and a good-quality osteoblasts activity on the borders of the implant. Osteoma is a benign slow-growing bone tumor, usually involving the frontal sinus. Navigational assistance offers a very important help to perform safe osteotomies. Hydroxyapatite custom-made implant seems to be an excellent reconstructive method.