Introduction: Parkinson’s disease (PD) is a prevalent neurodegenerative disorder, with several proposed pathogenic mechanisms. Given the established role of mitochondrial dysfunction in PD, this study seeks to investigate the enrichment of rare genetic variants tied to mitochondrial metabolism in cases of early-onset and familial PD. Methods: We performed a retrospective analysis on 248 early-onset and familial PD patients and 1622 control individuals. We assessed both pathway-level and gene-level burden of germline rare variants detected using exome sequencing in 467 nuclear genes related to mitochondrial metabolism. Results: Gene-set mutation burden analysis indicated an increased burden in genes associated with mtDNA maintenance. In addition, gene-level analysis identified a possible association between PD and rare variant burden in 14 mitochondrial metabolism-related genes under dominant or recessive inheritance models. Conclusions: Our findings support a potential contribution of rare germline variants affecting mitochondrial metabolism to the susceptibility in early-onset and familial PD.

Introduction: Hereditary hemorrhagic telangiectasia (HHT) also known as Osler–Weber–Rendu syndrome is a relatively common, under-recognized autosomal-dominant disorder that results from multisystem vascular dysplasia. It is characterized by telangiectasis and arteriovenous malformations of skin, mucosa, and viscera. Case Report: A 26-year-old man presented with an 8-day history of headache, fever, cough, right hemiparesis, motor dysphasia, and dysgraphia. The urgent brain computed tomography (CT) scan revealed a bulky rounded left frontal lobe lesion, with peripheral contrast enhancement and marked perilesional edema, indicating a brain abscess or metastasis. A brain magnetic resonance imaging showed an intra-axial hypovascular round enhancing left frontal lobe lesion, with pronounced perilesional edema. Laboratory findings discovered severe polycythemia with normal level of erythropoietin and gas analysis of blood revealed hypoxemia of secondary cause. Computed tomography of the lungs suggested pulmonary arteriovenous malformations (AVMs) in the right and left lung. Contrast-enhanced chest CT scan confirmed AVM of the lungs, while abdominal CT scan ruled out AVM of the liver. The brain abscess was treated neurosurgically. The patient reported positive family history of epistaxis. Conclusion: Brain abscess may be the first manifestation of HHT and early clinical recognition of HHT in patients with positive family history of epistaxis may help to prevent complications. Keywords: Arteriovenous malformations, Brain abscess, Hereditary hemorrhagic telangiectasia, Hypoxemia, Polycythemia