Hereditary spastic paraplegias (HSP) are a heterogeneous group of motor neurodegenerative disorders that have the core clinical presentation of pyramidal syndrome which starts typically in the lower limbs. They can present as pure or complex forms with all classical modes of monogenic inheritance reported. To date, there are more than 100 loci/88 spastic paraplegia genes (SPG) involved in the pathogenesis of HSP. New patterns of inheritance are being increasingly identified in this era of huge advances in genetic and functional studies. A wide range of clinical symptoms and signs are now reported to complicate HSP with increasing overall complexity of the clinical presentations considered as HSP. This is especially true with the emergence of multiple HSP phenotypes that are situated in the borderline zone with other neurogenetic disorders. The genetic diagnostic approaches and the utilized techniques leave a diagnostic gap of 25% in the best studies. In this review, we summarize the known types of HSP with special focus on those in which spasticity is the principal clinical phenotype (“SPGn” designation). We discuss their modes of inheritance, clinical phenotypes, underlying genetics, and molecular pathways, providing some observations about therapeutic opportunities gained from animal models and functional studies. This review may pave the way for more analytic approaches that take into consideration the overall picture of HSP. It will shed light on subtle associations that can explain the occurrence of the disease and allow a better understanding of its observed variations. This should help in the identification of future biomarkers, predictors of disease onset and progression, and treatments for both better functional outcomes and quality of life.

Background: Intellectual disability is a form of neurodevelopmental disorders that begin in childhood and is characterized by substantial intellectual difficulties as well as difficulties in conceptual, social, and practical areas of living. Several genetic and nongenetic factors contribute to its development; however, its most severe forms are generally attributed to single-gene defects. Highthroughput technologies and data sharing contributed to the diagnosis of hundreds of single-gene intellectual disability subtypes.

Introduction: Hereditary spastic paraplegia is a clinically and genetically heterogeneous neurological entity that includes more than 80 disorders which share lower limb spasticity as a common feature. Abnormalities in multiple cellular processes are implicated in their pathogenesis, including lipid metabolism; but still 40% of the patients are undiagnosed. Our goal was to identify the disease-causing variants in Sudanese families excluded for known genetic causes and describe a novel clinico-genetic entity.Methods: We studied four patients from two unrelated consanguineous Sudanese families who manifested a neurological phenotype characterized by spasticity, psychomotor developmental delay and/or regression, and intellectual impairment. We applied next-generation sequencing, bioinformatics analysis, and Sanger sequencing to identify the genetic culprit. We then explored the consequences of the identified variants in patients-derived fibroblasts using targeted-lipidomics strategies.Results and Discussion: Two homozygous variants in ABHD16A segregated with the disease in the two studied families. ABHD16A encodes the main brain phosphatidylserine hydrolase. In vitro, we confirmed that ABHD16A loss of function reduces the levels of certain long-chain lysophosphatidylserine species while increases the levels of multiple phosphatidylserine species in patient's fibroblasts.Conclusion:ABHD16A loss of function is implicated in the pathogenesis of a novel form of complex hereditary spastic paraplegia.

Coronavirus 2019 (COVID-19) is considered one of the most significant medical pandemics of this century, with high morbidity and mortality associated with the pandemic. The virus was recognized initially as a cause of pneumonia, but subsequent studies showed significant association with gastrointestinal, neurological, and autoimmune diseases. By 2020, several vaccines became available for use, significantly reducing the infection rate. A good safety profile supported most of the studies related to vaccines. However, this area is still under study, and some reports linked the COVID-19 vaccine to the development of thrombocytopenia, thrombosis, Guillain-Barre syndrome, autoimmune diseases, and myocarditis. These side effects need to be reported to VAERS (Vaccine Adverse Event Reporting System). The exact etiology of anti-glomerular basement (Anti-GBM) disease remains unknown, but the disease is thought to be triggered by environmental factors in genetically predisposed individuals. It is considered one of the serious diseases that could lead to permanent kidney impairment if not treated early and adequately. That's why a great effort is being made by health care practitioners to figure out and avoid the risk and triggering factors. Few previously published papers linked the COVID-19 vaccine and the development of anti-GBM disease, which raised concerns about digging more into this area.Herein, we are reporting a case of a patient who developed rapidly progressive glomerulonephritis (RPGN) due to anti-glomerular basement membrane (GBM) antibody disease two days after receiving the second dose of the COVID-19 vaccine.

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