Congenital Myasthenic Syndrome Associated With SLC25A1 Gene Variant: The First Reported Case in Saudi Arabia

Abstract

We report the case of a two-year-old full-term girl of consanguineous Saudi parents, who had a history of poor sucking, hypotonia, and bilateral ptosis, as well as recurrent pediatric intensive care unit (PICU) admissions with apnea and global developmental delay and unremarkable family history. A genetic study was conducted and whole exome sequencing (WES) identified a likely pathogenic homozygous variant c.842C>T p.(Ala281Val) in the SLC25A1 gene. This finding is consistent with the genetic diagnosis of autosomal recessive combined D-2-and L-2-hydroxyglutaric aciduria (D/L-2-HGA). Genetic testing results suggested a diagnosis of congenital myasthenic syndrome (CMS) type 23 [Online Mendelian Inheritance in Man (OMIM) #618197]. CMS is a highly heterogeneous group of neuromuscular junction (NMJ) disorders clinically and genetically and compromises the safety margin required for reliable neuromuscular transmission. Fortunately, we suspected a CMS in our patient, and the initiation of management with pyridostigmine has substantially improved the patient's condition.

Mitochondrial citrate carrier SLC25A1 is a dosage-dependent regulator of metabolic reprogramming and morphogenesis in the developing heart

“…Though previous investigations have associated SLC25A1 with several diseases 24, 26, 30–32, 35 , our results here provide comprehensive new evidence that SLC25A1 also contributes to metabolic reprogramming during cardiac development. Our mouse model results show that systemic loss of SLC25A1 led to stunted embryonic growth, perinatal lethality, and an array of developmental abnormalities including cardiac structural defects.…”

“…Because partial loss of Slc25a1 in mice is sufficient to produce CHD observed in 22q11.2DS, our data position SLC25A1 as a novel 22q11.2 mitochondrial gene that contributes to the cardiac presentation of 22q11.2DS. SLC25A1 mutations underlie two rare autosomal recessive neurometabolic/neuromuscular disorders, DL-2HGA and CMS23 [30][31][32] . While cardiac disease indices are not part of the OMIM characterization of these disorders, there have been hints that SLC25A1 variants may also impact the heart.…”

“…SLC25A1 mutations underlie two rare autosomal recessive neurometabolic/neuromuscular disorders, DL-2HGA and CMS23 30–32 . While cardiac disease indices are not part of the OMIM characterization of these disorders, there have been hints that SLC25A1 variants may also impact the heart.…”

“…In humans, SLC25A1 single-gene mutations underlie two rare neurometabolic and neuromuscular diseases, D-2 and L-2 aciduria (DL-2HGA; OMIM: 615182) and congenital myasthenic syndrome-23 (CMS23; OMIM: 618197) [30][31][32] . There are no human cardiac phenotypes annotated to SLC25A1 defects (https://hpo.jax.org/app/browse/gene/6576), and it is unknown if SLC25A1 mutations underlie cardiac disease.…”

Exploring COVID-19 Vaccine Intentions, Perceptions, and Uptake Among the Saudi Population

“…Despite the implementation of various preventive measures and extensive efforts to vaccinate a significant portion of their populations, the reluctance or refusal to receive vaccination, even when readily available, remains a major global issue. Vaccine hesitancy is a recurring concern, especially with the introduction of new vaccines [ 21 ]. The rapid development of COVID-19 vaccines during the pandemic may further exacerbate this hesitancy [ 5 ].…”