Autism spectrum disorder (ASD) is a heritable neurodevelopmental disorder with the underlying etiology yet incompletely understood and no cure treatment. Patients of fragile X syndrome (FXS) also manifest symptoms, e.g. deficits in social behaviors, that are core traits with ASD. Several studies demonstrated that a mutual defect in retinoic acid (RA) signaling was observed in FXS and ASD. However, it is still unknown whether RA replenishment could pose a positive effect on autistic-like behaviors in FXS. Herein, we found that RA signaling was indeed down-regulated when the expression of FMR1 was impaired in SH-SY5Y cells. Furthermore, RA supplementation rescued the atypical social novelty behavior, but failed to alleviate the defects in sociability behavior or hyperactivity, in Fmr1 knock-out (KO) mouse model. The repetitive behavior and motor coordination appeared to be normal. The RNA sequencing results of the prefrontal cortex in Fmr1 KO mice indicated that deregulated expression of Foxp2, Tnfsf10, Lepr and other neuronal genes was restored to normal after RA treatment. Gene ontology terms of metabolic processes, extracellular matrix organization and behavioral pathways were enriched. Our findings provided a potential therapeutic intervention for social novelty defects in FXS.
1. Case presentation A 4‐month‐old female infant was admitted to our clinical ward in May 2021 due to her skin manifestation of the jaundice since birth. Her symptoms aggravated progressively despite various medications (e.g. Ursodeoxycholic Acid, Stronger Neo‐Minophagen C Tablets) were prescribed. Initial Work‐up. The admission abdominal ultrasound demonstrated contracted gallbladder, with no sign of common bile duct. Two weeks ago, she was admitted into Pediatric ICU, where her conditions worsened to coagulation dysfunction, digestive tract hemorrhage and hypotension. Diagnosis and Management. With initial work‐ups, the patient was diagnosed with congenital biliary atresia, liver cirrhosis, respiratory failure secondary to severe pneumonia (aspergillus and mycoplasma infections), secundum atrial septal defect (ASDII, 9.7mm) and hypoalbuminemia. Accordingly, CPAP‐assisted ventilation, injections of meropenem, vancomycin, and carprofen, as well as IVIG (2g/kg) and vitamin K1 were admitted. Echocardiogram confirmed pulmonary artery hypertension (PAH), right atrial enlargement, and portal hypertension. Further, she exhibited right heart failure (HF) symptoms, such as abdominal effusion, lower extremity edema. An urgent percutaneous ASD closure was scheduled prior to the parent‐to‐offspring liver transplantation, thereby reducing the high risk of right HF and PAH during the surgery. 2. Surgical procedures Briefly, a venous access was probed in groin area under local anesthesia (1% lidocaine). Upon bleeding, a 6F venous sheath tube (FAST‐CATHTM, ST.JUDE Medical) was gently inserted into the right femoral vein, followed by a Cordis MPA catheter (Cordis 6F, Johnson & Johnson Inc), which was further threaded through the vessel into heart. Once MPA catheter reached the left superior pulmonary vein through ASD, we released the guidewire and retracted the venous sheath tube simultaneously. (Fig. 1) Next, we inserted a 9F delivery sheath tube to transport the 10mm MemoPart™ ASD Occluder (FQFDQ‐I 10, SHSMA Corp) into anatomical left atrium through the interatrial hole. Once the umbrella at both atrial sides was released consecutively forming a sandwich‐like skeleton, the closure was successfully completed along with retraction of the occluder. (Fig.2) 3. Follow‐up One week after ASD closure, she received a living‐donor liver transplantation, and her liver function returned to normal shortly, with no further cirrhosis‐associated complications. Before discharge, echocardiogram demonstrated no shunt exist. (Fig.3) 4. Discussion Statistically, 15.8% of liver‐transplant recipients are having cardiovascular diseases, among whom 30% are diagnosed with ASD. Most children with ASD remain asymptomatic and their physical activities are typically unaffected till adolescence. Congestive HF and PAH will occur in patients with medium‐to‐large ASD around the age of 20‐30 years. In our case, the child was very young, yet with an extremely complicated condition requiring multiple resuscitation procedures. The large left‐to‐right shunt volume ...
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