Normal IQ is possible in Smith-Lemli-Opitz syndrome.

Children with Smith-Lemli-Opitz syndrome (SLOS) are typically reported to have moderate to severe intellectual disability. This study aims to determine whether normal cognitive function is possible in this population and to describe clinical, biochemical and molecular characteristics of children with SLOS and normal intelligent quotient (IQ). The study included children with SLOS who underwent cognitive testing in four centers. All children with at least one IQ composite score above 80 were included in the study. Six girls, three boys with SLOS were found to have normal or low-normal IQ in a cohort of 145 children with SLOS. Major/multiple organ anomalies and low serum cholesterol levels were uncommon. No correlation with IQ and genotype was evident and no specific developmental profile were observed. Thus, normal or low-normal cognitive function is possible in SLOS. Further studies are needed to elucidate factors contributing to normal or low-normal cognitive function in children with SLOS.

T cell co-stimulatory molecules: a co-conspirator in the pathogenesis of eosinophilic esophagitis?

Eosinophilic esophagitis (EoE) has become a common gastrointestinal disease. It is characterized by severe eosinophil infiltration in the esophagus. EoE is strongly associated with food allergy, asthma, atopic dermatitis, and other allergic diseases. T lymphocytes, especially Th2 cells, play an instrumental role in the development of allergic inflammation. Recent studies have shown that the ligation of co-stimulatory molecules contributes to the activation, differentiation, and proliferation of T cells. In this review, we will discuss the growing evidence of co-stimulatory molecules including OX40, Light, and HVEM in the pathogenesis of Th2-driven EoE. Our goal is to provide the rationale for the development of novel therapy therapies that target co-stimulatory molecules.

Treatment of Smith-Lemli-Opitz syndrome and other sterol disorders.

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive genetic condition with a broad phenotype that results from deficiency of the final enzyme of the cholesterol synthesis pathway. This defect causes low or low-normal plasma cholesterol levels and increased 7- and 8-dehydrocholesterol (DHC) levels. Many therapies for SLOS and other disorders of sterol metabolism have been proposed, and a few of them have been undertaken in selected patients, but robust prospective clinical trials with validated outcome measures are lacking. We review the current literature and expert opinion on treatments for SLOS and other selected sterol disorders, including dietary cholesterol therapy, statin treatment, bile acid supplementation, medical therapies, and surgical interventions, as well as directions for future therapies and treatment research.

Smith-Lemli-Opitz syndrome.

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive, multiple congenital malformation and intellectual disability syndrome, with clinical characteristics that encompass a wide spectrum and great variability. Elucidation of the biochemical and genetic basis for SLOS, specifically understanding SLOS as a cholesterol deficiency syndrome caused by mutation in DHCR7, opened up enormous possibilities for therapeutic intervention. When cholesterol was discovered to be the activator of sonic hedgehog, cholesterol deficiency with inactivation of this developmental patterning gene was thought to be the cause of SLOS malformations, yet this explanation is overly simplistic. Despite these important research breakthroughs, there is no proven treatment for SLOS. Better animal models are needed to allow potential treatment testing and the study of disease pathophysiology, which is incompletely understood. Creation of human cellular models, especially models of brain cells, would be useful, and in vivo human studies are also essential. Biomarker development will be crucial in facilitating clinical trials in this rare condition, because the clinical phenotype can change over many years. Additional research in these and other areas is critical if we are to make headway towards ameliorating the effects of this devastating condition.

Cholbam® and Zellweger spectrum disorders: treatment implementation and management.

BACKGROUND: Zellweger spectrum disorders (ZSDs) are a rare, heterogenous group of autosomal recessively inherited disorders characterized by reduced peroxisomes numbers, impaired peroxisomal formation, and/or defective peroxisomal functioning. In the absence of functional peroxisomes, bile acid synthesis is disrupted, and multisystem disease ensues with abnormalities in the brain, liver, kidneys, muscle, eyes, ears, and nervous system. MAIN BODY: Liver disease may play an important role in morbidity and mortality, with hepatic fibrosis that can develop as early as the postnatal period and often progressing to cirrhosis within the first year of life. Because hepatic dysfunction can have numerous secondary effects on other organ systems, thereby impacting the overall disease severity, the treatment of liver disease in patients with ZSD is an important focus of disease management. Cholbam® (cholic acid), approved by the U.S. Food and Drug Administration in March 2015, is currently the only therapy approved as adjunctive treatment for patients with ZSDs and single enzyme bile acid synthesis disorders. This review will focus on the use of CA therapy in the treatment of liver disease associated with ZSDs, including recommendations for initiating and maintaining CA therapy and the limitations of available clinical data supporting its use in this patient population. CONCLUSIONS: Cholbam is a safe and well-tolerated treatment for patients with ZSDs that has been shown to improve liver chemistries and reduce toxic bile acid intermediates in the majority of patients with ZSD. Due to the systemic impacts of hepatic damage, Cholbam should be initiated in patients without signs of advanced liver disease.

Pediatric eosinophilic esophagitis: single-center experience in northwestern USA.

BACKGROUND: Eosinophilic esophagitis (EE) is an emerging disease. Its incidence and prevalence have been exponentially increasing in the last decade. The clinical manifestations of EE vary especially in children. Allergic reaction is strongly implicated in the disease. The aim of the present study was to retrospectively examine the demographic, clinical, laboratory, and endoscopic features of pediatric patients with EE, in order to better understand the diversity of the disease, thereby improving clinical diagnosis and treatment. METHODS: The data were retrospectively collected from 20 pediatric patients with biopsy-proven EE. Demographic information, clinical symptoms and duration, as well as endoscopic findings were correlated and statistically analyzed. RESULTS: Median age at diagnosis was 11 years. Male patients had higher prevalence of EE. Thirty-five percent of the children had food allergy on either skin prick test or IgE radioallergosorbent test, and atopic diseases were common in the group. Gastroesophageal reflux appeared to be the major symptom in younger children, whereas dysphagia and food impaction were more common in older patients. The referral and final diagnosis were often delayed. Esophageal white exudates were the most prominent feature in the younger age group, whereas esophageal ring-like lesion occurred more often in older children. CONCLUSION: EE is more common in male subjects. The clinical and endoscopic features depend upon the age. Allergic processes are strongly involved in pathogenesis. The present results will improve understanding of the characteristics of the disease in the pediatric population and enhance clinicians' vigilance for the diagnosis of EE.

Hepatic encephalopathy.

Hepatic encephalopathy is characterized by a wide spectrum of neuropsychiatric abnormalities and motor disturbances in patients with advanced liver disease. It is estimated to occur in 30% to 45% of patients with liver cirrhosis and in 10% to 50% of patients with transjugular intrahepatic portosystemic shunts. It can be seen in cancer patients due to multiple factors. Early diagnosis and treatment are important but can be challenging, especially in mild forms with subtle findings. This article reviews the pathogenesis, diagnostic criteria, grading, and management of hepatic encephalopathy.