In Gaucher disease, defective lysosomal glucocerebrosidase due to mutations in the GBA1 gene results in lysosomal accumulation of glucocerebroside in mononuclear phagocytes and a multisystemic phenotype. Observations of occurrence of Parkinson's disease in some patients with non-neuronopathic type 1 Gaucher disease (GD1) and their first degree relatives has led to the identification of GBA1 heterozygous mutations as a genetic risk factor for idiopathic Parkinson's disease (PD). However, the magnitude of risk of PD in patients with known GD1 has not been determined, and it is not known whether GD1/PD represents a specific sub-phenotype of GD1 with distinctive genotype/phenotype characteristics. We estimated the risk of PD in a cohort of 444 consecutively evaluated patients with GD1 compared to that in the general population. Eleven patients developed parkinsonian syndrome during a 12-year follow-up period. The adjusted life-time NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript risk ratio of PD in GD1 compared to that in the general population was 21.4 [95% confidence interval (95% CI) 10.7-38.3], with a higher risk in men compared to women. In our cohort, GD1/Parkinson's disease phenotype (GD1/PD) was characterized by higher GD1 severity score, due to higher incidence of avascular osteonecrosis. The clinical spectrum of PD varied from mild to potentially life-threatening disease. All but one patient with GD1/PD phenotype had at least one N370S GBA1 allele. In conclusion, compared to the general population, patients with GD1 have an almost 20-fold increased life-time risk of developing PD.

Objectives-Acute pancreatitis is a necroinflammatory disease that leads to 210,000 hospitalizations in the United States annually. Recent reports suggest that there may be important differences in clinical features between infants/toddlers and older children. Thus, in this study we make a direct comparison between the pediatric age groups in presentation and management trends of acute pancreatitis. Patients and Methods-We examined all children (ages 0 to 20 years) admitted to Yale-New Haven Children's Hospital with pancreatitis between 1994 and 2007.Results-Two hundred seventy-one cases met inclusion criteria for acute pancreatitis. Infants and toddlers manifested fewer signs and symptoms of abdominal pain, epigastric tenderness, and nausea compared with older children (43% vs 93%; 57% vs 90%; and 29% vs 76%, respectively; P < 0.05 for all comparisons). They were more likely to be diagnosed by serum lipase than by amylase and to undergo radiographic evaluation (P < 0.05). They had a longer hospital stay (19.5 vs 4 days; P < 0.05) and were less likely to be directly transitioned to oral nutrition (14% vs 71%; P < 0.05).Conclusions-Infants and toddlers with acute pancreatitis present with fewer classical symptoms and are managed differently from older children. We believe these data will be helpful in evaluating and understanding treatment practices in this age group. Keywords acute pancreatitis; amylase; infants; lipase; toddlers Acute pancreatitis is a necroinflammatory disease of the pancreas that has many associated etiologies such as common bile duct stones, alcohol, trauma, medications, toxins, and ductal defects. Acute pancreatitis accounts for more than 210,000 annual hospital admissions (1) and, tallied with chronic pancreatitis, leads to 31,000 deaths per year (2). Although practice parameters for acute pancreatitis are currently evolving using primarily adult studies, information about children is lacking. Although in children there are several studies examining pancreatitis incidence and etiology (3-7), few have characterized their clinical presentation and management (8,9). We hypothesized that in our pediatric population of NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript acute pancreatitis in New Haven, Connecticut, there are also age-related differences in the management of acute pancreatitis. Indeed, we found that infants and toddlers differ from older children in clinical presentation, level of serum biomarker elevation, type of radiographic evaluation, length of hospitalization, and mode of nutrition. PATIENTS AND METHODS Study GroupA retrospective chart review was conducted at Yale-New Haven Children's Hospital, New Haven. Children (younger than 21 years) admitted between August 1994 and July 2007 were screened for International Classification of Diseases-9 codes pertaining to pancreatitis. The study was approved by the Yale University School of Medicine institutional review board. Details of the cohort, including referral trends for pancreatitis over time, eti...

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Crohn’s disease is an immune-related disorder characterized by inflammation of the gastrointestinal mucosa, which can occur in any area throughout the digestive tract. This life-long disease commonly presents with abdominal pain, diarrhea, vomiting, and weight loss. While the exact etiology of this disease is largely unknown, it is thought to arise from an interaction between microbial, immunological, and environmental factors in a genetically susceptible host, whereby the immune system attacks the intestine as it cross reacts against gut microbial antigens. The study of genetic variants associated with Crohn’s disease has shed light on our understanding of disease pathophysiology. A large number of genetic variants identified in Crohn’s disease are related to genes targeting microbial recognition and bacterial wall sensing, the most common being NOD2/CARD15 gene. This review will discuss the recent advance in our knowledge of genetic variants of this disease and how they influence the disease course and prognosis.