A new mutation in the C-terminal end of TTC37 leading to a mild form of syndromic diarrhea/tricho-hepato-enteric syndrome in seven patients from two families.

Syndromic diarrhea/tricho-hepato-enteric syndrome (SD/THE) is a rare congenital enteropathy with seven main clinical features: intractable diarrhea of infancy, hair abnormalities, intrauterine growth restriction (IUGR), facial dysmorphism, immune dysfunction, and liver and skin abnormalities. SD/THE is caused by mutations in TTC37 or SKIV2L, two genes encoding components of the human SKI complex. To date, approximately 50 SD/THE patients have been described with a wide spectrum of mutations, and only one recurrent mutation has been identified in independent families. We present a detailed description of seven patients of Turkish origin with the same new mutation in TTC37: c.4572 G>A p.(Trp1524X). All seven patients were homozygous for this mutation and presented the typical clinical features of SD/THE, but with a milder presentation than usual. All seven patients were alive at the last follow-up. Four out of seven patients had no IUGR, and four patients never required parenteral nutrition. All patients presented a better growth rate than previously described in patients with SD/THE, with 4/7 above the 3rd percentile. The mutation is localized only forty amino acids from the end of TTC37, and as TTC37 is longer than the yeast SKI3, it is possible that a truncated protein is expressed and plays a reduced role in the SKI complex.

Surgery and postoperative recurrence in children with Crohn disease.

OBJECTIVES: The aim of this study was to describe surgery rates, complications, and risk of disease recurrence after surgery in paediatric Crohn disease (CD). METHODS: Children <18 years with a diagnosis of CD and a least 1 intestinal resection from the period January 1, 1978 to December 31, 2007 were identified using the Danish National Patient Registry. Patient charts were used to extract data. RESULTS: A total of 115 of 422 children with CD, who had surgery in 2 referral centres, were further studied. Disease extension according to the Montreal classification at the time of operation was available in 106/115 patients: B1, 39/106 (37%); B2, 59/106 (56%); and B3, 8/106 (7%). Before/after surgery 89%/36% of the patients received corticosteroids, 26%/61% azathioprine, and 15%/34% infliximab. Ileocoecal resection was performed in 54 (47%); 17 (15%) underwent ileal resection, 21 (18%) colectomy, 13 (11%) hemicolectomy, and 10 (9%) a combined colonic and ileal resection. Median time from diagnosis to surgery was 23 months (range 0-147). The median follow-up time after surgery was 121 months (16-226), and median time to disease recurrence was 12 months (3-160). The cumulative clinical recurrence rates at 1, 5, and 10 years were 50%, 73%, and 77%, respectively. More than 1 bowel resection was needed in 39%. Postoperative azathioprine treatment did not affect rate of recurrence after surgery. CONCLUSIONS: In this large cohort of children with CD studied for >10 years postoperatively, we found a high postoperative recurrence rate of disease and a frequent need for >1 intestinal resection.

Does infliximab prevent colectomy in acute and chronic active ulcerative colitis?

OBJECTIVES: The aim of the study was to evaluate clinical response, use of colectomy, and adverse events related to infliximab (IFX) treatment in acute and chronic active ulcerative colitis (UC) in children. METHODS: Children from 3 centers, who had received IFX for UC, were identified, and patient charts were reviewed retrospectively. Data concerning symptoms, biochemistry, concomitant medical treatment, colectomy, and adverse events were registered. RESULTS: A total of 45 patients with UC (median age at diagnosis 12 years, interquartile range 10-14) were included, and studied for a median of 15 months (interquartile range 4.5-29) after first IFX infusion. The cumulative 1- and 2-year risks of colectomy were 21% and 26%, respectively. The cumulative 1- and 2-year risks of receiving a new course of systemic corticosteroids were 32% and 48%, respectively. Twenty-one patients (46%) experienced adverse events. Most common were mild infusion reactions, but 3 (7%) had serious adverse events. CONCLUSIONS: IFX was efficient in preventing colectomy in children with UC. The risk of receiving systemic corticosteroids was lower than that reported in other studies. Most adverse events were mild to moderate and self-limiting.