Biallelic variants of the first Kunitz domain of SPINT2 cause a non-syndromic form of congenital diarrhea and tufting enteropathy.

Biallelic SPINT2 pathogenic variants cause a syndromic form of congenital diarrhea and enteropathy (OMIM 270420). To date, 35 patients have been reported and all presented with additional extra-intestinal features, apart from one case. We report on a 5-year-old girl who presented early in life with diarrhea and was found to have a novel homozygous variant in SPINT2. Pathological studies confirmed tufting enteropathy, and during her 5 years of life, she has not developed any extra-intestinal features. Molecular analysis detected a homozygous variant (NM_021102.4: c.203A>G (p. [Tyr68Cys]) in SPINT2. This is the first missense variant reported in the first Kunitz domain (KD1) of SPINT2 in humans. In vitro functional studies of this variant confirmed the deleterious effect leading to the loss of inhibitory activity of the intestinal serine proteases. This is the first description of SPINT2-related diarrhea in a patient who lived without long-term total parenteral nutrition. This study expands the clinical and molecular characteristics of SPINT2-related conditions.

Severe Neonatal Presentation of Progressive Familial Intrahepatic Cholestasis Type 4 in an Omani Infant.

Progressive familial intrahepatic cholestasis type 4 (PFIC4) is a relatively newly described autosomal recessive disorder caused by biallelic mutations in the gene encoding tight junction protein 2 (TJP2) which is located in chromosome 9q21. PFIC4 is characterised by cholestasis with or without other extrahepatic manifestations. Bleeding tendency due to vitamin k deficiency is a well-known complication of cholestasis. We present a neonate who presented to the Emergency Department at a tertiary care hospital in 2021 with cholestasis and multiple intracranial bleeds. He was found to have severe coagulopathy and his genetic work up revealed a homozygous variant mutation in TJP2 gene causing PFIC4. He had persistent cholestasis that necessitated an internal biliary diversion with some clinical improvement.

Domino liver transplantation for maple syrup urine disease in children: A single-center case series.

BACKGROUND: Domino liver transplant (DLT) represents another type of liver donor to expand the donor pool. Recent reports of successful DLT in children with maple syrup urine disease (MSUD) show promising long-term outcomes. METHODS: It was a retrospective study. All children with MSUD were paired with either recipients with end-stage liver disease (ESLD) or non-MSUD metabolic disease. Each pair underwent simultaneous liver transplant (LT), where the MSUD recipient received the graft from a living-related donor and the liver explanted from the MSUD donor was transplanted to the respective paired domino recipient. We report our experience regarding the techniques and outcomes of DLT at our center. RESULTS: Eleven children with MSUD and 12 respective DLT recipients were enrolled, one of which was domino split-liver transplantation. DLT recipients included seven ESLD, two propionic acidemia (PA), one glycogen storage disease(GSD) type-1, one GSD type-3, and one Citrullinemia. Post-LT ICU and hospital stays were comparable (p > .05). Patient and graft survival was 100% and 66.6% in the MSUD group and DLT recipients at a mean follow-up of 13.5 and 15 months. There was no death in the MSUD group as compared to four in the DLT group. The amino acid levels rapidly normalized after the LT in the children with MSUD and they tolerated the normal unrestricted diet. No vascular, biliary, or graft-related complications were seen in the post-transplant period. No occurrence of MSUD was noted in DLT recipients. CONCLUSION: DLTs have excellent post-surgical outcomes. DLT should be strongly considered and adopted by transplant programs worldwide to circumvent organ shortage.

Incidence and clinical characteristics of pediatric inflammatory bowel disease in Oman.

Background: Pediatric inflammatory bowel disease (PIBD) has been documented all over the world, and there is now a large body of clinical, pathological, and treatment knowledge and protocols in place in many countries. There is currently limited knowledge on the prevalence and pathology of PIBD in Omani population. The aim of this study is to report the incidence and clinical features of PIBD in Oman. Methods: This was a retrospective, cross-sectional, multicenter study carried out on all children <13 years of age between January 1, 2010 and December 31, 2021. Results: Fifty-one children were identified, 22 males (43.1%) and 29 females (56.9%), who were mostly from the Muscat region of Oman. The median incidence in the country was 0.57 (confidence interval [CI]: 0.31-0.64) per 105 children for inflammatory bowel disease (IBD), 0.18 (CI: 0.07-0.38) per 105 children for ulcerative colitis (UC), and 0.19 (CI: 0.12-0.33) per 105 children for Crohn's disease (CD). There was a significant increase in the incidence of all PIBD types after the year 2015. Bloody diarrhea was the most common symptom, followed by abdominal pain. Perianal disease affected nine children (40.9%) with CD. Conclusion: The incidence of PIBD in Oman is lower than in some neighboring Gulf countries but similar to that of Saudi Arabia. An alarming upward trend was noted from the year 2015. Large-scale population-based studies are required to investigate the possible causes of this increasing incidence.

Intramural duodenal haematoma in a child post-endoscopic biopsy.

Intramural duodenal haematoma is a rare complication of endoscopic biopsy. Though other causes such as blunt abdominal trauma are more common, it remains a rare problem in paediatric population. In this article, we report a patient who developed intramural duodenal haematoma following an endoscopic biopsy that was performed to look for evidence of gut graft versus host disease.

Cystic biliary atresia in a neonate with antenatally detected abdominal cyst.

Cystic biliary atresia (BA) is a rare but an important type of BA. An antenatally detected cystic lesion at the porta hepatis raises the suspicion of cystic BA. It is very important to differentiate this from choledochal cyst in infants with cholestasis and cystic lesions. This case report outlines the clinical presentation and radiological findings of an infant who had an antenatally detected intra-abdominal cystic mass, thought to be a choledochal cyst.

Hereditary Angioedema Post-liver Transplant.

Liver transplantation is the standard of care in managing different types of liver disorders as well as a variety of inborn errors of metabolism. In the latter scenario, the liver-based enzyme abnormality is corrected by transplantation. Although rare, liver transplantation may result in the transmission of an inborn error of metabolism to the recipient. The present report describes the development of acquired hereditary angioedema likely following liver transplantation, with notable improvement with the initiation of C1 esterase inhibitor replacement therapy. This case report describes another example of a hepatic synthesis defect that, although rare, but can be acquired from donor's livers.