Mutations in tetratricopeptide repeat domain 7A result in a severe form of very early onset inflammatory bowel disease.

BACKGROUND & AIMS: Very early onset inflammatory bowel diseases (VEOIBD), including infant disorders, are a diverse group of diseases found in children younger than 6 years of age. They have been associated with several gene variants. Our aim was to identify the genes that cause VEOIBD. METHODS: We performed whole exome sequencing of DNA from 1 infant with severe enterocolitis and her parents. Candidate gene mutations were validated in 40 pediatric patients and functional studies were carried out using intestinal samples and human intestinal cell lines. RESULTS: We identified compound heterozygote mutations in the Tetratricopeptide repeat domain 7 (TTC7A) gene in an infant from non-consanguineous parents with severe exfoliative apoptotic enterocolitis; we also detected TTC7A mutations in 2 unrelated families, each with 2 affected siblings. TTC7A interacts with EFR3 homolog B to regulate phosphatidylinositol 4-kinase at the plasma membrane. Functional studies demonstrated that TTC7A is expressed in human enterocytes. The mutations we identified in TTC7A result in either mislocalization or reduced expression of TTC7A. Phosphatidylinositol 4-kinase was found to co-immunoprecipitate with TTC7A; the identified TTC7A mutations reduced this binding. Knockdown of TTC7A in human intestinal-like cell lines reduced their adhesion, increased apoptosis, and decreased production of phosphatidylinositol 4-phosphate. CONCLUSIONS: In a genetic analysis, we identified loss of function mutations in TTC7A in 5 infants with VEOIBD. Functional studies demonstrated that the mutations cause defects in enterocytes and T cells that lead to severe apoptotic enterocolitis. Defects in the phosphatidylinositol 4-kinase-TTC7A-EFR3 homolog B pathway are involved in the pathogenesis of VEOIBD.

A Male Infant with Abetalipoproteinemia: A Case Report from Iran.

Abetalipoproteinemia (ABL) is a very rare autosomal recessive disorder caused by mutations in the microsomal triglyceride transfer protein gene (MTTP). ABL is characterized by lack of lipids and apolipoprotein B (apoB) in plasma, fat malabsorption and various clinical manifestations. We describe a 12-month-old infant boy, born from consanguineous parents and presented with diarrhea, steatorrhea, growth retardation, hypothyroidism, intraventricular brain cyst and kidney stones. The patient was diagnosed to have ABL and treated with dietary modification and oral fat-soluble vitamin replacement and followed until he reached 5 years of age.

Unexplained neonatal jaundice as an early diagnostic sign of urinary tract infection.

BACKGROUND: Hyperbilirubinemia is one of the presenting signs of bacterial infection in newborns, and the association of neonatal jaundice with urinary tract infection (UTI) has been particularly emphasized. The aim of this study was to determine the prevalence of UTI in asymptomatic jaundiced neonates younger than 4 weeks old. METHODS: We prospectively evaluated 120 asymptomatic jaundiced and 122 healthy neonates without jaundice younger than 4 weeks old for UTI. Patients with UTI, defined as >10,000 colony-forming units of a single pathogen per milliliter urine obtained by bladder catheterization, were evaluated for sepsis. RESULTS: Of 120 asymptomatic jaundiced neonates with a mean age of 7 ± 4 days, 15 (12.5%) had a UTI. Of 122 healthy neonates, positive urine cultures from a urine bag were found in eight cases; however on reevaluation, urine cultures from bladder catheterization were negative. The most common pathogen isolated from the UTI cases was Klebsiella pneumoniae. Also, unconjugated hyperbilirubinemia was detected in all jaundiced patients with UTI. CONCLUSION: UTI was found in 12.5% of the asymptomatic jaundiced neonates with the onset of unconjugated hyperbilirubinemia in the first week of life. Therefore, we suggest that urine culture should be considered as a part of the diagnostic evaluation of jaundiced neonates older than 3 days with an unexplained etiology.