Renal tract abnormalities missed in a historical cohort of young children with UTI if the NICE and AAP imaging guidelines were applied.

OBJECTIVE: In a historical cohort of children with a urinary tract infection (UTI) who had already undergone all the imaging procedures, the aim was to determine renal tract abnormalities which would have been missed had we implemented the new guidelines from the National Institute for Health and Care Excellence in the United Kingdom (NICE) or the American Academy of Pediatrics (AAP). MATERIAL AND METHODS: After a UTI episode, forty-three children (28 females, 65%) aged between 2 months and 2 years presenting at two general hospitals with a febrile UTI before 2008 underwent all the recommended imaging studies predating the new guidelines. Hydronephrosis was defined and graded according to the Society for Fetal Urology (SFU) classification. Hydronephrosis grade II (mild pelvicalyceal dilatation), grade III (moderate dilatation), and grade IV (gross dilatation with thinning of the renal cortex), duplication, vesicoureteral reflux (VUR) grade II and above, renal scarring and reduced renal uptake (<45%) on technetium-99m-labeled dimercaptosuccinic acid (DMSA) scintigraphy were considered significant abnormalities. We calculated the proportion of abnormalities which would have been missed had the new guidelines been used instead. RESULTS: The median of age was 7.6 months (mean 8.7, range 2-24 months), with the majority (n = 37, 86%) being under 1 year of age. Ultrasound (US) showed hydronephrosis in 14 (32%), all grade II. A voiding cystourethrogram (VCUG) was performed in all and showed VUR ≥ grade II in 16 (37%), including eight children (19%) where it was bilateral. DMSA scan showed scarring in 25 children (58%) of whom 11 (26%) had bilateral scars. Reduced differential renal uptake was present in 10 children (23%). Of the 29 children with normal US, 18 (62%) had renal scarring and nine (31%) had VUR ≥ grade II. The NICE guidelines would have missed 63% of the children with VUR ≥ grade II, including a high proportion of grades IV and V VUR, 44% of the children with renal scarring, and 20% of the children with decreased renal uptake, including some children with bilateral renal scarring and with decreased renal uptake. The AAP guidelines would have missed 56% of the children with VUR ≥ grade II, including a high proportion of grades IV and V VUR, and all children with renal scarring as well as those with decreased renal uptake. CONCLUSION: The prevalence of renal tract abnormalities missed by the new guidelines is high. They should be used with full awareness of their limitations.

Clinical and molecular analysis of isovaleric acidemia patients in the United Arab Emirates reveals remarkable phenotypes and four novel mutations in the IVD gene.

Isovaleric acidemia (IVA) is an autosomal recessive inborn error of leucine metabolism caused by deficiency of mitochondrial isovaleryl-CoA dehydrogenase (IVD). Accumulation of isovaleryl-CoA derivatives to toxic levels results in clinical symptoms of the disease. Here, we investigate the clinical and molecular features of Arab patients with IVA. Patients from five unrelated families were evaluated clinically and for defects in the IVD gene. Four novel mutations (p.F382fs, p.R392H, p.R395Q and p.E408K) have been identified with p.R395Q occurring in two families. In addition, molecular modeling of the identified missense mutations predicted their damaging effects on the protein and computational analysis of the p.F382fs mutation predicted the disruption of a 3' splicing site resulting in inactive or unstable gene product. Furthermore, we found an unusual case of a 17 years old female homozygous for the p.R392H mutation with no clinical symptoms. Our results illustrate a heterogeneous mutation spectrum and clinical presentation in the relatively small UAE population.