Management of the Most Common Functional Gastrointestinal Disorders in Infancy: The Middle East Expert Consensus

The occurrence of functional gastrointestinal disorders (FGIDs) is a formidable challenge for infants, parents, and healthcare professionals. Although data from the Middle East are scarce, experts consider FGIDs a prevalent condition in everyday clinical practice. The new Rome IV criteria revisited the definitions from a clinical perspective to provide a practical and consistent diagnostic protocol for FGIDs. However, the treatment practices for functional disorders vary considerably among Middle Eastern countries, often resulting in mismanagement with unnecessary investigations and treatments. In addition, the role of various treatment modalities, including probiotics such as Lactobacillus reuteri DSM 17938, in FGIDs requires further discussion and evaluation. During a consensus meeting, a locally relevant approach for treating common FGIDs such as infant regurgitation, infant colic, and functional constipation was discussed and approved by regional experts. The participants suggested a simplified treatment plan and protocol for general pediatricians and other primary care physicians managing FGIDs. This easy-to-follow standardized protocol will help streamline the initial management of this complex disorder in the Middle East region and even globally

<em>ADCK4</em> mutations promote steroid-resistant nephrotic syndrome through CoQ₁₀ biosynthesis disruption.

Identification of single-gene causes of steroid-resistant nephrotic syndrome (SRNS) has furthered the understanding of the pathogenesis of this disease. Here, using a combination of homozygosity mapping and whole human exome resequencing, we identified mutations in the aarF domain containing kinase 4 (ADCK4) gene in 15 individuals with SRNS from 8 unrelated families. ADCK4 was highly similar to ADCK3, which has been shown to participate in coenzyme Q(10) (CoQ(10)) biosynthesis. Mutations in ADCK4 resulted in reduced COQ(10). levels and reduced mitochondrial respiratory enzyme activity in cells isolated from individuals with SRNS and transformed lymphoblasts. Knockdown of adck4 in zebrafish and Drosophila recapitulated nephrotic syndrome-associated phenotypes. Furthermore, ADCK4 was expressed in glomerular podocytes and partially localized to podocyte mitochondria and foot processes in rat kidneys and cultured human podocytes. In human podocytes, ADCK4 interacted with members of the CoQ(10) biosynthesis pathway, including COQ6, which has been linked with SRNS and COQ7. Knockdown of ADCK4 in podocytes resulted in decreased migration, which was reversed by CoQ(10) addition. Interestingly, a patient with SRNS with a homozygous ADCK4 frameshift mutation had partial remission following CoQ(10) treatment. These data indicate that individuals with SRNS with mutations in ADCK4 or other genes that participate in CoQ(10) biosynthesis may be treatable with CoQ(10)