Cystinosis is caused by mutations in the CTNS gene (17p13.2), which encodes for a lysosomal cystine/proton symporter termed cystinosin. It is the most common cause of inherited renal Fanconi syndrome in young children. Because of its rarity, the diagnosis and specific treatment of cystinosis are frequently delayed, which has a significant impact on the overall prognosis. In this document, we have summarized expert opinions on several aspects of the disease to improve knowledge and provide guidance for diagnosis and treatment.

Purpose To investigate the utility of whole-exome sequencing (WES) to define a molecular diagnosis in patients clinically diagnosed with congenital anomalies of kidney and urinary tract (CAKUT). Methods WES was performed in 62 families with CAKUT. WES data were analyzed for Single Nucleotide Variants (SNVs) in 35 known CAKUT genes, putatively deleterious sequence changes in new candidate genes, and potentially disease-associated copy-number variants (CNVs). Results In approximately 5% of families, pathogenic SNVs were identified in PAX2, HNF1B, and EYA1. Observed phenotypes in these families expand the current understanding about the role of these genes in CAKUT. Four pathogenic CNVs were also identified using two CNV detection tools. In addition, we found one deleterious de novo SNV in FOXP1 among the 62 families with CAKUT. Database of clinical BMGL laboratory was queried and seven additional unrelated individuals with novel de novo SNVs in FOXP1 were identified. Six of these 8 individuals with FOXP1 SNVs, have syndromic urinary tract defects, implicating this gene in urinary tract development. Conclusion We conclude that WES can be used to identify the molecular etiology (SNVs, CNVs) in a subset of individuals with CAKUT. WES can also help identify novel CAKUT genes.

Carbamazepine intoxication is common in the pediatric population. Highly protein-bound, carbamazepine is not removed efficiently through conventional hemodialysis. We describe the use of albumin-enhanced continuous venovenous hemodialysis (CVVHD) in a 10-year-old girl who developed coma and respiratory depression due to an intentional carbamazepine overdose (peak drug level of 44.8 microg/ml; therapeutic range: 8-12 microg/ml). Without intervention, the half-life of drug elimination is 25 to 60 hours in patients who are naive to carbamazepine and 12 to 20 hours in children on chronic carbamazepine therapy. In contrast, with albumin-enhanced CVVHD, we observed a half-life of 7 to 8 hours. The patient recovered rapidly and was discharged from hospital <4 days from the time of ingestion with no complications or neurologic impairment. Because the cost-benefit analysis was also favorable relative to other therapeutic options, albumin-enhanced CVVHD may be the optimal treatment of toxic-level ingestion of carbamazepine.