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Author(s): William D. Wood [sup.1] , Ayah Elmaghrabi [sup.1] , Garrett Gotway [sup.2] , Matthias T. F. Wolf [sup.1] Author Affiliations: (1) grid.267313.2, 0000 0000 9482 7121, Pediatric Nephrology, University [...], Background Cobalamin C (cblC), a vitamin B12 processing protein, plays a crucial role in metabolism for the conversion of homocysteine to methionine and methylmalonyl-CoA to succinyl-CoA. CblC deficiency, an inborn error of cobalamin processing, is a rare cause of atypical hemolytic-uremic syndrome (aHUS) and results in hyperhomocysteinemia and methylmalonic aciduria. Both substances are thought to contribute to thrombotic microangiopathy (TMA) in cblC deficiency patients. However, the roles of homocysteine and methylmalonic acid (MMA) in these patients remain unclear. We want to shed more light on the contributions of homocysteine and MMA levels as contributing factors for thrombotic microangiopathy (TMA)/aHUS by a follow-up of a cblC deficiency patient over 6 years. Case diagnosis A 27-day-old Hispanic female presented with abnormal C3-carnitine on her newborn screen, poor feeding, decreased activity, and oligouria. She was diagnosed with cblC deficiency after laboratory results revealed elevated serum homocysteine, and serum MMA along with genetic testing showing a homozygous pathogenic frameshift variant in MMACHC. The patient developed aHUS and acute kidney injury (AKI), which resolved after appropriate therapy. Over 6 years, she continued to have normal kidney function with no thrombocytopenia despite persistently elevated homocysteine and MMA levels. Conclusion We question the roles of homocysteine and MMA as causative of aHUS/TMA in cblC deficiency as they remained elevated during follow-up but did not result in aHUS/TMA or AKI. Hyperhomocysteinemia and/or MMA caused by other metabolic diseases do not result in aHUS/TMA or AKI. This suggests that other nephrotoxic factors may trigger aHUS/TMA in cblC patients.

Author(s): Anthony J. Bleyer [sup.1] [sup.2] , Matthias T. Wolf [sup.3] , Kendrah O. Kidd [sup.1] [sup.2] , Martina Zivna [sup.2] , Stanislav Kmoch [sup.1] [sup.2] Author Affiliations: (1) grid.241167.7, [...], Autosomal dominant tubulointerstitial kidney disease (ADTKD) refers to a group of disorders with a bland urinary sediment, slowly progressive chronic kidney disease (CKD), and autosomal dominant inheritance. Due to advances in genetic diagnosis, ADTKD is becoming increasingly recognized as a cause of CKD in both children and adults. ADTKD-REN presents in childhood with mild hypotension, CKD, hyperkalemia, acidosis, and anemia. ADTKD-UMOD is associated with gout and CKD that may present in adolescence and slowly progresses to kidney failure. HNF1[beta] mutations often present in childhood with anatomic abnormalities such as multicystic or dysplastic kidneys, as well as CKD and a number of other extra-kidney manifestations. ADTKD-MUC1 is less common in childhood, and progressive CKD is its sole clinical manifestation, usually beginning in the late teenage years. This review describes the pathophysiology, genetics, clinical characteristics, diagnosis, and treatment of the different forms of ADTKD, with an emphasis on diagnosis. We also present data on kidney function in children with ADTKD from the Wake Forest Rare Inherited Kidney Disease Registry.

Author(s): Ahmad Mashmoushi [sup.1] , Abha Choudhary [sup.2] , Christie P. Thomas [sup.3] , Matthias T. F. Wolf [sup.1] [sup.4] Author Affiliations: (1) grid.267313.2, 0000 0000 9482 7121, Pediatric Nephrology, [...]

Author(s): Ahmad Mashmoushi [sup.1] , Abha Choudhary [sup.2] , Christie P. Thomas [sup.3] , Matthias T. F. Wolf [sup.1] [sup.4] Author Affiliations: (1) grid.267313.2, 0000 0000 9482 7121, Pediatric Nephrology, [...]