Nephrological and urological complications of homozygous c.974G>A (p.Arg325Gln) OSGEP mutations

• Published in: Pediatric nephrology (Berlin, West) Vol. 33; no. 11; pp. 2201 - 2204
• Main Authors: Wang, Peter Zhan Tao, Prasad, Chitra, Rodriguez Cuellar, Carmen Inés, Filler, Guido
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.11.2018; Springer Nature B.V
• Subjects: Age; Brief Report; Calculi; Creatinine; Drug resistance; Epilepsy; Fanconi syndrome; Glomerular filtration rate; Hypercalciuria; Hypomagnesemia; Lithiasis; Magnesium; Medicine; Medicine & Public Health; Microencephaly; Mutation; Nephrology; Nephrotic syndrome; Pediatrics; Prophylaxis; Proteinuria; Seizures; Urinary tract; Urinary tract infections; Urine; Urology; Renal tubulopathy; Urolithiasis; tRNA N; Neurodegeneration; KAE1/TCS3 (OSGEP) mutation; adenosine threonylcarbamoyltransferase defect; Galloway-Mowat syndrome; tRNA N6-adenosine threonylcarbamoyltransferase defect
• ISSN: 0931-041X; 1432-198X
• DOI: 10.1007/s00467-018-4060-x

Background Galloway-Mowat syndrome (GAMOS) (OMIM #251300) is a severe autosomal recessive disease characterized by the combination of early-onset steroid-resistant nephrotic syndrome (SRNS) and microcephaly with brain anomalies caused by WDR73 as well as OSGEP , TP53RK , TPRKB , or LAGE3 mutations. Objective We report on the hitherto undescribed urological and nephrological complications of the homozygous c.974G>A (p.Arg325Gln) OSGEP mutations in a 7-year-old Caucasian girl. Case diagnosis The patient came to the attention of pediatric nephrology at the age of 3 years and 11 months, when she presented with status epilepticus due to profound hypomagnesemia (0.31 mmol/L, normal 0.65–1.05). A 24-h urine demonstrated a magnesium loss of 0.6 mmol/kg/day with associated proteinuria suggesting renal tubulopathy. Subsequently, she developed recurrent urinary tract infections (UTIs) and was diagnosed with neurogenic bladder dysfunction. The patient continued to have UTIs associated with seizures and sequential cultures growing multi-drug-resistant organisms despite of antibiotic prophylaxis. In addition, the proteinuria (median microalbumin/creatinine ratio 647 mg/mmol) increased, and she developed partial Fanconi syndrome. At age 7, she developed a large bladder calculus (3.3 × 3.2 cm) and three left non-obstructing renal calculi associated with elevated urinary cystine, hypercalciuria, and ongoing hypomagnesemia and required surgical intervention. Glomerular filtration rate (GFR) remained normal and she never developed frank nephrotic syndrome (average albumin 31 g/L). Conclusions It is unclear if patients with OSGEP mutations with tubular symptoms rather than nephrotic syndrome should be considered a different entity. Nephrological and urological complications of OSGEP mutations can be challenging and require a multidisciplinary approach.