Triple Threat! A Case of Lowe Syndrome with Triple Genetic Mutations

Introduction: Lowe syndrome (LS), also known as Oculocerebrorenal Syndrome of Lowe (OCRL), is an extremely rare multisystem disorder that primarily affects the eyes, brain, and kidneys. It is inherited in an X-linked manner and is caused by a deficiency of inositol biphosphate 5-phosphatase, localized to the Golgi complex. Here, we report a case with a unique combination of genetic variations in the OCRL, Collagen-4 A3 (COL4A3), and Apolipoprotein-1 (APOL1) genes. Case Description: A 33-year-old male with a history of congenital cataracts, cerebral palsy, significant growth retardation, and proximal kidney tubular dysfunction, including proteinuria was diagnosed with Lowe syndrome between the ages of 7 and 9. During a routine follow-up his urine protein-to-creatinine ratio increased to 2.23 g/g, and his chronic kidney disease (CKD) progressed, as evidenced by a decrease in Cystatin C estimated glomerular filtration rate from 52 ml/min/1.73m2 to 46 ml/min/1.73m2. Genetic testing confirmed the presence of a genetic mutation in the OCRL gene, a heterozygous mutation in COL4A3 gene and a high risk APOL1 allele. In light of these findings, a kidney biopsy was performed, revealing extensive global glomerulosclerosis and segmental thinning of the glomerular basement membrane (GBM) up to 168 nm and lamellated thickening of the tubular basement membranes. He continued to follow up in the nephrology clinic with plan to optimize anti-proteinuric therapy. Discussion: Lowe Syndrome occurs almost exclusively in males due to mutations in the OCRL gene and has an estimated prevalence of approximately 1 in every 500,000 children. Although not pathognomonic, lamellated tubular basement membranes have been reported in patients with OCRL gene abnormalities which may explain proximal tubular dysfunction. The presence of segmental thinning in the GBM could raise the possibility of early changes secondary to his COL4A3 mutation. To our knowledge, this is the first report of a patient with Lowe syndrome presenting with triple genetic variations. The biopsy enhanced our understanding of the etiology of CKD in this patient.