A Rare Case of Autosomal Recessive Alport Syndrome Due to Mutation in COL 4A4 Gene with 1 Base Pair Duplication of Cytosine Nucleotide —A Rare Mutation in Alport Syndrome

Abstract

Background : Alport syndrome (AS) is a rare genetic disorder due to mutations in type IV collagen genes. The case : A 16-year-old boy was referred for management of moderate renal disease and hypertension that was disclosed after routine testing for sensorineural deafness. Laboratory tests showed serum creatinine at 200 umol/L, microscopic hematuria and proteinuria at 2.6 g/day. Diagnosis of Alport syndrome (AS) was established by kidney biopsy and genetic testing that disclosed a rare AS-mutation. The biopsy showed focal and segmental glomerulosclerosis, without deposits on immunofluorescent stains, and abnormal glomerular basement membrane with a basket-weave appearance on electron microscopy. Genetic testing showed homozygous frameshift insertion in COL4A4 gene that consisted of 1 base pair duplication of cytosine nucleotide resulting in splice-site changes. Genetic testing of both parents did not show abnormality, indicating a new mutation in this patient. He was treated with Ramipril 5 mg daily and diet low in salt and protein. By 1 year later; he remained stable with serum creatinine at 219 umol/L, albumin at 39 g/L and protein excretion at 450 mg/day. Conclusion : AS can evolve due to new cytosine mutations in aggressive renal disease that can be ameliorated with angiotensin-converting enzyme inhibitors.