Back
Children diagnosed with Alport syndrome (AS), an inherited kidney disorder, often display symptoms [1] such as hematuria, proteinuria, and progressive renal failure. Some patients with AS may also experience additional complications such as high-frequency sensorineural hearing loss, visual impairments, and other extrarenal symptoms. Nephrotic syndrom ein Alport's can be due to FSGS as part of the spectrumor due to podocyte depletion.
Malone et al. performed next-generation sequencing on 70 families with focal segmental glomerulosclerosis (FSGS) and discovered that 10% had variants in surprising ‘old’ genes, COL4A3 and COL4A4, which are involved in Alport syndrome and thin basement membrane nephropathy. These data show that a subset of renal manifestations associated with COL4A3 or COL4A4 variants cannot be distinguished from FSGS by clinical data or histopathology. Thus, a diagnosis of FSGS may sometimes fall within the spectrum of Alport syndrome.
23-year-old male patient known case of hearing impairment since the age of 14 years and new-onset proteinuria. His brother had a hearing impairment since the age of 9 years old and was incidentally found to have renal impairment in routine checkups resulting in end-stage renal disease. Given this family history, our patient got a genetic test which revealed that he was homozygous for the likely pathogenic variant in COL4A3 c.2939T>A p.Leu980 which caused autosomal recessive Alport syndrome.
His creatinine at that time was 84 micromol/L and eGFR 116 ml/min/1.73m2. On check-up, he was found to have significant proteinuria with a protein creatinine ratio of 11g/g. He had a kidney biopsy which confirmed his Alport syndrome and electron microscopy with moderate podocyte effacement and moderate chronic scarring.
A diagnosis of Alport syndrome with nephrotic range proteinuria due to podocytopathy was made ( images in result section). The patient was started on amlodipine 10 mg and telmisartan 80 mg combination, rosuvastatin 5 mg daily. His most recent protein creatinine ratio is 1.64 g/g.
Kidney biopsy of the patient with Alport syndrome images showed 2 views of electron microscopy with moderate podocyte effacement and Alport syndrome-associated membrane thickness and pattern.
Alport syndrome diagnosis usually is a clinical diagnosis confirmed by genetic studies. Kidney biopsy is not a usual diagnostic test for Alport syndrome, although in cases of nephrotic range proteinuria, it may explain the possible etiology of the proteinuria.