A rare dual diagnosis of Alport syndrome and Charcot-Marie-Tooth disease

Alport syndrome is one of the rare genetic disorders affecting approximately 1 in 50,000 individuals. Main features: Progressive microscopic hematuria, proteinuria, which progresses to chronic kidney disease (CKD), associated with sensorineural hearing loss and ocular abnormalities. The Alport syndrome results from mutations in collagen type IV (COL4A3, COL4A4, and COL4A5) genes, which will affect the formation of the α3-α4-α5 chain in the collagen IV network. Charcot-Marie Tooth disease (CMT) is the most prevalent inherited peripheral neuropathy, with an incidence of 1 in 2500 individuals. It is characterized by chronic motor and sensory polyneuropathy. CMT has significant genetic and clinical heterogeneity. We present this case to highlight the rare coexistence of two genetic disorders (Alport syndrome and Charcot-Marie-Tooth disease) in the same patient. Recognizing overlapping genetic disorders is essential for accurate diagnosis, multidisciplinary management, and appropriate genetic counseling. A 21-year-old male patient. The condition started at the age of 6 years old when the patient developed persistent hematuria, patient asked for medical advice, investigations revealed hematuria, proteinuria, no skin rash, no arthritis and no history of upper respiratory tract infection, Immune profile (ANA, Anti DsDNA were negative, C3 and C4 were normal, virology (hepatitis scan and HIV Ab were all negative) Antistreptolysin O titer (ASOT) was negative. The renal function test was normal. There was severe bilateral SNHL associated with visual disturbance, with no family history of renal disease. Renal biopsy was done results are suggestive of hereditary nephropathy of Alport type. Patient was maintained on supportive treatment, including an ACEI. Genetic testing: confirmed autosomal recessive Alport syndrome. (homozygous mutation in COL4A4 exon 17). There were associated features that were not consistent with Alport syndrome, like microcephaly, learning difficulties, and poor school performance. At the age of 19 years old, the patient suffered from progressive weakness with continuous muscular pain. He sought medical advice at multiple institutes. Laboratory investigations revealed a high creatinine phosphokinase (CPK) level > 800 U/L. A nerve conduction test was performed, which showed chronic polyneuropathy, with sensory involvement greater than motor involvement, potentially part of hereditary sensory motor polyneuropathy. A likely pathogenic homozygous variant was identified in the SBF1 gene; the result is consistent with a genetic diagnosis of autosomal recessive Charcot–Marie–Tooth disease type 4B3. This case highlights the rare coexistence of Alport syndrome and Charcot-Marie-Tooth disease in the same patient. Recognizing overlapping genetic disorders is essential for accurate diagnosis, multidisciplinary management, and appropriate genetic counseling.