A 7-year-old boy was diagnosed with atypical hemolytic uremic syndrome (aHUS) after abdominal pain, vomiting, edema, microvascular hemolytic anemia, thrombocytopenia, acute kidney injury, and hypocomplementemia. Treatment included pulse methylprednisolone, cyclophosphamide, mycophenolate mofetil, and infusion of fresh frozen plasma, resulting in remission. Numbness of the fingers and pain in the toes with fever developed at the age of 12 years. At the age of 17, he had worsening toe pain, renal dysfunction (creatinine 156 μmol/l, eGFR 38.4 ml/min/1.73 m²) and left ventricular hypertrophy with outflow tract obstruction. Screening for Fabry disease (FD) confirmed reduced alpha-galactosidase A activity (<1.00 μmol/l/h) and gene variant c.611G>A (p.Trp204Ter). Exome sequencing of the family revealed a MYH7 variant (c.1063G>A, p.Ala355Thr), the father had hypertrophic cardiomyopathy (HCM). Despite enzyme replacement therapy, FD's renal function progressed to stage 5 CKD and cardiac hypertrophy did not improve after 2 years. The case illustrates the diagnostic challenges in the comorbidity of aHUS, classic FD, and HCM with a genetic background.