Diagnostic insights from a case of Fabry disease presenting with IgA nephropathy-like changes and familial cardiomyopathy

A 39-year-old male patient was admitted on 29 January 2026 due to long-term hypohidrosis (over 20 years), proteinuria (self-discontinuation of medication following IgA nephropathy diagnosis), and newly identified significant cardiac hypertrophy. The patient also had a history of intermittent diarrhea and a suspected family history (his mother had been diagnosed with “hypertrophic cardiomyopathy” and had a pacemaker implanted). Physical examination revealed cutaneous angiokeratomas. Laboratory tests indicated renal impairment and proteinuria, while echocardiography and cardiac magnetic resonance imaging both showed pronounced concentric left ventricular hypertrophy with reduced global longitudinal strain (GLS). Based on the multisystem involvement (neurological, cutaneous, renal, and cardiac), Fabry disease was clinically suspected. Subsequent enzymatic testing confirmed significantly reduced α-galactosidase A (GLA) activity and markedly elevated plasma globotriaosylsphingosine (Lyso-Gb3) levels. Genetic analysis identified a novel frameshift mutation, c.204_205del (p.Phe69Hisfs*18), in the GLA gene. Genetic testing of the patient's mother confirmed that she carried the same mutation and had more severe cardiac involvement, thereby correcting her long-standing misdiagnosis. This case illustrates the chronic underdiagnosis and misdiagnosis of Fabry disease resulting from the fragmented interpretation of its multisystem manifestations. It underscores the critical importance of specific enzymatic and genetic screening in patients with unexplained left ventricular hypertrophy accompanied by extra-cardiac manifestations and a suggestive family history. Furthermore, the discovery of a novel mutation enriches the genetic spectrum of the disease and highlights the essential role of cascade family screening in identifying affected individuals and guiding early intervention.