irreversible multiorgan damage.Since early childhood, he had experienced acroparesthesias precipitated by heat or physical exertion.He developed proteinuria in his teens and underwent a kidney biopsy at the age of 20, which revealed focal segmental glomerulosclerosis.An angiotensin II receptor blocker was initiated, but his renal function gradually deteriorated, and hemodialysis was started at the age of 30.He had recurrent transient ischemic attacks and left ventricular hypertrophy was subsequently noted during his 30s.At the age of 37, a newly appointed physician with experience in managing FD suspected the disease and referred him to our hospital.He had a family history of childhood-onset acroparesthesias in his mother and aunt, which resolved as they matured.-galactosidase A activity was markedly reduced to 1.5 nmol/h/mL, and genetic analysis revealed the presence of the classical phenotype.He was diagnosed with FD based on his clinical manifestations, family history, and -galactosidase A enzyme activity.Enzyme replacement therapy (ERT) with agalsidase was initiated, leading to gradual improvement of his acroparesthesias.However, six months following the start of ERT, he experienced an ischemic stroke, and similar events recurred frequently.Consequently, his ERT was switched from agalsidase to agalsidase at the age of 38.Nevertheless, multiple ischemic strokes continued to occur, leading to gradual cognitive decline and the development of gait disturbance.In addition, serial echocardiographic evaluations demonstrated a marked progression of left ventricular hypertrophy.Two and a half years after the initiation of ERT, at the age of 40, he died due to cardiac arrest secondary to atrial fibrillation, and a pathological autopsy was performed.Results: Macroscopic examination revealed concentric left ventricular hypertrophy of the heart, marked renal atrophy with cystic changes, and extensive white matter necrosis in the brain.Histologically, myocardial smooth muscle cells exhibited significant cytoplasmic vacuolization, while glomerulosclerosis, tubular atrophy, interstitial infiltration, and numerous casts were observed in the kidneys.Vacuolation of brain parenchymal cells and intimal thickening of cerebral blood vessels were noted.Electron microscopy identified zebra bodies in both myocardial and renal cells.Conclusion: A pathological examination confirmed irreversible organ damage, which was likely responsible for the limited efficacy of ERT in this case.This case highlights the importance of early diagnosis and treatment in FD.I have no potential conflict of interest to disclose.I did not use generative AI and AI-assisted technologies in the writing process.
Sambitan et al. (Wed,) studied this question.