No accumulation of globotriaosylceramide in the heart of a patient with the E66Q mutation in the α-galactosidase A gene

Fabry disease is an X-linked lysosomal disorder resulting from mutations in the α-galactosidase A (GLA) gene. Recent reports described that the E66Q mutation of GLA is not a disease-causing mutation. However, no pathological study was reported. We carried out pathological studies using a cardiac biopsy specimen from a patient with the E66Q mutation. The case was a 34year old male patient with end-stage renal failure and cardiomegaly. He was diagnosed with gout at 15years of age and hemodialysis was started for gouty nephropathy from 31years of age. He was suspected of having Fabry disease as the result of a screening study for Fabry disease in patients with end-stage renal failure and was referred to our hospital for mutation analysis of the GLA gene. We carried out enzymatic and genetic analysis for GLA and pathological studies of a cardiac biopsy specimen. The patient had the E66Q mutation in the GLA gene. GLA activity in leukocytes was 36.2% of the average of normal controls. The pathological study of the cardiac biopsy sample showed no characteristic findings of Fabry disease. The immunohistochemistry for GL3 of the cardiac biopsy sample showed no positive cells. Although the E66Q mutation reduced enzyme activity, the characteristic pathological findings of Fabry disease and the abnormal accumulation of GL3 were not detected in cardiac tissues. The E66Q mutation of the GLA gene is thought to be a functional polymorphism based on enzymatic and pathological studies. ► We studied a male patient with E66Q mutation in GLA gene. ► The GLA activity of the study patient was higher than that of Fabry patients. ► The pathological studies of the patient showed no Fabry characteristic findings. ► The GL3 immunohistochemistry of the patient's tissue showed no GL3 accumulation. ► The E66Q mutation in the GLA gene was thought to be a functional polymorphism.