[Ocular findings in Fabry's disease]

Abstract

Introduction: Fabry's disease is a recessive X-linked disorder that results from a deficiency of the lysosomal hydrolase a-galactosidase A (alpha-Gal A). The absence of alpha-Gal A enzyme activity leads to accumulation of glycosphingolipid globotryaosyl ceramide (GL-3) in the lysosomes of a variety of cell types. Subsequently, angiokeratoma and ocular signs develop until, in most cases after the third decade of life, severe renal dysfunction or cardiomyopathy becomes obvious. Corneal opacities (cornea verticillata) occur in 90% conjunctival vascular changes in 60%, retinal vessel tortuosity in 55%, and cataracts in 50% of cases. Recently, enzyme replacement therapy has been shown to be an effective treatment modality that can eliminate glycolipid stores and reverse the disease pathology.

Case report: A male patient born in 1971 was admitted for clinical examination due to proteinuria and erythrocyturia. During further evaluation nephrologist suspected Fabry's disease, because patient had skin changes early referred as petechiae, and acroparesthesias. He had also low heat tolerance and virtually no sweat. Physical status: angiokeratoma on gluteat regions and upper arms. Urine analysis in several occasions 10-15 E in sediment, alb. positive. On ECG, 2-mm depression of ST in precordial region. Heart ultrasound: low mitral regurgitation angio stage 1, left ventricle hypertrophy. Abdomen ultrasound: both kidneys around 12 cm large, parapyelic cysts in both kidneys of 2.5 cm in diameter. Biomicroscopy of both eyes: cornea verticillata. Fundus of both eyes: papillae n. optici with poorly defined edges, but without prominence, very tortuotic retinal blood vessels. In March 2002, very low alpha GAL enzyme activity in blood (alpha-Gal A = 0.5 +/- 0.2 nmol of substrate hydrolyzed hourly per serum mL--normal serum enzyme level 8.5-18.9 nmol/mL/h). In May 2002, enzyme replacement therapy was started with recombinant alpha-Gal A enzyme (Fabrazyme) 1 mg/kg every 14 days. Control evaluation and examination showed good cardiac and renal function. The patient felt better and stronger with improved heat tolerance.

Conclusion: Fabry's disease occurs in all ethnic groups. It is estimated that one in 200 people is a carrier, and one in 40,000-100,000 has the disease. Today in Croatia, Fabry's disease has been diagnosed in only one patient, and according to the usual prevalence there are still 45-100 unrecognized patients. The ophthalmologists are in excellent position to diagnose Fabry's disease in early stages. Therefore it is very important that the ophthalmologists in Croatia become aware of the importance of ocular findings in Fabry's disease, so they can participate in the identification of unrecognized patients.