Fabry disease
General description
Fabry disease is caused by a deficiency in α-galactosidase activity, leading to the accumulation of its substrate, globotriaosylceramide, in various tissues, including vascular endothelial cells, sweat glands, kidneys, smooth muscle cells, myocardium, the nervous system, and corneas. This accumulation results in complications such as renal damage, cerebrovascular disease, ischemic heart disease, cardiomyopathy, and corneal opacity. Although it is an X-linked recessive disorder, heterozygous females can also be affected.
Clinical manifestations
Fabry disease presents with a wide range of symptoms that typically begin in childhood and progressively affect multiple organ systems into adulthood. The most common early symptom is acroparesthesia—burning or tingling pain in the hands and feet, often triggered by exercise, fever, or temperature changes.
Characteristic skin findings include angiokeratoma corporis diffusum—clusters of dark red or purple vascular lesions, usually between the umbilicus and knees. Eye involvement is marked by corneal verticillata, a whorl-like pattern seen on slit-lamp exam. Autonomic symptoms such as reduced or absent sweating (hypohidrosis or anhidrosis) occur.
Gastrointestinal symptoms—including abdominal pain, diarrhea, constipation, early satiety, and nausea, can significantly reduce quality of life. Kidney involvement is a major concern, beginning with proteinuria and potentially progressing to end-stage renal disease. Cardiac issues include left ventricular hypertrophy, arrhythmias, valve problems, and heart failure. Neurological features include hearing loss, tinnitus, vertigo, and an elevated risk of stroke at a young age.
Lacunar infarction
The MRI findings and clinical descriptions indicate a vascular disease with multiple neurovascular complications affecting the central nervous system. MRI (T2-weighted and FLAIR) shows high-signal areas in the cerebral white matter and basal ganglia, consistent with multiple lacunar infarcts.
Cerebral atrophy
Posterior artery dilation
Neuroimaging reveals significant abnormalities affecting the cerebral vasculature, particularly in the posterior circulation system.
Pulvinar sign
The deep gray nuclei demonstrate characteristic abnormalities in Fabry disease, with the pulvinar thalami showing distinctive T1 hyperintensity that was previously considered pathognomonic for the condition. However, recent evidence suggests these T1 hyperintensities more likely represent calcium salt deposits rather than glycosphingolipid accumulation.