Pathophysiology

1) type of lysosomal storage disease 2) cause is defect (multiple types possible) in alpha-galactosidase with altered metabolism of glycosphingolipid 3) onset is in childhood

Signs and Symptoms

1) angiokeratomas (telangiectasias of skin) that are blue-black to red and do not blanch – they increase in size and number as patient ages and are most dense on upper legs 2) acroparesthesias 3) small vessel disease of the brain, heart, and kidneys 4) hypohidrosis 5) abdominal pain that is worse with stress or fatigue 6) early coronary artery disease 7) lens and corneal opacities 8) leg lymphedema 9) episodic diarrhea 10) arthropathy of finger joints

Characteristic Test Findings

Laboratory – 1) hematuria 2) proteinuria

Histology/Gross Pathology

1) cellular accumulation of trihexosylceramide (THC), especially in endothelium 2) characteristic myeloid bodies seen on kidney biopsy

Associated Conditions

1) renal failure 2) leg lymphedena 3) hypertension 4) left ventricular hypertrophy 5) angina 6) congestive heart failure 7) stroke 8) focal segmental glomerulosclerosis 9) restrictive cardiomyopathy

Biochemistry

alpha-galactosidase A enzyme cleaves the terminal end of THC, which is a step in the metabolism of glycosphingolipid

Inheritance/Epidemiology

1) X-linked disorder (GLA gene on Xq22) 2) occurs in 1/40,000 3) most severe in men – heterozygous females have some symptoms but lack the severe organ involvement

Treatment

1) phenytoin and carbamazepine decrease the acroparesthesias 2) hemodialysis and kidney transplantation for renal failure 3) enzyme therapy

Tips for USMLE

angiokeratomas tend to be most numerous on thighs