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-X-linked
-a-galactosidase A deficiency
--this is an enzyme that breaks down globotriaosylceramide (Gb3), which is a sphingolipid also known as ceramide trihexoside.
Accumulates in:
-Vascular smooth muscle cells
-Glomerular/distal tubule cells
-Cardiac myocytes
-Dorsal root and autonomic ganglia
Presentation:
-Neuropathic pain
-Hypohidrosis
-Severe distal extremity pain, burning
-Distal loss of hot/cold temp sensation.
-Angiokeratomas (dark red, non-blanching macules and papules that classically occur in clusters over the buttocks, groin, and umbilicus)
-Telangiectasia
-Cerebrovascular (eg, transient ischemic attack, stroke) and cardiac (eg, left ventricular hypertrophy) diseases (most common causes of death)
-Gb3 buildup in the glomerulus and distal tubule results in proteinuria and polyuria, respectively, and can progress to renal failure in the absence of enzyme replacement therapy
Excacerbating symptoms:
-Exercise
-Stress
-Fatigue -autorecess
-deficiency of phenylalanine hydroxylase or deficiency of tetrahydrobiopterin cofactor (BH4)
-A disorder of aromatic amino acid metabolism.
-Tyrosine becomes essential
-↑ phenylalanine → excess phenylketones in urine
--phenylketones = phenylacetate, phenyllactate, phenylpyruvate.
-Patient's can't metabolize Isoleucine, Leucine, Methionine, Serine
-Pts have intellect disability, growth retardation, seizures, fair skin (albinismy), eczema, musty body odor (from phenylketones)
Treatment
-↓ phenylalanine and ↑ tyrosine in diet. tetrahydrobiopterin supp.
-avoid aspartame (contains phenylalanine) ;
