Peroxisomal Disorders Flashcards
What physiological functions of the peroxisome?
fatty acid beta oxidation
fatty acid alpha oxidation
bile acid synthesis
plasmalogen
What are peroxisomal biosynthesis disorders?
where either no peroxisome is present or one part is not present so the membrane does not form or the matrix protein does not import properly due to mutations in the PEX genes
Zellweger Syndrome (ZS)
NALD and IRD
RCPP Type I
What is Zellweger Syndrome?
cerebrohepatorenal syndrome
mostly mutation in PEX1
most severe peroxisomal biogenesis disorder resulting in cholestasis, hypotonia, global developmental delay. occular abnormalities (retinitis pigmentosum), seizures, renal cysts, hepatic dysfunction, calcification stippling of patella, perisylvian microgyria
clinical features include large fontanelle, prominent forehead, epicanthal fold, broad nasal bridge
What are NALD and IRD?
less severe peroxisomal biogenesis disorder with later age of onset resulting in developmental delay, hypotonia, sensorineural hearing loss, renal dystrophy, vision impairment, and liver dysfunction
What is RCPP Type I?
peroxisomal biogenesis disorder resulting in facial dysmorphism, short stature, rhizomelia (proximal extremity shortness), cataracts, microcephaly, chondroplasia punctata, and psychomotor retardation
What biochemical markers would indicate a peroxisomal biogenesis disorder?
increased (things broken down by peroxisome): VLCFA (C26 and ratio of C26 to C22), phytanic acid, pristanic acid, bile acid precursors (DHCA, THCA)
decreased (things made by the peroxisome): red cell plasmogen
fibroblast studies: VLCFA levels, C26:0 and pristanic acid beta oxide, phytanic acid alpha oxidation, catalase IF microscopy (diffuse instead of punctate like in normal cells)
List the peroxisomal single enzyme disorders.
fatty acyl-CoA oxidaase 1 (NALD like presentation)
D-bifunctional protein deficiency (ZS like presentation)
Thiolase deficiency (very rare)
Hyperoxaluria type I
Acatalasia
What is XALD?
X-Linked Adrenoleukodystrophy disorder
most common peroxisomal disorder
on NBS because early BMT prior to symptoms is curative)
childhood onset form: decrease in school performance, hyperactive behavior, deafness (central), vision problems, spastic tetraparesis, seizures
adolescent and adult onset forms
What is XAMN?
X-linked Adrenomyeloneuropathy
spastic tetraparesis, pain in legs, sensory ataxia, impaired vibrational sense, sphincter dysfunction
What is RCDP Type I?
defect in PEX7 resulting in no entry of compounds in to the peroxisome, decreasing plasmogen synthesis
What are RCDP Types 2 and 3?
DHAPAT/GNPAT and ADHAP synthase/AGPS respectively
defects in plasmogen synthesis
diagnosed by RBC plasmogen, fibroblast enzymatic studies (DHAPAT, AGPS), and/or molecular genetics
What is Refsum disease?
presents with sensorineural hearing loss, retinitis pigmentosa, ichthyosis, cerebellar ataxia, anosmia, polyneuropathy, cardiomyopathy, skeletal defects
diagnosed by plasma phytanic acid, fibroblast phytanoyl CoA hydrolase, and/or molecular genetics
treated with low phytanic acid diet (which is found in dairy, beef, lamb, and some seafood)
What is Hyperoxaluria Type I?
Alanine Glyoxylate Amino Transferase (AGT) deficiency affecting peroxisome and glycoxylate metabolism resulting in urolithiasis, nephrocalcinosis, renal failure, and oxalosis
What is Acatalasia?
catalase deficiency
disease of peroxisome and oxidative stress
resulting in periodontal infections, oral gangrene, and increased risk of DM
