Peroxismal biogenesis defects: (peroxisome = a oxidation of some FA in cytoplasm b4 going to B

oxidation in mitochondria)

All dzs in this category affect myelin (leukodystrophy), all are XR

1.Zellweger spectrum : zellweger syndrome(severest) , NALD ,IRD(least severe)

CNS+dysmorphysim (high forehead, up salnting palpepral fissure, hypoplastic orbit epicanthal fold, wide
fontanelles)

2.Rhizomelic chondrodysplasia punctata (RCDP):

Shortening of proximal extremities, nasal hypoplasia, vertebral cleft, abn enchondrial bone formation,
epiphyseal stippling.

Zellweger syndrome: severest form, aka: cerebrohepatorenal :

CNS: vision(retinitis pigmentosa, hearing dysfx, seizures, retardation)

Dysmorphism

Prx at birth  not live >1yr

NALD: mod form, CNS, dysmorphism (may not be prx)

Prx at birthmay live up to mid teens

XALD: enzyme defect, ABCD1 gene defect(ATPase binding cassette

subfamily D)

Prx:4-10y.o adrenomyeloneuropathy +/- cerebral involve.

So screen all children with adrenal insuff. With VLCFA level

Infantile refsum dz: mild form, CNS , dysmorphism(usually not prx), prx: in 1 st yr

Classical refsum dz: enzyme defect:phytanoyl co A hydroxylase def.

no dysmorphism, but ichthyosis may develop later in pts , prx: late
childhood/ early adolescence .

Dx: All the mentioned dz: VLCFA, BCFA (phytanic acid ) are elevated.
Lysosomal storage dzs: (recycling center of cell)all are XR except Hunter and Farby dzs

1.Mucopolysaccharidoses: glycosamineglycans(heparin, dermatan sulfate) are elevated, and usually

assoc with coarse facial features.

Hurler syndrome: a-L iduronidase def. CNS , corneal clouding+, somatic features , dystosis multiplex
( abn calvaria, bones , vertebra),gargoylism, prx: 4-18mos

Hunter syndrome: iduronate sulfatase def.), CNS, but no corneal clouding somatic features:( coarse
facial features,short stature, skeletal deformities, HSM, large tongue, aggressive behavior. Prx:2-4 yr.(a
hunter should see clearly)

San filippo: limited somatic features but severe CNS dz , start as behavioral abn: aggression, sleep ds.
Then prog. Prx: 2-6yr

2.Glycolipids degredation defects:( sphingolipidoses) :

GM1 : Bgalactosidase def.  GM1 gangliosides acc. Prx: 3-6mos : corneal clouding, cherry red spot on
macula, coarse thick hair, depressed nasal bridge, gingival hypertrophy , low set ears, hair on forehead.

Tay sachs: (GM2 gangliosidosis) : B hexosaminidase def. (a sub unite) GM2 gangliosides acc. Prx: 3-
6mos, cherry red spot, death by 3y.o

Sandhoff: B hexosaminidase def. (B sub unite)  (GM2 gangliosidosis ) :prx: 3-6 mos , cherry red spot ,
death by 3 y.o

Gaucher : acid B glucosidase (B glucocerebrosidase)  glucocerebroside(glucosylceramide) acc.

Prx: infantile , juvenile or adult type : CNS, HSM, BM (plt dec., WBC dec., anemia), gaucher cells(lipid
engorged mQ+wrinkled tissue paper app.), avascular necrosis of femor head, flask Erlenmeyer deformity

Nieman pick: sphingomyelinase def  sphingomyelin acc. Prx: 4-6 mos HSM, CNS cherry red spot.

Fabry dz: a galactosidase def  ceramide trihexoside acc  deposite in vessel wall, XLR , prx: childhood
or adolescence , pain + paresthesia in ext’s, GI syx, CMP, prog. Renal failure. Cataract,
angiokeratoma(red skin skin lesions).

Farber dz: acid ceramidase def  ceramides acc, Prx: 1 mos death by 2 yr, painful distorted joints ,
subcutaneous nodules( granuloma + lipid laden mQs) , hoarseness, CNS, HSM, heart, lung. +/- red cherry
spot

Krabbe dz: galactocerebrosidase def galactocerebroside acc. Aac of multinucleated globoid cells in
brain (globoid cell leukodystrophy) , prx: 3-6 mos , optic atrophy …… death 2 yr (only CNS).

Metachromatic leukodystrophy: aryl sulfatase def  sulfatide acc. Prx: late infantile 6mos-4yr, juvenile
4yr- puberty , adult :after puberty . deterioration in school performance , walk abn, ataxia …..death
<20y.o, metachromatic staining of nerve sheath.