Peroxisomes are spherical 1pm diameter organelles with a multitude of oxidative and other enzymes packed within a single-layered membrane (http://www.peroxisomedb.org)
- global' peroxisomal disorders with impaired peroxisomal biogenesis (fewer or even no peroxisomes), together with those single peroxisomal enzyme defects that induce a similar phenotype (in particular, D-bifunctional protein deficiency)
- adrenoleukodystrophy, due to an X-linked defect of the peroxisomal ABCD1 gene that codes for the peroxisomal membrane protein ABCD1, a member of the ATP-hmding cassette transporters.
While estimation of very long chain fatty acids (VLCFA) may detect many peroxisomal isomers there is no 'metabolic screen' that will detect them all.
CLINICAL CLUES TO PEROXISOMAL DISORDERS
- Neonatal hypotonia (especially extreme hypotonia of the neck) Neonatal seizures (refractory or phenytoin-responsive in a hypotonic baby)
- Neonatal unresponsiveness (except reflex crying)
- Non-development
- Retinal blindness ('Leber amaurosis')
- Sensorineural deafness
- Gross dysmorphic features of Zellweger syndrome type (high forehead, flat face, simian creases, simple genitalia)
- Mild dysmorphism (large fontanelle with open metopic suture, absent ear lobules)
- Leukodystrophy, neuronal migration defects especially perisylvian polymicrogyria
- Hepatomegaly (± hepatic insufficiency)
- Developmental delay with malabsorption features, retinopathy and sensorineural deafness
- Development delay with seizures and areflexia (peripheral neuropathy).
- School-age regression in a boy with previously normal development (+ Addison disease)
- Spastic paraplegia in older females.
Investigation results found in peroxisomal disorders
In neonatal and early manifesting peroxisomal disorders