Pathogenetic Considerations

The biochemical findings of an isolated accumulation of VLCFA in the absence of abnormal bile acid intermediates are consistent with an isolated deficiency of fatty acyl-CoA oxidase. Bile acid intermediates have their own CoA oxidase, whereas bifunctional protein and thiolase are active for all substances ß-oxidized in peroxisomes. The gene encoding acyl-CoA oxidase or palmitoyl-CoA oxidase, ACOX1, is located on chromosome 17q25.

Two peroxisomal disorders, peroxisomal acyl-CoA oxidase deficiency (pseudo-NALD) and X-linked adrenoleukodystrophy, are characterized by an isolated accumulation of VLCFA. It is striking that both disorders may lead to demyelination with inflammation, as suggested by the contrast enhancement on neu-roimaging. There are, however, also important differences. Patients with acyl-CoA oxidase deficiency display clinical abnormalities from birth on, while the clinical symptoms start much later in X-linked adrenoleukodystrophy. In acyl-CoA oxidase deficiency, the ß-oxidation of C22 unsaturated fatty acids by chain-shortening and the ß-oxidation of dicarboxylic acids are deficient in addition to the oxidation of VLCFA, such as C24:0 and C26:0 fatty acids. In X-linked adrenoleukodystrophy only the ß-oxidation of the VLCFA is deficient. These differences may be important in explaining the clinical differences.

Adrenoleukodystrophy

Fig. 20.1. A 3-year-old female patient with isolated peroxiso- white matter.The pyramidal tracts in the posterior limb of the mal acyl-CoA oxidase deficiency.Note the signal abnormalities internal capsule are affected. From Suzuki et al. (2002), with in the corticospinal tracts in the brain stem and the cerebellar permission

Fig. 20.1. A 3-year-old female patient with isolated peroxiso- white matter.The pyramidal tracts in the posterior limb of the mal acyl-CoA oxidase deficiency.Note the signal abnormalities internal capsule are affected. From Suzuki et al. (2002), with in the corticospinal tracts in the brain stem and the cerebellar permission

20.4 Therapy

No specific treatment is available. Supportive care is important.

20.5 Magnetic Resonance Imaging

In several patients CT scan of the brain was performed at birth and found to be unremarkable. No evidence of cortical malformation was seen, although minor or mild abnormalities in gyration and hetero-topias can easily be missed on CT. Repeat CT after the onset of neurological deterioration reveals symmetrical white matter hypodensities in the centrum semiovale and the occipital area with contrast enhancement of the border of the lesions. The CT findings are reminiscent of those reported in neonatal adrenoleuko-dystrophy.

MRI soon after the onset of neurological deterioration shows signal abnormalities in the cerebellar white matter, brain stem tracts, and middle cerebellar peduncles (Figs. 20.1 and 20.2). On follow-up, the pyramidal tracts at higher levels of the brain stem and the posterior limb of the internal capsule become abnormal in signal. Subsequently signal changes develop in the periventricular parieto-occipital white matter and the splenium of the corpus callosum (Figs. 20.2 and 20.3), spreading outward and forward, finally involving also the frontal white matter. If contrast is administered,enhancement is expected. No evidence of a migrational defect has been reported.

Corpus Callosum Defect

Fig. 20.2. The first two rows show the images of a male patient with peroxisomal acyl-CoA oxidase deficiency at the age of 3 years and 5 months. There are extensive signal abnormalities in brain stem tracts,middle cerebellar peduncles,and cerebellar white matter.There are incipient signal changes in the parietooccipital white matter. The third row shows the images of

Fig. 20.2. The first two rows show the images of a male patient with peroxisomal acyl-CoA oxidase deficiency at the age of 3 years and 5 months. There are extensive signal abnormalities in brain stem tracts,middle cerebellar peduncles,and cerebellar white matter.There are incipient signal changes in the parietooccipital white matter. The third row shows the images of the same patient at the age of 7 years and 11 months.The posterior limb of the internal capsule,parieto-occipital white matter, and splenium of the corpus callosum now display prominent signal abnormalities. From Suzuki et al. (2002), with per-

Occipital Lymph Node Mri

Fig. 20.3. Female patient with peroxisomal acyl-CoA oxidase deficiency at the age of 3 years and 3 months. Tracts in the brain stem (especially the corticospinal tracts), cerebellar white matter,hilus of the dentate nucleus,posterior limb of the internal capsule, thalamus, parieto-occipital white matter,and

Fig. 20.3. Female patient with peroxisomal acyl-CoA oxidase deficiency at the age of 3 years and 3 months. Tracts in the brain stem (especially the corticospinal tracts), cerebellar white matter,hilus of the dentate nucleus,posterior limb of the internal capsule, thalamus, parieto-occipital white matter,and splenium of the corpus callosum are affected. In addition, there is some generalized cerebral atrophy.The images resemble those of the cerebral form of X-linked adrenoleukodystro-phy. From Suzuki et al. (2002), with permission

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Responses

  • ky
    Where are occipital lymph nodes?
    8 years ago
  • Ghenet
    What is the occipital lymph node connected to?
    7 years ago
  • terhi
    What is adrenoleukodystrophy?
    7 years ago

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