Adrenoleukodystrophy

X-Linked Adrenal Leukodystrophy

X-ALD

1. OMIM:300100

2. Gene:ABCD1

3. Chromosome:X28q

4. Protein:

   1. Acetyl CoA oxidase deficiency

   2. Peroxisome Membrane protein

   3. Needed for transport of very long fatty chains, so they can be processed in the peroxisome to shorter bits that can be used to create more complicated lipids and acetylation of proteins

5. Accumulation: 

• 1. Very long fatty chains

  2. Leads to demyelination in white matter and spinal chord 

6. Test:

• 1. Very long fatty acids in plasma, red blood cells, fibroblasts

  2. Chomosomal studies (preferred method in women)

7. Childhood cerebral type

• 1. Age:5-12 years

  2. Sex:Male

  3. Clinical presentation:

     1. "ADHD"

     2. Visiospatial disturbance

     3. Gait

     4. Possible spinal or periferal symptoms

     5. Slight intelectual impairment

     6. Abnormal pigmentation sometimes

     7. 10% acute:

        1. Siezures

        2. Adrenal crisis

        3. Coma

     8. Eventually:

• • • 1. Hypotonia

      2. Siezures

      3. Swallowing difficulties

• 4. Imaging

• • 1. 80%

       1. Posterior pattern

          1. Typical pattern

             1. Posterior white matter

             2. Central splenium

             3. Corticospinal in pons

             4. Corticopontine in pons

          2. Progression

• • • • • 1. Splenium

          2. Posterior central white matter

          3. Later subcortical

          4. Posterior to anterior

• • 1. 1. 3. Enhancement

• • • • • 1. Zone B

          2. Bad sign

• • 1. 1. 4. Diffusion

• • • • • 1. Restricted in Zone B

• • 1. 1. 5. MRS

• • • • • 1. Active

             1. (-) NAA

             2. (-) myo-Inositol

             3. (+) Choline

             4. (+) Glutamine

             5. (+) Glutamat

             6. (+) Lactate

          2. Chronic

• • • • • • 1. (-) NAA

            2. (+) Choline

• • • • • 3. Predictive, risk for progression in 2-3 years

• • • • • • 1. NAA/Choline under 5.0

• • 2. 15%

• • • 1. Anterior pattern

         1. Genu

         2. Anterior capsula interna

         3. Cerebellar

• • 3. Unilateral lobar or more than lobar

    4. Bilateral genu capsula interna

• 5. Pathology of main type

• • 1. Zone A:Burned out

    2. Zone B:Perivascular demyelination, preserved axons

    3. Zone C:Myelin break down without demyelination

    4. (Zone D): Impending? at least low NAA

8. Adrenomyeloneuropathy

• 1. Age: Mean 28

  2. Sex: Male

  3. Clinical presentation:

     1. Incontinence

     2. Progressive paraparesis

     3. Cerebellar dysfunction

     4. Can be combined with cerebellar involvement

  4. Imaging:

• • 1. Cerebellar white matter

    2. Corticospinal tracts

    3. No enhancement

9. Female heterozygous

• 1. Age:Mean 43

  2. Sex: Female

  3. Clinical presentation:

     1. Like adrenomyeloneuropathy but milder

  4. Imaging:

• • 1. Usually normal 

    2. MRS as compared to normal controls in corticospinal and pareitooccipital

       1. Reduced NAA/Choline

       2. Reduced NAA/Cr

10. Source: Barcovich 5