pediatric demylenating disease

1. ADENOLEUKODYSTROPHY
SAFIA ANDLEEB
LUJAIN ALKHALIFA

2. OBJECTIVES
• Introduction
• Pathophysiology
• Clinical presentation
• Diagnosis
• Treatment
• Prognosis
• Complications

3. INTRODUCTION
• It is a progressive genetic disorder that affects the white matter of nervous
system & adrenal glands
• Falls under the category of leukodystrophies
• X- linked disorder
• Affects Male >>female
• Prevalence is 1 in 20,000 to 50,000 individuals worldwide.

4. PATHOPHYSIOLOGY
• Genetic- ABCD1 mutation on Chromosome X
• Biochemistry- Disruption of Peroxisomal beta-oxidation
Genetic mutation disrupts the biochemical pathway
ABCD1 mutation lack of ABC transporter (ADLP) prevent entry of
VLCFA into peroxisomes no beta-oxidation & breakdown of VLCFA
accumulation in the cells
VLCFA- Very Long
Chain Fatty Acids
VLCFA is toxic to
cells!

5. CNS PATHOLOGY
VLCFA toxicity leads to mitochondrial dysfunction & abnormal calcium
regulation.
Inflammatory demyelination-
• Enlargement of the extra neural space
• Vacuolization & myelin swelling with reactive astrocytes and
macrophage infiltration
• Perivascular lymphocytic and increased permeability of BBB
• Loss of myelin with lipophage formation
• Loss of oligodendroglia and axons
• Dystrophic mineralization

6. CLINICAL
PRESENTATION
Presents in 3 forms:
1. Childhood Cerebral forms
2. Adrenomyeloneuropathy
3. Addison disease

7. CLINICAL
PRESENTATION
Childhood cerebral forms:
• Common:4- 8 years; peak- 7 years
• Rare:< 3 years & >15 years
• Initially -learning disabilities and behavioral problem
• Late stage- severe neurological deficits ( blindness, quadriparesis, visual loss,
cerebellar ataxia, seizure)
• Adrenal insufficiency- hyperpigmentation
• Rapid progression- disability in 6 months – 2 years.

8. CLINICAL
PRESENTATION
Adrenomyeloneuropathy:
• Typically in adults (male) between 20- 40 years of age
• Spinal Cord dysfunction & peripheral neuropathy: progressive stiffness,
spastic paraparesis, abnormal sphincter control, sexual dysfunction.
• Adrenal insufficiency
• Progressive Cerebellar disorder- Ataxia
• Cerebral involvement in long- term
Degenerative axonopathy (Wallerian degeneration) + 2ndry myelin loss
Involvement of fasciculus gracilis & lateral corticospinal tract

9. CLINICAL
PRESENTATION
Addison Disease only :
• 10% of ALD patients ( typically mildest of all)
• Adrenal insufficiency: unexplained vomiting, weakness and coma,
hyperpigmentation.
• No neurological signs and symptoms.
• Usually present before 8 years of age ( can occur in adulthood)
• Biochemical evidence can be present 2 years prior to clinical signs and
symptoms.

10. CLINICAL
PRESENTATION
Atypical presentation:
• Account for 5-10% of presentation
• Headache & increased ICP with focal signs in age group 4-10 years
• Progressive paralysis, dementia & behavioral changes in adult
• Progressive incoordination or ataxia in a child or adult
• Only erectile dysfunction with FMHx of ALD
• Asymptomatic
Female Carriers:
• Typically AMN phenotype – peripheral neuropathy & myelopathy
• Present with gait disturbance, fecal incontinence & mild spastic paresis
• Rarely adrenal insufficiency or cerebral disturbance
• Less severe than male.

11. DIAGNOSIS
• Measuring the level of the VLCFD in the blood.
• Adrenal function
• Genetic testing of ALD mutation on the ABCD1
• Brain MRI specific changes in the white matter can be detected
• Prenatal testing  10-12 weeks by CVS

12. TREATMENT
• Steroid for adrenal insufficiency .
• Leranzo’s oil to decrease the level of VLCFD
• Bone marrow transplant
• Physical therapy
• Switching diet to low consumption of VLCFD
• Symptomatic relief

13. PROGNOSIS
• Childhood ALD usually have a very rapid course. Symptoms
typically progress very fast and these children usually become
completely incapacitated and die within three to five years of the
onset of symptoms.
• The symptoms of AMN progress slowly over decades. Most
affected individuals have a normal lifespan.

14. COMPLICATIONS
• Adrenal crisis
• Vegetative state (Long term Coma)

15. REFERENCES
• Adrenoleukodystrophy,-Alan K Percy, Ronald JA Wanders- Uptodate
• Causes and clinical manifestations of primary adrenal insufficiency in
children- uptodate
• Facts on ALD – Marc Engelen & Stephan Kemp
• X- linked Adrenoleukodystrophy- Genetic Home Reference
• Entry 300100: Adrenoleukodystrophy, (ALD)." OMIM—Online Mendelian
Inheritance in Man. (May 9, 2004.) <http://www.ncbi.nlm.nih.gov/htbin-
post/Omim/dispmim?300100>. Moser, Hugo W., Anne B. Moser, and Corinne D.
Boehm. "X-linked Adrenoleukodystrophy." March 9, 1999 (May 9, 2004).
University of
Washington, Seattle. GeneClinics.<http://www.geneclinics.org/profiles/x-
ald/>.
• Karen M. Krajewski, MS, CGC
• Rosalyn Carson-DeWitt, MD
• Google images