Adrenoleukodystrophy

1
Adrenoleukodystrophy

• A genetic disorder affecting 1 out of every
  21,000 young boys between the ages of 4 and 10

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What is ALD?

• An error on the X Chromosome
• ABCD1 Gene can not code for an enzyme that breaks
  down very long chain fatty acids (VLCFA)
• Causes Build up of VLCFA in the nervous system,
  adrenal cortex, and plasma
• Demyelinization results and adrenal insufficiency
  results

3
Demyelinization

• Myelin is the smooth coating around the axons of
  neurons
• Allows the neurons to send and receive messages
  quickly

4
Early Stage Symptoms

• Onset Usually occurs around the ages of 4 and 6
• Attention, behavioral, and cognitive problems.
• Progresses into minor motor and coordination
  problems.
• Examples Not paying attention at school, falling
  off bike, or having trouble making sentences.

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Devastation

• Full symptoms
• The boy in question eventually has frequent
  seizures and becomes blind, deaf, mute, and
  immobile
• The demyelization of the nervous system is to
  blame
• Death soon follows
• If Untreated, boys will not reach their teenage
  years

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Testing Ahead of Time

• The best time to screen the ABCD1 gene is in the
  potential mother
• Prenatal genetic testing is available
• Infants can also be genetically screened

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Importance of Screening Infants

• ABDC1 gene on the X chromosome can undergo random
  mutation
• About 7 of boys with ALD did not have mothers
  with the genetic defect.

8
Diagnostic Tools Used During Onset of ALD

• MRI is the first lead for physicians
• MRI is abnormal in ALD boys
• Testing plasma for VLCFA levels
• High levels of VLCFA is a compelling clue
• Chromosomal analysis solidifies ALD diagnosis

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How Come Girls Do Not Get ALD?

• Girls are only carriers of the genetic defect.
• The disorder is recessive so the other
  X-chromosome acts as a mask over the defect.
• Males only have one X chromosome and therefore
  can not hide the disease.

10
Treatments

• Bone Marrow Transplant
• Used when diagnosed early
• Can be dangerous and is used cautiously
• Adrenal Steroid Replacement Therapy
• Does not reduce progression of nervous system
  damage
• Only assists with the fraction of the disease
  that causes adrenocortical insufficiency

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Treatments Continued

• General support from parents
• Psychological support
• Physical therapy
• Special education

12
Experimental Treatments

• Dietary Therapy
• Mixture of glyceryl trioleate, glyceryl
  trierucate, lovastatin and 4 phenylbutyrate
• Lorenzos Oil
• Mixture of oleic acid and erucic acid (made from
  olive and rapeseed oil)

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Lorenzos Oil

• Highly publicized in a 1992 film starring Susan
  Sarandon and Max Nolte

14
How Does it Work?

• The body accumulates VLCFA via diet and
  biosynthesis
• Lorenzos Oil shuts off the biosynthesis of VLCFA
  via competitive inhibition
• The VLCFA and monounsaturated fats are elongated
  by one enzyme. Lorenzos Oil contains
  monounsaturated fatty acids that compete with the
  VLCFA for use of the enzyme. Thus, when Lorenzos
  Oil is added to the diet, VLCFA levels decrease
  and the harmless monounsaturated fatty acids
  increase.

http//www.myelin.org/aboutoil.htm
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Ethical Questions

• Will prenatal testing lead to abortions of
  affected fetuses?
• Will insurance agencies have access to genetic
  screening results?
• How will insurance agencies handle treatment
  options?
• With the advancement of treatment options, what
  will happen when boys affected with ALD reach
  maturity and can procreate?
• This can lead to females having ALD. Is this fair
  to the potential daughter and will treatments
  work the same on females?