© 2017

By Keith S. Wexler, MBA, Maternal Fetal Medicine, Prenatal Diagnosis and Biotech/Life Sciences Consultant, GENASSIST, Inc.

Paul Wexler, M.D., F.A.C.O.G., Medical Director, GENASSIST, Inc.

Clinical Professor, Department of OB/GYN, University of Colorado Health Sciences Center

Clinical Professor, Division of Genetics/Dept. of Pediatrics, Univ. of Colorado/The Children’s Hospital

Adrenoleukodystrophy (ALD) is an X-linked fatal disease that affects the brain’s nerve cells and the adrenal glands with an incidence of approximately 1:20,000 to 1:50,000.  Severity can vary in family members.

Since ALD is an X-linked Disease: 50% of males will be affected if they inherit the carrier X chromosome from a carrier mother, 50% of females would be carriers.

Some females can exhibit symptoms but they usually occur later and are milder. Most affected females inherit their X chromosome from a father with the disease.

There are three major types of Adrenoleukodystrophy (ALD):

  • Childhood ALD: Onset age 4 to 10 years. Symptoms: Learning problems, behavioral problems, aggression, vision problems, difficulty with coordination and swallowing and decreased adrenal function. Life expectancy: Variable, usually 1-10 years.
  • Adrenomyeloneuropathy: Onset age young adult to middle age (usually 20- to 35 years of age) . Symptoms: Stiffness and weakness in legs, urinary and/or genital function problems, changes in thinking and behavior and usually changes in adrenal cortex function. Life expectancy is average.
  • Addison Disease Only – Hypoadrenocorticism (Mildest Form): Onset age childhood to adulthood. Symptoms: Adrenal cortex insufficiency. Usually adrenomyeloneuropathy by middle age.

http://www.stopald.org/what-is-ald/

Over 600 mutations in the ABCD-1 (ATP-Binding Cassette Transporter) gene which directs the formation of the adrenoleukodystrophy protein (ALDP) and is located in eroxisomes on the long arm of the X chromosome (Xq28) causes an increase in the very long chain fatty acids (VLCFA) in the body, primarily in the brain and adrenal cortex, which is toxic to the adrenal cortex and causes an inflammatory response to myelin.

The prognosis for patients diagnosed with ALD is very variable.

Childhood ALD is progressive with life expectancy usually 1 to 10 years.

Chemotherapy and bone marrow transplantation has been tried and a new gene therapy PRCN-323 using an adeno-associated virus which is injected into the spinal fluid is in trials.