Prevention and Genetic Testing

Prevention of Adrenoleukodystrophy

There is no way to prevent ALD. Parents who have a history of ALD in their family can undergo genetic counseling when deciding to have a child. By doing this parents are able to get genetically tested to determine if they carry the gene that could be passed on to their offspring. Female carriers can be diagnosed 85% of the time using a very-long chain fatty acid test and a DNA probe study done by laboratories. 

If a child is born with ALD early recognition and treatment may prevent the development of clinical symptoms. Lorenzo’s oil has been shown to be a significant treatment option in young boys. There are also new technologies being developed to allow detection of ALD through newborn screening. A prenatal diagnosis for adrenoleukodystrophy is currently available which evaluated the cells from the chorionic villus or amniocentesis.

Genetic testing for Adrenoleukodystrophy

About 93% of index cases have inherited the ABCD1 mutation from one parent; at most, 7% of individuals with X-ALD have a de novo (Latin expression meaning "from the beginning,") mutation. Affected males transmit the ABCD1 mutation to all of their daughters and none of their sons. Carrier females have a 50% chance of transmitting the ABCD1 mutation in each pregnancy. Males who inherit the mutation will be affected; females who inherit the mutation are carriers and will usually not be seriously affected. Carrier testing of at-risk female relatives and prenatal testing for pregnancies at increased risk are possible if there is a family history of ALD.

CCALD - childhood form ALD
AMN - neurological ALD

References

Hugo W Moser, M.D. Ann B Moser, B.A. Steven J Steinberg, Ph.D. and Stephan Kemp Ph.D. Database X-ald; Adapted from; http://www.x-ald.nl/clinical-diagnosis/genetics-and-counseling/

Moser A., Steinberg J. & Raymond, G. 1999. X-linked Adrenoleukodystrophy. Gene Reviews; Adapted from http://www.ncbi.nlm.nih.gov/books/NBK1315/

Kaneshiro N. & Zieve D. 2009. Adrenoleukodystrophy – Prevention. University of Maryland Medical Center; Adapted from http://www.umm.edu/ency/article/001182prv.htm


Alisha M.

Dietary Management

It is recommended for patients diagnosed with ALD to consume diets low in very-long chain fatty acids (VLCFA) and in conjunction with Lorenzo’s Oil under the supervision of a physician and dietician. Fatty acids are necessary chemicals in the body and can be found in the form of triglycerides, phospholipids, sphingolipids, and glycolipids. All of these forms can be found in cells, or can compose the cell by forming the cell membrane. The body has developed methods on removing fatty acids if they are in excess through the process of β-oxidation. When there is an impairment in the breaking down process, disease often occurs, and in this case, ALD. VLCFA’s are necessary to form parts of the brain membrane, such as myelin. When the body makes too much, and is unable to remove excess amounts, increased levels if C26:0 are seen in ALD.

The normal American diet consists of roughly 12 to 40mg of VLCFA. A study analyzed whether reducing exogenous intake of VLCFA to 3 mg per day would effectively lower C26:0 levels in plasma. Administration of the very long-chain fatty acid restricted diet to 7 adrenoleukodystrophy patients for a 3 to 24 month period was found to be ineffective in lowering plasma VLCFA or in improving clinical status. This may be due to the high endogenous synthesis of C26:0 (demonstrated in fibroblast cells) by elongation of shorter chain fatty acids and may account for failure of dietary therapy.

Hexacosanoic Acid (C26:0)

Plant oils are the richest sources of VLCFA (208mg/100g) while peanut oil has the highest content (tablespoon of peanut oil has 12mg of C26:0). Other foods high in VLCFA are whole-grain or bran cereals, pita bread, and unpeeled fruits (waxes are principal sources). Fish, meats, poultry and eggs contain less than 1mg/100g.

References:

http://www.x-ald.nl/biochemistry-genetics/vlcfa/

Kishimoto Y., Moser HW, Kawamura N, Platt M, Pallante SL, Fenselau C (1980) Adrenoleukodystrophy: Evidence that abnormal very long chain fatty acids of brain cholesterol esters are of exogenous origin. Biochemical and Biophysical Research Communications 96(1): 69-76.

Moser HW, Borel J (1995) Dietary Management of X-linked Adrenoleukodystrophy. Annual Review of Nutrition 15: 379-397.

Van Duyn MA et al. (1984) The design of a diet restricted in saturated very long-chain fatty acids: therapeutic application in adrenoleukodystrophy. The American Journal of Clinical Nutrition 40: 277-284.