Adrenoleukodystrophy, or ALD, is a rare genetic condition that can impact the nervous system and the adrenal glands. It arises from a specific genetic mutation that disrupts the body’s ability to break down very-long-chain fatty acids (VLCFAs). This accumulation of fats primarily affects the myelin, the protective sheath covering nerve cells, and can lead to a range of neurological issues. For expectant parents, particularly when the mother knows she is a carrier of the genetic trait, understanding the implications of ALD during pregnancy is a primary concern.
The Genetics of ALD Inheritance
Adrenoleukodystrophy is classified as an X-linked disorder, which means the gene responsible for it, the ABCD1 gene, is located on the X chromosome. Chromosomes are the structures that hold our genetic information, and the X and Y chromosomes determine a person’s sex. Females have two X chromosomes, while males have one X and one Y chromosome, and this difference is central to how ALD is inherited.
A mother who carries the mutation has a 50% chance of passing that specific chromosome to each of her children. Since males have only one X chromosome, inheriting the one with the ABCD1 mutation means they will have ALD, as there is no second, healthy X chromosome to compensate. If a female child inherits the affected X chromosome from her mother, she will also receive a healthy X chromosome from her father. This second, functional copy of the gene protects her from developing the most severe forms of the disease, and she becomes a carrier.
Potential Effects on the Fetus
A male fetus that inherits the mutated ABCD1 gene will be born with ALD. While these infants appear healthy at birth, they carry a significant risk for developing serious health problems as they grow. The most concerning of these is the childhood cerebral form of ALD, a progressive neurological disorder that can cause severe disability and is often fatal if not treated early. The accumulation of VLCFAs leads to the destruction of myelin in the brain, which can result in learning disabilities, difficulty walking, and seizures.
A female fetus who inherits the gene mutation will be a carrier and will not develop the devastating childhood cerebral form of ALD. However, being a carrier is not without its own health considerations, which often emerge later in life. While the immediate health of a female newborn is not at risk in the same way as a male’s, her status as a carrier is a permanent part of her genetic makeup.
Health Implications for the Carrier Mother
For women who carry the ABCD1 gene mutation, pregnancy focuses attention on their own health. Many female carriers do not show any symptoms for decades, but a high percentage eventually develop a neurological condition known as Adrenomyeloneuropathy (AMN). Over 80% of female carriers will develop symptoms of AMN after the age of 60.
The symptoms of AMN in female carriers involve the spinal cord and peripheral nerves. This can lead to progressive stiffness and weakness in the legs, problems with balance, and changes in bladder and bowel function. Unlike the cerebral form seen in boys, AMN in women progresses more slowly, and adrenal gland dysfunction is very rare.
Pregnancy itself is not known to accelerate the onset of AMN. The physical demands of carrying a child, however, can amplify or be confused with early neurological symptoms. For instance, fatigue, back pain, and changes in gait are common in later pregnancy and can overlap with the initial signs of AMN. It is beneficial for carrier mothers to maintain a relationship with a neurologist to monitor their own health, separate from their obstetric care.
Diagnostic and Screening Options
For a known carrier mother, prenatal diagnostic procedures can determine if the fetus has inherited the ALD gene. Two primary procedures are chorionic villus sampling (CVS) and amniocentesis. CVS is performed earlier in pregnancy, between 10 and 13 weeks, and involves taking a small sample of tissue from the placenta. Amniocentesis is done between 15 and 20 weeks and involves collecting a sample of the amniotic fluid that surrounds the fetus.
Following birth, newborn screening for ALD is now widely available. In the United States, ALD is included on the Recommended Uniform Screening Panel (RUSP), meaning most newborns are screened for the condition. This screening is done through a simple heel prick blood test within the first few days of life that measures the levels of very-long-chain fatty acids.
The purpose of this comprehensive screening is early identification, which allows for proactive management. For boys diagnosed with ALD through newborn screening, regular monitoring can detect the earliest signs of cerebral ALD. This early detection opens the door for treatments, such as stem cell transplantation, which can halt the progression of the disease and significantly improve long-term outcomes.