ALD Genetics and Inheritance: Understanding ABCD1

What does ABCD1 have to do with ALD?

Adrenoleukodystrophy, or ALD, is caused by disease-causing changes in the ABCD1 gene. The gene helps cells process certain fats called very long-chain fatty acids (VLCFAs). It sits on the X chromosome, which is why you may hear ALD called X-linked ALD.

A variant is a change in DNA. Finding a variant in ABCD1 is not automatically the same as finding a disease-causing variant. The laboratory’s interpretation matters.

Genetic tests examine DNA. Biochemical blood tests look at markers such as VLCFAs. These are different pieces of information that specialists interpret together. If this started with a newborn screening result, our newborn screening guide explains the follow-up process.

Sources: MedlinePlus: ALD and ABCD1 · International recommendations: diagnosis.

What should I look for on the report?

Keep a copy of the full report, including the exact variant spelling, the laboratory name, and the date. Ask the team to walk through the result and the test’s limitations with you.

Pathogenic or likely pathogenic

The laboratory has classified the variant as disease-causing or likely disease-causing. “Likely” describes evidence about the variant; it does not mean a child is likely to develop cerebral ALD at a particular age.

Variant of uncertain significance (VUS)

The evidence is not sufficient or clear enough to classify the variant as disease-causing or benign. A VUS alone neither confirms nor rules out ALD. It should not be assumed harmless.

Benign or likely benign

The variant is classified as not disease-causing or likely not disease-causing. Ask how the full result fits the reason for testing and whether anything remains unexplained.

A negative result also needs context: what did the test examine, and what can it miss? Ask whether the findings answer the original question or whether further evaluation is needed.

For more on uncertain findings, see the ALD Grey Zone and ABCD1 VUS guide.

Sources: MedlinePlus: interpreting genetic results · International ALD recommendations.

How is an ABCD1 variant passed down?

These examples describe the usual X-linked inheritance pattern, using a known disease-causing variant. Your genetics team can explain the pattern in your family.

A mother with the variant on one of her two X chromosomes

Each child has a 50% chance of inheriting that variant in each pregnancy. This applies to sons and daughters. Each pregnancy is independent; one child’s result does not change the next child’s chance.

A father whose X chromosome carries the variant

He passes his X chromosome and the variant to all of his daughters. Sons receive his Y chromosome, so they do not inherit the variant from him.

These are chances of inheriting the variant, not chances of developing cerebral ALD or a particular level of symptoms. A 50% chance also does not mean that exactly half of someone’s children will inherit it.

A VUS can be inherited, too. Knowing that it was passed through a family does not, by itself, establish what it means medically.

Sources: MedlinePlus: ALD inheritance · MedlinePlus: inheritance and each pregnancy · International recommendations: uncertain variants.

What if nobody else in the family has ALD?

A family may have no recognized history of ALD when a result is found. Some relatives may have no symptoms or may not have been diagnosed. Sometimes a disease-causing variant is new in the family; the term for this is de novo.

If a child’s variant is not found in a parent’s blood sample, that does not always make the chance of it happening again zero. For example, a variant can be present in some egg-producing cells without appearing in the mother’s blood test. This is called germline mosaicism. A genetic counselor can explain whether this matters to your situation.

None of this is anyone’s fault. Testing is a way to understand the finding and plan care.

Source: GeneReviews: X-linked adrenoleukodystrophy, genetic counseling.

Women’s health is part of the picture

Women with ALD can develop spinal cord and nerve symptoms, often in adulthood. Describing someone only as an “unaffected carrier” can overlook her own health needs.

A normal VLCFA blood result does not reliably exclude ALD in women. Genetic evaluation can be especially helpful, and care recommendations differ from those for boys and men. Ask what the result means for the woman or girl herself, as well as for her relatives.

Our dedicated women with ALD guide covers symptoms, follow-up, and support in more detail.

Source: International ALD recommendations: women, testing, and care.

Who else in the family might benefit from testing?

Start with the actual report and a genetic counselor. They can help map the family history and explain which relatives may benefit from evaluation. Testing relatives after a finding in one person is sometimes called cascade testing.

When a disease-causing family variant is known, testing can look specifically for that variant. Identifying ALD in a boy before symptoms can allow timely adrenal and brain monitoring.

If the result is uncertain

Testing selected relatives may help specialists gather evidence about a VUS. That is different from testing for a confirmed disease-causing family variant. Family results do not automatically settle a VUS, and the purpose and possible outcomes of testing should be discussed first.

If the person being tested is a child

Ask how a result could change care during childhood, why testing is being suggested now, and how the child can be included in an age-appropriate way. The conversation should address that child’s circumstances and the family’s questions.

Sources: GeneReviews: evaluation of relatives at risk · International recommendations: family screening and diagnosis.

Can the interpretation change?

New evidence can sometimes change a variant’s classification. Ask who will request an updated interpretation, whether the laboratory has a reanalysis or notification process, and how to keep contact information current. Do not assume an update will arrive automatically.

An updated classification and a person’s health over time are still different questions. Discuss any new information with the care team before changing a monitoring plan.

Sources: MedlinePlus: uncertain results and additional evidence · International ALD recommendations.

Family planning, if you want that conversation

You can ask about reproductive options without having made a decision about having children. Counseling should help you understand choices in the context of your own priorities.

When a family’s disease-causing variant is known, options may include prenatal diagnostic testing or IVF with preimplantation genetic testing for a monogenic condition, called PGT-M. A VUS needs a separate specialist and laboratory discussion; do not assume the same testing options apply.

Testing for a variant cannot predict how severe ALD would be for an individual. Ask about accuracy, limitations, and confirmatory testing. PGT-M does not guarantee a pregnancy or a child without other health conditions.

Sources: GeneReviews: family planning · ACOG: preimplantation genetic testing.

Questions to bring to a genetic counselor

Bring the full genetic report, relevant blood-test results, and the questions you most want answered. You can start with these:

• What exact variant and classification does our report show?
• Does this establish ALD, or is more evidence needed?
• What can this result tell us, and what can it not predict?
• Which relatives may benefit from testing, and why?
• Is a child’s testing meant to guide care or help investigate a VUS?
• What follow-up applies to each person who has this finding?
• Who will review new evidence or request a fresh interpretation?
• If we want reproductive counseling, what options fit our situation?

A few terms you may hear

X-linked

Describes a gene located on the X chromosome and its inheritance pattern. It does not mean only boys or men can be affected.

Variant classification

An assessment of evidence about whether a genetic change causes disease.

Prognosis

The expected course of a person’s health or condition over time.

Targeted family testing

Testing that looks for a particular variant already identified in a relative.

Genetic counseling

A conversation about genetic findings, their meaning for a person and family, and choices about testing and care.

Sources and further reading

Sources checked November 8, 2026. Medical expert review is still pending.

• GeneReviews: X-linked adrenoleukodystrophy · Genetic counseling, relatives’ testing, and family planning; updated April 6, 2023.
• MedlinePlus Genetics: X-linked adrenoleukodystrophy · ABCD1 and inheritance; updated October 26, 2022.
• MedlinePlus: interpreting genetic test results · Result categories and uncertainty; updated July 28, 2021.
• MedlinePlus: understanding inheritance chances · X-linked patterns and independent pregnancies.
• Engelen and colleagues: international ALD recommendations · Neurology, 2022; diagnosis, women’s health, and family screening.
• ACOG: preimplantation genetic testing · Committee Opinion 799, 2020; uses and limitations of testing.