Women with ALD can experience mild to severe symptoms. Symptoms vary in women, but many times include bowel and bladder dysfunction, pain in the extremities, and walking difficulties. Cerebral disease and adrenal insufficiency are rare in women with ALD. Until recently, women with ALD were recognized as “carriers”, who did not show symptoms of ALD. We recognize now that it is important to acknowledge that women can be symptomatic. This results in better medical care for women.
Symptomatic Women
Diagnosis
Many women are not diagnosed until a family member is diagnosed with ALD. Mothers of babies identified by newborn screening do not usually know they have ALD until they find out that their baby does. Diagnosis is commonly done with a blood test to identify above average levels of very long chain fatty acids (VLCFAs) with the caveat that up to 20% of women with the ALD gene mutation will have average VLCFA levels , which may result in a “false negative.” The most accurate means of diagnosis for a woman is through genetic testing to determine mutations in the ABCD1 gene. The earlier women are diagnosed with ALD, the easier it is to begin symptom management.
Symptoms
Even though ALD is X-linked, previous research revealed that up to 80% of heterozygous women develop symptoms during their lifetime. Symptoms may include some, all, or none of the following: muscle weakness, spasticity, bowel and bladder dysfunction, numbness, tingling, pain, gait issues, deterioration of fine motor control. Symptom management can include medications to improve spasticity issues and bowel and bladder dysfunction. Physical and occupational therapy has also proven to aid in retaining fine motor skills as well as assisting with gait. Regular physicals and consultations with urologists, physical therapists, and neurologists are very important for symptom management.
Natalie Grant, Clinical Research Coordinator, at Massachusetts General Hospital presented, “Neurological Disease Burden in Females with X-Linked Adrenoleukodystrophy” at the 2022 American Academy of Neurology meeting. Dr. Florian Eichler’s team found that, “Despite a later onset of symptoms than in males, most females with ALD develop neurological deficits in adulthood severe enough to have a negative functional impact. Click on the poster below.
Standard of Care
At this time, we are not aware of any published standards of care or clinical trials for women with ALD. With new research and increased focus on female symptoms, this will change.
These notes from our Symptomatic Women’s Call with Dr. Ali Fatemi 4.26.2021 might be helpful.
Click here to read the International Recommendations for the Diagnosis and Management of Patients with Adrenoleukodystrophy.
Click here to learn about Dr. Wolfgang Köhler’s Quality of Life in Women With X-linked Adrenoleukodystrophy clinical trial.
Click here to read Dr. Florian Eichler and Dr. John Winkelman’s publication about Restless Legs Syndrome in X-linked adrenoleukodystrophy.
Click here to read Dr. Florian Eichler and Camille Corre’s publication Beyond gait and balance: urinary and bowel dysfunction in X-linked adrenoleukodystrophy.
Clinical Trials
ALD Connect receives many questions about clinical trials for symptomatic women.
The National Institutes of Health (NIH) offers many helpful educational and informational resources about clinical trials.
There are currently some clinical trials that are recruiting patients or plan to do so soon. We have provided some basic information below. You can visit our Clinical Trials page or reach out directly to the organizations to learn more. We also recommend reaching out to your treating physician.
ACTIVE, RECRUITING: FEMALE ALD
Dr. Florian Eichler’s team at Massachusetts General Hospital is conducting a research study to learn more about how X-linked adrenoleukodystrophy (ALD) affects females.
ACTIVE, NOT RECRUITING: SMART-ALD – A New Lifestyle Intervention to Improve Quality of Life in Women With X-linked Adrenoleukodystrophy (X-ALD)
The aim of this study is to evaluate the effectiveness of a multi-approach intervention (“SMART-ALD”) on physical and mental well-being and quality of life in n=30 X-ALD symptomatic heterozygous females compared to a waiting list control group (n=30) using electronic health (ehealth) technology.
ClinicalTrials.gov: NCT04687007
RECRUITING: Quality of Life in Women With X-linked Adrenoleukodystrophy
The primary objectives of this study are 1) to assess the prevalence of symptomatic courses in females with X-ALD and 2) to determine the impact of AMN symptoms on the quality of life of affected women in various areas (including everyday life, work, social network, sleep quality, sexuality, mood).
ClinicalTrials.gov: NCT04675749
ACTIVE, NOT RECRUITING: Communication and testing experiences of adolescent girls and adult women in families with X-linked adrenoleukodystrophy
Purpose of Research: Genetic counselors are often involved in facilitating genetic testing for both a patient and their biological relatives. While testing in some circumstances is considered routine and consistent with the standard of care in the field, other circumstances involve more morally ambiguous circumstances with limited guidance and unclear standards within the genetic counseling profession. One such circumstance involves genetic testing for minors (children and adolescents). This study seeks to study the experience of girls and adolescents in families with X-ALD to better inform medical care and support needs for people and families with X-ALD in the future.
The survey is here: https://umn.qualtrics.com/jfe/form/SV_1MtlWxvkNowEYpU
RECRUITING: Treating Leg Symptoms in Women With X-linked Adrenoleukodystrophy
The investigators recently observed that up to 25% of women with X-linked adrenoleukodystrophy (ALD) have moderate to severe Restless Leg Syndrome (RLS). In this study, the investigators aim to estimate the prevalence of RLS among women with ALD and to assess whether pramipexole improves RLS symptoms as well as sleep and gait measures in women with ALD.
ClinicalTrials.gov: NCT05003648
Resources
ALD Connect hosts a Community Call for Symptomatic Women each month. This call is usually on the fourth Monday of each month at 7 PM Eastern. Be sure to follow us on social media and subscribe to our newsletter to watch for the announcements. You can also bookmark our Community Calendar, which is where we post the links to register for the Community Calls.
On August 7, 2021, ALD Connect hosted a Bootcamp for Symptomatic Women with ALD. The recordings are below.
Overview of Symptoms in Women with ALD
Dr. Florian Eichler
Moderator: Kathleen O’Sullivan-Fortin
Symptom Management
Dr. Pablo Gomery
Camille Corre
Dr. Melissa Trovato
Moderator: Kathleen O’Sullivan-Fortin
Coping with Your ALD Diagnosis
Dr. Deborah Renaud
Julie Chu
JoAnn Locy
Moderator: Jesse Torrey
Looking Ahead: Future Studies
Dr. Wolfgang Koehler
Dr. Lisa Schaefer
Jamison Seabury
Moderator: Kathleen O’Sullivan-Fortin
Terminology
Due to women receiving more attention as ALD patients and not only “carriers” of ALD, discussion on an appropriate term for women has been prominent. Many physicians who are not experts in ALD still do not consider women to have clinical symptoms of ALD, so education for providers is extremely important. Many patients also do not know how to refer to themselves. Some say women with ALD, others say women with AMN, and some want a new name for females all together. At ALD Connect, we refer to female patients as “(a)symptomatic women with ALD” to most accurately represent the manifestation of the disease in women. Please find answers to some of your frequently asked questions below.
What IS the right thing to say?
Dr. Stephan Kemp, ALD Connect Board Member and Associate Professor at UMC-Amsterdam explains, “AMN means adrenomyeloneuropathy, which is the combination of adrenal insufficiency (adreno) and spinal cord disease (myeloneuropathy). As women do not develop adrenal disease, AMN cannot be the correct name. Women either are affected with ALD or myelopathy. But since myelopathy is a difficult word and not specific to ALD alone “(a)symptomatic women with ALD” is the correct term.” ALD is the name of the entire phenotypic spectrum. From a presymptomatic newborn identified in NBS with elevated C26:0-LPC and a confirmed pathogenic mutation to cerebral ALD, isolated adrenal disease, myelopathy, and all the possible combinations. Over the years we have come to realize that trying to generate a table with specific subtypes and phenotypes and then percentages isn’t very helpful as the disease may change over time and patients would move from one grid in the table to another.
Click here to read Dr. Stephan Kemp and Dr. Marc Engelen’s paper, “Adrenoeleukodystrophy – neuroendocrine pathogenesis and redefinition of natural history”.
Why can’t we have a new name for females in our disease community?
Recent discussion with patients, doctors, and researchers about the need for a separate name for women has been very helpful in understanding the thoughts and feelings of our patients. We are already a rare disease group and by creating a NEW name for females, it breaks that rare disease group down even more, making something that is already rare, even rarer.
Why do some doctors say women with AMN?
Because women have only recently been recognized as symptomatic patients and not just carriers of ALD, information and research are constantly evolving. Women with AMN was originally thought to be an accurate term, but with new research identifying symptoms for females with ALD and lack of adrenal insufficiency, the umbrella term of ALD is much more accurate.
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