Symptoms may include some, all, or none of the following:

• Ataxia: loss of the ability to coordinate muscle movement
• Falling or tripping
• Fatigue and sleep disturbances
• Hypertonia: excessive muscle tone
• Peripheral neuropathy: pain, numbness, or tingling in the legs or feet
• Sexual dysfunction
• Spastic paraparesis: gradual, progressive weakness and stiffness of the legs
• Urinary disturbances or incontinence and bowel urgency or incontinence
• Walking and balance problems: general leg weakness and stiffness as well as decreased balance that can progress to difficulty walking or an unusual gait (mobility devices such as canes, walkers, and wheelchairs may be needed over time)

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.

Currently, there is no cure available for symptomatic women with ALD. Current treatments aim to alleviate some of the symptoms of the disease. Symptom management can include medications to improve spasticity issues and bowel and bladder dysfunction. Many patients also undergo regular physical and/or occupational therapy. Work with your care team to find a treatment plan that works for you. Because cerebral ALD and adrenal insufficiency are extremely rare in women with ALD, current standards of care do not recommend routine monitoring for these manifestations in girls or women with ALD. Regular physicals and consultations with urologists, physical therapists, and neurologists are very important for symptom management. Current standards of care recommend yearly exams to follow-up on myelopathy symptoms in symptomatic woman with ALD.

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

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

These notes from our Symptomatic Women’s Call with Dr. Amena Smith Fine on 5.20.2024 might be helpful.

These notes from our Symptomatic Women’s Call with Dr. Ali Fatemi on 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.

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. ALD Connect also hosts a peer mentor program, which connects less experienced community members to more experienced members of a similar phenotypes. You can apply for a peer mentor here.

On July 22, 2022, ALD Connect hosted an Externally-Led Patient-Focused Drug Development Meeting to educate the FDA on adult manifestations of ALD, including symptomatic women with ALD. View the recording and our resulting Voice of the Patient Report here. 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

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, “Adrenoleukodystrophy – neuroendocrine pathogenesis and redefinition of natural history”.

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.

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 more accurate.