Materiały źródłowe

• #1 X-linked adrenoleukodystrophy: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/x-linked-adrenoleukodystrophy/

  X-linked adrenoleukodystrophy is a genetic disorder that mainly affects the nervous system and the adrenal glands, which are located on top of each kidney. […] The rate at which this disorder progresses is variable but can be extremely rapid, often leading to total disability within a few years. The life expectancy of individuals with this type depends on whether early diagnosis and treatment are available. Without treatment, individuals with the cerebral form of X-linked adrenoleukodystrophy usually survive only a few years after symptoms begin. […] The life expectancy of individuals with the adrenal insufficiency form depends on the severity of the signs and symptoms, but typically this is the mildest of the three types. […] Rarely, individuals with X-linked adrenoleukodystrophy develop multiple features of the disorder in adolescence or early adulthood. In addition to adrenocortical insufficiency, these individuals usually have psychiatric disorders and a loss of intellectual function (dementia). It is unclear whether these individuals have a distinct form of the condition or a variation of one of the previously described types.

• #1 Adrenoleukodystrophy – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562328/

  The prognosis for neonatal adrenoleukodystrophy and most forms of X-ALD is generally poor. […] However, patients with adrenomyeloneuropathy can survive past age 65, although often with significant morbidity. […] Treatment is usually limited to symptomatic supportive management. […] Replacement therapy is effective for patients with Addison disease, while HSCT may benefit asymptomatic patients identified through newborn screening or incidental imaging, as well as those with mild symptoms.

• #2 Adrenoleukodystrophy – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562328/

  The prognosis for neonatal adrenoleukodystrophy and most forms of X-ALD is generally poor. […] However, patients with adrenomyeloneuropathy can survive past age 65, although often with significant morbidity. […] Treatment is usually limited to symptomatic supportive management. […] Replacement therapy is effective for patients with Addison disease, while HSCT may benefit asymptomatic patients identified through newborn screening or incidental imaging, as well as those with mild symptoms.

• #3 Adrenoleukodystrophy (ALD): Causes, Types, Symptoms, Prognosis

  https://www.webmd.com/brain/what-is-adrenoleukodystrophy

  Prognosis for ALD: More research is being done on how to prevent and treat ALD, but the outlook for people who have it is still poor. Death often occurs within 1 to 10 years of having first symptoms. The earlier ALD can be diagnosed, the better. Experts believe that all treatments work best when given before symptoms start or soon after. […] Life expectancy for ALD depends on the severity of symptoms and the type you have. The form of ALD with the poorest prognosis is cerebral ALD (CALD), for which symptoms begin to appear around the ages of 4 to 10 and progress rapidly. Adult onset symptoms of ALD are milder than those of CALD, with 28 being the average age at which symptoms start to appear. Patients with ALD who don’t have brain involvement (the disease hasn’t affected their brain) have a better prognosis than those who do. […] Adrenoleukodystrophy has no cure, but there are promising treatments involving gene therapy and stem cell therapy that slow the progression of the disease if symptoms are caught early.

• #4 X-linked adrenoleukodystrophy (X-ALD): clinical presentation and guidelines for diagnosis, follow-up and management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3503704/

  It is debatable whether men with X-ALD can remain really asymptomatic for life. […] The severity and progression cannot be predicted for individual patients. […] Not every boy or man with X-ALD will develop cerebral ALD. About 35-40% of boys with an ABCD1 mutation will develop CCALD before reaching adulthood. […] However, it is now well established that at least 20% of adult males with the AMN phenotype will develop cerebral demyelination later in life. […] If this occurs, these patients have the same poor prognosis as boys with inflammatory cerebral ALD. […] It is well documented that women develop symptoms that resemble AMN, but there is no prospective study with adequate numbers to really estimate what percentage of women become symptomatic. […] For the majority of patients with X-ALD there is currently no curative or preventive treatment. […] The eventual phenotype of X-ALD in an individual will most likely be determined by the combination of several epigenetic and environmental modifiers, most of which have not been identified.

• #5 X-linked adrenoleukodystrophy (X-ALD): clinical presentation and guidelines for diagnosis, follow-up and management | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-7-51

  Not every boy or man with X-ALD will develop cerebral ALD. About 35-40% of boys with an ABCD1 mutation will develop CCALD before reaching adulthood. It can still not be predicted who will develop this devastating manifestation of the disease. Previously it was believed that after reaching adulthood this complication was very rare. However, it is now well established that at least 20% of adult males with the AMN phenotype will develop cerebral demyelination later in life. If this occurs, these patients have the same poor prognosis as boys with inflammatory cerebral ALD. […] It is well documented that women develop symptoms that resemble AMN, but there is no prospective study with adequate numbers to really estimate what percentage of women become symptomatic. We recently completed a large prospective cohort study to describe the symptomatology of X-ALD in women.

• #6 SciELO Brazil – X-LINKED ADRENOLEUKODYSTROPHY IN BRAZIL: A CASE SERIES X-LINKED ADRENOLEUKODYSTROPHY IN BRAZIL: A CASE SERIES

  https://www.scielo.br/j/rpp/a/NNRFHCLpSvmDLVjG9FhRxGt/

  All phenotypes of X-linked adrenoleukodystrophy, except for myelopathy in women, were presented in the studied population, which mainly consisted of children and adolescents. […] Most of the patients with cerebral demyelinating inflammatory adrenoleukodystrophy were not diagnosed in time for hematopoietic stem cell transplantation. […] The mean delay between the onset of symptoms and the diagnosis of CALD was 11 months. […] The timing between first manifestations and diagnosis of CALD in our study should have been much faster, according to the literature, since there may be total disability within six to 24 months of disease progression, preventing HSCT and consequently the interruption of the inflammatory demyelination.

• #7 ALD: Adrenoleukodystrophy, Disease, X-Linked

  https://my.clevelandclinic.org/health/diseases/6030-adrenoleukodystrophy-ald

  The prognosis for people with ALD depends on the type. Children with childhood cerebral X-ALD generally have a poor prognosis. Unless they receive a stem cell transplant early in the disease, their neurological function deteriorates. In many cases, children pass away within a few years after symptoms begin. […] For people with adult-onset AMN, the disease can progress over many decades.

• #8 X-linked adrenoleukodystrophy (X-ALD): clinical presentation and guidelines for diagnosis, follow-up and management | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-7-51

  It is debatable whether men with X-ALD can remain really asymptomatic for life. It seems probable that there is only presymptomatic X-ALD in men. Although there is no large prospective cohort study to accurately determine the natural history of the disease, several general observations can be made. It is likely that all patients with X-ALD if they survive into adulthood eventually develop myelopathy, i.e. AMN. Usually, symptoms and signs occur from the 3rd decade of life, but much earlier, or much later, is possible. The severity and progression cannot be predicted for individual patients. There is marked variability ranging from men with X-ALD that are wheelchair bound by the age of 25 and others who are able to walk with a cane while in their seventies. This is important when counseling patients: symptoms will occur, but only time will tell how severely affected an individual will be.

• #9 Disease progression in women with X-linked adrenoleukodystrophy is slow | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-019-1008-6

  Progression of spinal cord disease can be detected with EDSS, but not with ALDS or SF-36 after a follow-up period of almost 8 years. […] Moreover, age and the duration of symptoms seem positively associated with the rate of progression. […] Although a significant progression was measurable, it was below the rate generally conceived as clinically relevant. […] These results have implications for counseling women with ALD. These women may be informed that progression is usually very slow, with significant change occurring over years or decades, although in individual patients onset may be early and the disease more progressive. […] Progression seems so slow that it cannot be detected by current outcome measures such as EDSS, ALDS and SF-36 unless a study lasts for at least 8 years, which is typically not feasible from a financial perspective.

• #10 X-linked adrenoleukodystrophy (X-ALD): clinical presentation and guidelines for diagnosis, follow-up and management | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-7-51

  For the majority of patients with X-ALD there is currently no curative or preventive treatment. However, several promising new approaches will hopefully come to fruition in the future. […] The eventual phenotype of X-ALD in an individual will most likely be determined by the combination of several epigenetic and environmental modifiers, most of which have not been identified. Much research is currently focused on identifying these modifiers to better predict clinical outcome in individual patients.

• #11 Lipidomic biomarkers in plasma correlate with disease severity in adrenoleukodystrophy | Communications Medicine

  https://www.nature.com/articles/s43856-024-00605-9

  This study reveals the profound impact of ALD on the lipidome and provides potential biomarkers for predicting clinical outcomes in ALD patients. […] Our results show a strong association between higher levels of VLCFA-containing lipids and the presence of cerebral ALD, adrenal insufficiency, and severe spinal cord disease in male ALD patients. […] In female ALD patients, VLCFA-lipid levels correlate with X-inactivation patterns, and higher levels are associated with more severe disease manifestations. […] Overall, this study provides robust evidence of a strong association between plasma VLCFA-lipid levels and disease severity in both male and female ALD patients.

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