Adrenoleukodystrofia – Epidemiologia

Adrenoleukodystrofia
Epidemiologia

Adrenoleukodystrofia (ALD) jest najczęstszym zaburzeniem peroksysomalnym o częstości występowania szacowanej na 1:14 000-17 000 żywych urodzeń, z wyższą częstością u noworodków płci męskiej (około 1:21 000). Choroba ma sprzężony z chromosomem X charakter dziedziczenia, co powoduje pełnoobjawowy przebieg u mężczyzn, podczas gdy kobiety są zazwyczaj nosicielkami z łagodniejszymi objawami. Niewydolność nadnerczy dotyczy 80-86% mężczyzn z ALD, najczęściej między 3 a 10 rokiem życia, a wczesne wykrycie zmian demielinizacyjnych w mózgu za pomocą MRI jest kluczowe dla wdrożenia leczenia, w tym allogenicznego przeszczepu krwiotwórczych komórek macierzystych (HSCT). Zalecane jest regularne monitorowanie poziomów ACTH i kortyzolu co 3-4 miesiące w pierwszych 2 latach życia oraz MRI mózgu od 12-18 miesiąca życia z częstotliwością dostosowaną do wieku i obecności zmian.

Epidemiologia Adrenoleukodystrofii

leukodystrofia/” title=”adrenoleukodystrofia” class=”to-tag” data-termid=”64480″>Adrenoleukodystrofia (ALD) jest najczęstszym zaburzeniem peroksysomalnym występującym na świecie. Według różnych źródeł, częstość występowania ALD szacuje się na około 1 na 14 000-17 000 żywych urodzeń (uwzględniając zarówno mężczyzn, jak i kobiety)¹²³. Niektóre badania podają szerszy zakres występowania – od 1 na 20 000 do 1 na 50 000 osób⁴⁵. W przypadku noworodków płci męskiej częstość występowania wynosi około 1 na 21 000⁶. Noworodkowa postać adrenoleukodystrofii występuje rzadziej – z częstością około 1 na 50 000¹.

Warto zaznaczyć, że dane dotyczące częstości występowania ALD mogą ulec zmianie w wyniku wprowadzenia badań przesiewowych noworodków, które umożliwiają wczesne wykrycie choroby. Na przykład, badanie przeprowadzone w stanie Minnesota w USA wykazało znacznie wyższą częstość występowania ALD niż wcześniej raportowano – 1 na 4845 u dziewczynek i 1 na 3878 u chłopców⁷. Z kolei w Kalifornii po wprowadzeniu badań przesiewowych odnotowano częstość 1 na 14 397 u chłopców i 1 na 9593 u dziewczynek⁷.

Występowanie geograficzne i etniczne

Adrenoleukodystrofia występuje na całym świecie i dotyka wszystkich grup etnicznych bez wyraźnej predylekcji rasowej¹⁶. Choroba została zdiagnozowana we wszystkich krajach europejskich i latynoamerykańskich, a także w Chinach, Japonii, Indiach, Izraelu, Arabii Saudyjskiej oraz wśród różnych grup etnicznych, w tym Afroamerykanów, rdzennych Amerykanów i Maorysów⁸.

Chociaż choroba nie wykazuje predylekcji do konkretnych grup etnicznych, niektóre badania sugerują wyższą częstość występowania wariantów patogennych genu ABCD1 u osób pochodzenia latynoskiego i afrykańskiego⁷⁹. Jednocześnie zaobserwowano wyższy wskaźnik diagnostyczny wśród osób pochodzenia kaukaskiego, co może sugerować potencjalną stronniczość rasową w diagnozowaniu choroby przed wprowadzeniem badań przesiewowych noworodków⁷.

W Japonii częstość występowania ALD szacuje się na poziomie 1 na 30 000 do 1 na 50 000 chłopców, co jest zbliżone do danych z innych krajów¹⁰. We Francji szacuje się, że częstość występowania ALD wynosi około 1 na 17 000 urodzeń, z czego 35-40% może rozwinąć dziecięcą mózgową postać ALD (CCALD), co prowadzi do oczekiwanej rocznej zachorowalności na poziomie 5-6 chłopców w tym kraju¹¹.

Rozkład płciowy

Adrenoleukodystrofia sprzężona z chromosomem X (X-ALD) występuje znacznie częściej u mężczyzn niż u kobiet ze względu na dziedziczenie recesywne sprzężone z chromosomem X¹⁶. Mężczyźni z jedną zmutowaną kopią genu ABCD1 rozwijają pełnoobjawową chorobę, podczas gdy kobiety są zazwyczaj nosicielkami i mogą wykazywać łagodniejsze objawy lub pozostawać bezobjawowe¹².

Około 80% kobiet z genem ALD rozwinie pewne objawy adrenomieloneuropatii (AMN) w ciągu życia, zazwyczaj w późniejszym wieku niż mężczyźni i z wolniejszą progresją¹³. U kobiet rozwój mózgowej leukodystrofii lub niewydolności nadnerczy jest niezwykle rzadki i został opisany jedynie w pojedynczych przypadkach¹³.

Według danych z 2023 roku, około 60% przypadków ALD diagnozowano u mężczyzn w oparciu o płciowo-specyficzną częstość występowania choroby w siedmiu głównych rynkach medycznych (7MM: USA, Niemcy, Hiszpania, Włochy, Francja, Wielka Brytania i Japonia)¹⁴.

Nadzór i monitorowanie choroby

Wczesna diagnoza i systematyczne monitorowanie są kluczowe w leczeniu adrenoleukodystrofii, szczególnie w przypadku pacjentów bezobjawowych zidentyfikowanych poprzez badania przesiewowe noworodków lub badania rodzinne²¹⁵.

Badania przesiewowe noworodków

Badania przesiewowe noworodków w kierunku ALD zostały wprowadzone w wielu krajach, co pozwala na wczesne wykrycie choroby i wdrożenie odpowiedniego monitorowania oraz interwencji terapeutycznych³⁷. Stan Nowy Jork jako pierwszy w Stanach Zjednoczonych wprowadził badania przesiewowe noworodków w kierunku ALD w 2013 roku, po uchwaleniu tzw. Aidens Law¹⁶¹⁷.

W 2016 roku ALD została dodana do Recommended Uniform Screening Panel (RUSP) w Stanach Zjednoczonych, co stanowi listę zaburzeń zalecanych do badań przesiewowych noworodków przez Departament Zdrowia i Opieki Społecznej¹⁷¹⁸. Obecnie badania przesiewowe w kierunku ALD są prowadzone w 44 stanach USA, na Tajwanie oraz w Holandii, a w Japonii, Włoszech i Chinach prowadzone są badania pilotażowe¹⁶.

Protokoły badań przesiewowych różnią się między poszczególnymi ośrodkami, ale wszystkie obejmują pomiar bardzo długołańcuchowych kwasów tłuszczowych (VLCFA) z próbki krwi oraz badania potwierdzające⁷. Po potwierdzeniu rozpoznania ALD, pacjenci kierowani są na konsultacje genetyczne oraz do ośrodków specjalistycznych w celu dalszego monitorowania i leczenia⁷.

Monitorowanie niewydolności nadnerczy

Niewydolność nadnerczy występuje u około 80-86% mężczyzn z ALD, z najwyższym poziomem zachorowań między 3 a 10 rokiem życia⁷¹⁹. Chociaż VLCFA zaczynają kumulować się już w okresie płodowym, nie odnotowano przypadków niewydolności nadnerczy przy urodzeniu. Najwcześniejsze biochemiczne oznaki niewydolności nadnerczy zaobserwowano u pacjentów w wieku 5 tygodni i 3,5 miesiąca⁷.

Eksperci zalecają regularne badania przesiewowe w kierunku niewydolności nadnerczy u wszystkich pacjentów płci męskiej z rozpoznaną ALD. Rekomendowane jest badanie poziomów ACTH i kortyzolu co 3-4 miesiące w pierwszych 2 latach życia, a następnie co 4-6 miesięcy⁷¹⁹. Nie ma zaleceń dotyczących badań przesiewowych w kierunku niewydolności nadnerczy u kobiet z ALD, ponieważ częstość występowania tej komplikacji jest u nich niska⁷.

Monitorowanie rezonansu magnetycznego

Wszyscy neurologicznie bezobjawowi mężczyźni z potwierdzonym rozpoznaniem ALD powinni być poddawani regularnemu monitorowaniu za pomocą rezonansu magnetycznego (MRI) mózgu, ponieważ ponad połowa z nich ostatecznie rozwinie postępującą leukodystrofię²⁰. Wczesne wykrycie zmian w mózgu może umożliwić wdrożenie leczenia, które potencjalnie może zapobiec najpoważniejszym konsekwencjom choroby²¹.

Panel ekspertów osiągnął 95,7% konsensusu dotyczącego następujących parametrów nadzoru:

Wykonanie pierwszego MRI między 12 a 18 miesiącem życia
Wykonanie drugiego MRI rok po badaniu wyjściowym
Między 3 a 12 rokiem życia wykonywanie MRI ze wzmocnieniem kontrastowym co 6 miesięcy
Po 12 roku życia wykonywanie MRI raz w roku²²

W przypadku wykrycia zmiany demielinizacyjnej zaleca się wykonywanie MRI ze wzmocnieniem kontrastowym co 3 miesiące oraz pilne skierowanie do ośrodka transplantacyjnego, jeśli rozwijają się zmiany zapalne¹⁹. Rutynowe nadzorowanie za pomocą MRI nie jest zalecane u kobiet, ponieważ leukodystrofia występuje u nich rzadko²⁰.

Znaczenie nadzoru w adrenoleukodystrofii

Monitorowanie bezobjawowych chłopców i mężczyzn z ALD jest istotne z dwóch głównych powodów:

Wczesnego wykrycia niewydolności nadnerczy
Wczesnego wykrycia mózgowej postaci ALD za pomocą MRI, co umożliwia rozważenie allogenicznego przeszczepu krwiotwórczych komórek macierzystych (HSCT), jeśli dostępny jest zgodny dawca⁸

Noworodek płci męskiej z rozpoznaniem ALD ma 35-40% ryzyko rozwoju mózgowej postaci ALD między 3 a 18 rokiem życia, choć mózgowa postać ALD może wystąpić również w dorosłości⁸. Szacuje się, że w ciągu 10 lat około 20% pacjentów z adrenomieloneuropatią (AMN) rozwinie mózgową postać choroby²³.

Ze względu na brak biomarkerów prognostycznych, niemożliwe jest przewidzenie przebiegu choroby u poszczególnych pacjentów z ALD, co prowadzi do jednolitego, rozszerzonego monitorowania wszystkich bezobjawowych mężczyzn z tym rozpoznaniem¹⁶.

Rejestry i nadzór populacyjny

Dla lepszego zrozumienia naturalnej historii ALD oraz czynników związanych z początkiem i progresją choroby, tworzone są rejestry pacjentów na poziomie krajowym i międzynarodowym²⁴.

Krajowe i międzynarodowe rejestry

Krajowy Rejestr ALD na Uniwersytecie Minnesoty dąży do stworzenia największego na świecie zbioru informacji klinicznych, skanów MRI i próbek biologicznych związanych z ALD²⁴. Jest to prospektywny, nieterapeutyczny protokół mający na celu utworzenie i utrzymanie rejestru uczestników z ALD oraz znanych/domniemanych nosicieli ALD²⁴.

Dane epidemiologiczne dotyczące ALD są gromadzone i analizowane w siedmiu głównych rynkach medycznych (7MM): Stanach Zjednoczonych, Niemczech, Francji, Włoszech, Hiszpanii, Wielkiej Brytanii i Japonii²⁵²⁶. Według analizy, w 2017 roku całkowita liczba przypadków ALD w tych krajach wynosiła 55 242²⁶.

Wśród pięciu krajów europejskich, Niemcy miały najwyższą zdiagnozowaną częstość występowania ALD z 1895 przypadkami, następnie Francja i Wielka Brytania. Włochy miały najniższą zdiagnozowaną częstość występowania – 1126 przypadków w 2017 roku²⁶.

Badania populacyjne i ekonomiczne

We Francji przeprowadzono pierwsze badanie oceniające bezpośrednio wykorzystanie zasobów opieki zdrowotnej i związane z tym koszty leczenia CCALD na podstawie danych z rzeczywistej praktyki klinicznej¹¹. Badanie to oszacowało liczbę pacjentów z CCALD we Francji, ich charakterystykę kliniczną, postępowanie terapeutyczne oraz ewolucję średnio- i długoterminową, poprzez analizę 6-letniego okresu obserwacji¹¹.

Przy analizie ewolucji kosztów w czasie i progresji choroby, zaobserwowano dwa zupełnie różne wzorce między pacjentami poddanymi HSCT a tymi bez HSCT¹¹. HSCT w leczeniu CCALD okazał się kluczowy, gdy wykonywany był wystarczająco wcześnie, aby zapobiec objawom i ciężkim deficytom motorycznym¹¹.

Według danych DelveInsight, rynek ALD w siedmiu głównych rynkach medycznych ma doświadczyć znaczących zmian w okresie 2020-2034²⁷. W 2023 roku Stany Zjednoczone odpowiadały za największy rozmiar rynku ALD (około 400 milionów USD) w porównaniu do EU4 (Niemcy, Hiszpania, Włochy, Francja), Wielkiej Brytanii i Japonii¹⁴.

Wyzwania i perspektywy w nadzorze nad adrenoleukodystrofią

Pomimo postępów w diagnozowaniu i monitorowaniu ALD, istnieje wiele wyzwań i obszarów wymagających dalszego rozwoju¹.

Wyzwania w diagnozowaniu i monitorowaniu

Jednym z głównych wyzwań w diagnostyce ALD jest to, że wczesna identyfikacja choroby pozostaje trudna z powodu niespecyficznych początkowych objawów, które nakładają się na inne problemy medyczne i rozwojowe²⁸. Chociaż programy badań przesiewowych noworodków będą pomagać we wczesnej identyfikacji i nadzorze chłopców z ALD, potencjał opóźnionej diagnozy utrzymuje się tam, gdzie badania te nie są dostępne oraz gdy brak historii rodzinnej uniemożliwia badania rodzinne²⁹.

Kolejnym wyzwaniem jest brak biomarkerów prognostycznych, które pozwoliłyby przewidzieć, którzy chłopcy z ALD rozwiną mózgową postać choroby³⁰. Z tego powodu wszyscy chłopcy zdiagnozowani z ALD muszą być regularnie monitorowani za pomocą MRI³⁰.

Badanie retrospektywne bazy danych Pediatric Health Information System Stowarzyszenia Szpitali Dziecięcych w USA wykazało wyższą częstość występowania patogennych wariantów ABCD1 u osób pochodzenia latynoskiego i afrykańskiego, mimo wyższych wskaźników diagnostycznych u osób rasy kaukaskiej, co sugeruje potencjalną stronniczość rasową w diagnozowaniu przed wprowadzeniem badań przesiewowych noworodków⁷.

Perspektywy i przyszłe kierunki

Wprowadzenie badań przesiewowych noworodków w kierunku ALD stanowi znaczący postęp w walce z tą chorobą. Wczesna diagnoza umożliwia regularne monitorowanie funkcji nadnerczy i wczesne wykrycie mózgowej postaci ALD, co z kolei pozwala na wdrożenie leczenia, zanim pojawią się nieodwracalne uszkodzenia¹⁸.

Zwiększa się również świadomość, że ALD nie jest wyłącznie chorobą wieku dziecięcego. Jest to najczęstsza leukodystrofia diagnozowana w dorosłości, a rosnąca liczba dorosłych pacjentów płci męskiej i żeńskiej uzyskuje diagnozę dzięki zwiększonemu włączeniu ALD do paneli badań przesiewowych noworodków i szerszemu wykorzystaniu testów genetycznych³¹.

Potrzebne są dalsze badania w celu lepszego zrozumienia naturalnej historii choroby, w tym czynników związanych z początkiem i progresją choroby²⁴. Istotne jest również opracowanie biomarkerów, które mogłyby pomóc w przewidywaniu, którzy pacjenci są narażeni na ryzyko rozwoju mózgowej postaci ALD¹.

Konieczne jest również uwzględnienie aspektów psychologicznych diagnozy i nadzoru. Badanie jakościowe wykazało, że chociaż wczesne wykrycie i nadzór umożliwiają potencjalnie ratujące życie leczenie ALD, wiążą się one również z rozszerzonym monitorowaniem, co może mieć wpływ psychologiczny na pacjentów i ich rodziny¹⁶.

Istotne jest również rozwijanie międzynarodowej współpracy w zakresie badań i tworzenia rejestrów pacjentów, co pozwoli na lepsze zrozumienie epidemiologii ALD w różnych populacjach oraz na opracowanie bardziej skutecznych strategii diagnostycznych, monitorujących i terapeutycznych¹.

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Materiały źródłowe

#1 Adrenoleukodystrophy – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK562328/
Adrenoleukodystrophy is the most common genetic disorder affecting peroxisomes, with an estimated prevalence of 1 in 14,700. The disease incidence is higher in patients of Latino or African descent. Neonatal adrenoleukodystrophy has a prevalence of 1 in 50,000. […] Adrenoleukodystrophy affects approximately 1 in 20,000 to 1 in 50,000 individuals globally. […] Adrenoleukodystrophy primarily affects males due to its X-linked recessive inheritance. Females are typically carriers and may have mild or no symptoms. […] Adrenoleukodystrophy is found worldwide and affects all ethnic groups. Prevalence varies based on genetic factors and diagnostic capabilities. […] The primary risk factor is an inherited mutation in the ABCD1 gene. A family history of adrenoleukodystrophy also increases the risk. […] Early diagnosis through newborn screening is critical. Genetic counseling for families is essential. Increased awareness and research are needed to improve diagnostics, treatment, and support.
#2 X-Linked Adrenoleukodystrophy – GeneReviewsÂ® – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK1315/
The prevalence of X-ALD is estimated at between one in 14,000 and one in 17,000 male births. […] For boys receiving targeted therapy for neurologic disease, the treating neurologist / biochemical geneticist monitors existing manifestations, the individual’s response to targeted therapy, and need for supportive care. […] Boys at risk for cCALD who are possible candidates for targeted therapy require frequent assessments starting at age 12 months. […] It is appropriate to evaluate at-risk male relatives of an affected individual through measurement of plasma concentration of very long-chain fatty acids or molecular genetic testing if the familial ABCD1 pathogenic variant is known in order to identify as early as possible those who would benefit from screening for primary adrenocortical insufficiency and to facilitate timely identification of young males who might benefit from targeted treatment for cCALD.
#3 Orphanet: X-linked adrenoleukodystrophy
https://www.orpha.net/en/disease/detail/43
X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder with an estimated birth prevalence of 1/17,000 (male and female). It has been reported throughout the world. […] Newborn screening for X-ALD has been recently implemented in certain regions.
#4 X-linked adrenoleukodystrophy | Radiology Reference Article | Radiopaedia.org
https://radiopaedia.org/articles/x-linked-adrenoleukodystrophy-1?embed_domain=hackmd.io%2F%40yIPUAFeCSL2JsU8smR5nJQ%2Fbnjhjgjghjghjghfavicon.icoradiopaedia-icon-144.pngfavicon.icoradiopaedia-icon-144.png&lang=gb
The estimated incidence of adrenoleukodystrophy is 1:20,000-50,000. Due to its X-linked inheritance, it classically affects young males, although carrier females can be affected. […] Although most cases are diagnosed in childhood, a significant proportion of cases manifest in young adults (typically late 20s) and thus adrenoleukodystrophy is one of the most common adult-onset leukodystrophies.
#5 Prevalence – Adrenoleukodystrophy News
https://adrenoleukodystrophynews.com/prevalence/
Because the mutated gene causing the disease is on the X chromosome, men are at higher risk of developing ALD. […] ALD does not discriminate based on ethnicity and is reported in similar frequency in populations around the world. […] According to the U.S. National Library of Medicine, the prevalence of ALD is 1 in 20,000 to 50,000 individuals worldwide. […] In the U.S., 1 in every 21,000 men is thought to be affected by ALD while 1 in 16,800 women are thought to be ALD carriers. […] As per a newborn screening conducted in the state of New York, the incidence of ALD at birth was estimated to be 1 in 15,000. Among the 700,000 newborns screened in a three-year period, 45 babies were diagnosed with ALD. […] According to combined data describing the distribution of ALD types in different regions of the world, CALD is the most common, with around 33 to 57 percent of all reported cases.
#6 Adrenoleukodystrophy epidemiology and demographics – wikidoc
https://www.wikidoc.org/index.php/Adrenoleukodystrophy_epidemiology_and_demographics
Adrenoleukodystrophy is the most common peroxisomal disorder, with an estimated incidence of 1 in 17,000 births (male and female) and 1 in 21,000 males in the United States. […] The prevalence of X-linked adrenoleukodystrophy is approximately 1 in 20,000 individuals. This condition occurs with a similar frequency in all populations. […] The lifetime prevalence of adrenal insufficiency in ALD is ~80%. […] There is no racial predilection to adrenoleukodystrophy. […] Men are more commonly affected by adrenoleukodystrophy than women. However, women can be a carrier of the disease.
#7 Monitoring for and Management of Endocrine Dysfunction in Adrenoleukodystrophy
https://www.mdpi.com/2409-515X/8/1/18
The published prevalence of ALD based on newborn screening has varied but is consistent with improved identification of those with ALD. In the largest published cohort, California State reported the prevalence of ALD was 1 in 14,397 males and 1 in 9593 females with ~1.85 million newborns screened in the first four years. Minnesota, a relatively small state with potential founder effects, reported an even higher prevalence of 1:4845 in females and 1:3878 in males in the first 67,835 screened newborns. […] Adrenal insufficiency is reported to occur in the majority of males with ALD. While VLCFA begin to accumulate during the fetal period, there are no reports of adrenal insufficiency at birth. The earliest reports of biochemical adrenal insufficiency are at 5 weeks and 3.5 months of age. California newborn screening reported 14 patients had abnormal ACTH testing in the first three plus years of follow-up and five patients were treated with glucocorticoids. The incidence of adrenal insufficiency in males with ALD is estimated to be 80â86%, with a peak onset reported between 3 and 10 years of age.
#7 Monitoring for and Management of Endocrine Dysfunction in Adrenoleukodystrophy
https://www.mdpi.com/2409-515X/8/1/18
Adrenoleukodystrophy (ALD) is the most common peroxisomal disorder and has a heterogeneous clinical presentation, impacting the nervous system, adrenal cortical function, and testicular function. New York State initiated newborn screening for ALD on 30 December 2013. Since that time, ALD has been added to the Recommended Uniform Screening Panel, and newborn screening has expanded to twenty-four states and the District of Columbia, as well as to the Netherlands. Newborn screening has the benefit of detecting males prior to the onset of symptoms and allowing for therapeutic interventions to prevent the most severe consequences of ALD. […] Historically, ALD was described as an X-linked recessive condition. The most severe presentations of ALD occur in males, but 80% of females with ALD manifest milder myelopathy symptoms by the age of 60 years. Prior to the introduction of newborn screening, the incidence of ALD in the United States was described to be 1:21,000 males and 1:16,800 females. A retrospective study of the US Childrenâs Hospital Associationâs Pediatric Health Information System database noted higher frequencies of ABCD1 pathogenic variants in those of Latino and African descent, despite higher diagnostic rates in those of non-Hispanic Caucasian descent, suggesting a potential racial bias in diagnosis prior to newborn screening.
#7 Monitoring for and Management of Endocrine Dysfunction in Adrenoleukodystrophy
https://www.mdpi.com/2409-515X/8/1/18
Newborn screening has allowed for the identification of those at high risk for adrenal insufficiency prior to the onset of symptoms, making it an ideal condition to add to newborn screening panels. Protocols vary among states, but all measure VLCFA from a filter paper specimen and have a confirmatory measurement as a second-tier test. Once an infant is identified by newborn screening, most statesâ protocols include referral to a metabolic center for confirmatory testing and genetic counseling. […] Once confirmed to have ALD, referral to pediatric endocrinology for adrenal insufficiency surveillance should not be delayed given the reports of early biochemical adrenal insufficiency and inability to predict which male infants will develop adrenal insufficiency early. An initial protocol suggested drawing ACTH and cortisol levels every 6 months. The frequency of screening was spaced to every 4â6 months thereafter. There are no recommendations for screening females with ALD for adrenal insufficiency, as the reported incidence is low.
#8 Clinical presentations |
https://adrenoleukodystrophy.info/clinical-diagnosis/clinical-presentations
The overall incidence of adrenoleukodystrophy is approximately 1 in 17,000 newborns. Adrenoleukodystrophy has been reported in all European and Latin American countries, China, Japan, India, Israel, Saudi Arabia, and in all ethnic groups, including African Americans, Native Americans, and Maori. […] The number of presymptomatic men decreases with age. It is important that a physician see these patients frequently. Follow-up of pre-symptomatic boys and men with adrenoleukodystrophy is important for two reasons: 1) early detection of adrenal insufficiency, and 2) early detection of cerebral ALD by brain MRI to propose allogeneic hematopoietic stem cell transplantation (HSCT) if an HLA-matched donor or cord blood is available. […] A newborn male patient has a 35-40% risk of developing cerebral ALD between the ages of 3 and 18 years, but cerebral ALD can also occur in adulthood.
#9 Adrenoleukodystrophy (ALD) Market Size & Share 2034
https://www.imarcgroup.com/adrenoleukodystrophy-market
Adrenoleukodystrophy incidence is higher in patients of Latino or African origin. […] X-linked adrenoleukodystrophy is the most common peroxisomal condition, with an estimated birth frequency of 1 in 17,000 (male and female). […] In the United States, one in every 21,000 men is thought to have adrenoleukodystrophy, whereas one in every 16,800 women is expected to be a carrier. […] Men are more likely to develop adrenoleukodystrophy. […] Most cases are identified in childhood; however, a considerable proportion of cases appear in young adults (usually in their late 20s). […] IMARC Group’s new report provides an exhaustive analysis of the adrenoleukodystrophy market in the United States, EU4 (Germany, Spain, Italy, and France), United Kingdom, and Japan. This includes treatment practices, in-market, and pipeline drugs, share of individual therapies, market performance across the seven major markets, market performance of key companies and their drugs, etc.
#10 Epidemiology of X-linked adrenoleukodystrophy in Japan | Journal of Human Genetics
https://www.nature.com/articles/jhg200297
To clarify the epidemiology of X-linked adrenoleukodystrophy (ALD) in Japan, we performed a questionnaire survey. […] The incidence of X-linked ALD in Japan was estimated to be between 1 : 30 000 and 1 : 50 000 boys, similar to previous reports. […] These data will help in understanding the natural history of X-linked ALD.
#11 Childhood cerebral adrenoleukodystrophy (CCALD) in France: epidemiology, natural history, and burden of disease – A population-based study | Orphanet Journal of Rare Diseases | Full Text
https://ojrd.biomedcentral.com/articles/10.1186/s13023-023-02843-x
X-linked adrenoleukodystrophy (ALD) is a rare metabolic and neurodegenerative disorder belonging to the group of leukodystrophies, with an estimated incidence around 1:25 000 newborns worldwide, mostly among men. […] To date, there is a lack of data regarding CCALD epidemiology, natural history, and current management in France. This knowledge is crucial for the development of new therapies such as gene therapies. […] The necessity of a precocious management with HSCT highlight the potential benefits of including an expanded screening program among newborns, coupled with family screenings when a mutation is detected. […] In current study, median annual incidence was 4, and reached expected incidence only twice. […] X-linked ALD incidence in France is estimated around 1/17,000 births, of whom 35-40% might develop CCALD, leading to an expected annual incidence between 5 and 6 young boys in France.
#11 Childhood cerebral adrenoleukodystrophy (CCALD) in France: epidemiology, natural history, and burden of disease – A population-based study | Orphanet Journal of Rare Diseases | Full Text
https://ojrd.biomedcentral.com/articles/10.1186/s13023-023-02843-x
This study is the first to directly assess HCRU and related costs through real-life data in France. […] Annualized costs remain a robust approach to estimate CCALD burden. […] When analyzing cost evolution with time and disease progression, two completely different patterns are expected between patients with HSCT and those without HSCT. […] This study estimated the number of CCALD patients in France, their clinical characteristics, therapeutic management and medium- and long-term evolution, through a follow-up analysis of 6 years in median. […] HSCT in CCALD disease management has been shown as primordial when performed early enough to prevent symptoms and MFDs.
#12 X-linked adrenoleukodystrophy: MedlinePlus GeneticsLock
https://medlineplus.gov/genetics/condition/x-linked-adrenoleukodystrophy/
The prevalence of X-linked adrenoleukodystrophy is 1 in 15,000 individuals worldwide. This condition occurs with a similar frequency in all populations. […] X-linked adrenoleukodystrophy is inherited in an X-linked pattern. A condition is considered X-linked if the altered gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes in each cell. In males (who have only one X chromosome), one altered copy of the ABCD1 gene in each cell is sufficient to cause X-linked adrenoleukodystrophy. Additionally, affected males pass the altered gene to all of their daughters but none of their sons. […] Because females have two copies of the X chromosome, one altered copy of the ABCD1 gene in each cell usually does not cause features of X-linked adrenoleukodystrophy that are as severe as those in affected males. Most affected females with one altered copy of the gene develop features of the adrenomyeloneuropathy type. The signs and symptoms of X-linked adrenoleukodystrophy tend to appear at a later age in affected females than in affected males. Additionally, affected females have a 50 percent chance of passing the altered gene to each of their children.
#13 Practical information for females with the ALD gene – Alex – The Leukodystrophy Charity
https://alextlc.org/practical-information-for-female-carriers-of-ald-amn/
About 80% of women with the ALD gene will develop some symptoms of AMN during their lifetime. […] The symptoms usually develop at an older age in women than in men, and progress more slowly. […] In females, the development of either cerebral leukodystrophy or adrenal insufficiency is extremely rare and has only been described in a very few isolated cases. […] About 80% of females with the gene will develop some AMN symptoms later in life. Symptoms can vary in severity. […] If you have children, each child has a 50% chance of having the ALD gene. […] If you are a female with the ALD gene and have a boy, there is a 50% chance that he will be at risk of developing the life-threatening disease ALD as a child or developing AMN in later life.
#14 Adrenoleukodystrophy – Market Insight, Epidemiology, and Market Forecast – 2034
https://www.giiresearch.com/report/del1632479-adrenoleukodystrophy-market-insight-epidemiology.html
In 2023, the United States accounted for the largest Adrenoleukodystrophy market size (~USD 400 Million) in comparison to EU4 (Germany, Spain, Italy, France), the United Kingdom, and Japan. […] Adrenoleukodystrophy (ALD) is a rare genetic disorder that predominantly affects male during childhood. In 2023, around 60% of ALD cases were diagnosed in male based on the gender-specific prevalence of the disease in the 7MM. […] According to the findings, adrenoleukodystrophy in the 7MM was found to be more prevalent in male compared to female. […] As per DelveInsight’s estimates, total diagnosed prevalent cases of adrenoleukodystrophy in the United States was more than 30% of cases diagnosed across the 7MM in 2023. […] Among the EU4 and the UK, the total prevalent population of adrenoleukodystrophy patients were the highest in Germany with approximately 25% cases, followed by France and UK in 2023. […] DelveInsight’s consultant estimates that the cerebral ALD will contribute the maximum number of cases in the United States in 2023.
#15 X-linked Adrenoleukodystrophy (ALD) | Division of Medical Genetics | Stanford Medicine
https://med.stanford.edu/medicalgenetics/Metabolicdisease/ALD.html
X-linked Adrenoleukodystrophy is a genetic condition that may be found on Newborn Screening, or can be diagnosed based on a variety of symptoms. […] Importantly, potentially life-saving therapies are available if the diagnosis of X-linked ALD is made before the onset of symptoms. This is the reason the condition was added to Calinfornia Newborn Screen (NBS) in February, of 2016. […] After your son has been diagnosed with X-linked ALD, regular follow-up is needed. […] Expert ALD clinicians have designed MRI and lab surveillance schedules to detect ALD complications before they cause permanent disability. […] In other words, the goal of ALD surveillance is to keep your son as healthy and active as other boys his age.
#16 Psychological Impact of Presymptomatic X-Linked ALD Diagnosis and Surveillance: A Small Qualitative Study of Patient and Parent Experiences
https://www.mdpi.com/2409-515X/10/4/73
X-linked adrenoleukodystrophy (ALD) is a rare metabolic disorder. The incidence has been reported as between 0.8 and 6 per 100,000 in epidemiological studies. […] To ensure timely treatment of adrenal insufficiency and cALD, patients who have been diagnosed presymptomatically are kept under surveillance throughout childhood and adulthood. This includes screening for Addison’s disease with hormone measurements or ACTH-stimulation tests every 3â12 months (depending on age) and cerebral magnetic resonance imaging (MRI) every six months during childhood and every 12 months in adulthood. […] Given the potential benefits of early diagnosis and treatment of ALD, the state of New York became the first to implement newborn screening (NBS) for ALD, following the passage of Aidens Law in 2013. Since then, 44 American states, Taiwan, and the Netherlands have included ALD in their NBS program. Japan, Italy, and China currently have ongoing pilot studies.
#16 Psychological Impact of Presymptomatic X-Linked ALD Diagnosis and Surveillance: A Small Qualitative Study of Patient and Parent Experiences
https://www.mdpi.com/2409-515X/10/4/73
While early detection and surveillance enable potentially lifesaving treatment of ALD, they also necessitate extensive follow-up. Due to the lack of prognostic biomarkers, predicting the disease course for individual patients with ALD is impossible, leading to uniform extensive follow-up for all pre-symptomatic males diagnosed with the condition.
#17 Newborn Screening for Adrenoleukodystrophy | Medical School
https://med.umn.edu/pediatrics/programs-centers-institutes/leukodystrophy-center/adrenoleukodystrophy-ald/newborn-screening
In 2013, New York became the first state in the United States to test all newborns for adrenoleukodystrophy. […] Pennsylvania started newborn screening for ALD on April 2017. […] Rhode Island started newborn screening for ALD on April 2019. […] On May 7, 2015, Kathy Switow, Elisa Seeger, and Jenny Weldon attended the Genetics Advisory Committee meeting in Tennessee. […] Texas started newborn screening in August 2019. […] Utah will begin newborn screening for ALD in 2020. […] Vermont started newborn screening for ALD in May 2019. […] The Washington State Department of Health added ALD to the newborn screening panel on March 1, 2018. […] Washington, D.C. started newborn screening for ALD in September 2018.
#17 Newborn Screening for Adrenoleukodystrophy | Medical School
https://med.umn.edu/pediatrics/programs-centers-institutes/leukodystrophy-center/adrenoleukodystrophy-ald/newborn-screening
We believe the availability of newborn screening will prove extremely important in the identification of patients at risk, and in minimizing the long-term effects of their disease. […] In February 2017, adrenoleukodystrophy was added to the Recommended Uniform Screening Panel, which is the list of disorders that are screened at birth and recommended by the Secretary of the Department of Health and Human Services in the United States. […] On June 15, 2016, thanks to tireless work by Shanna and Nick Quimby, the Minnesota Department of Health (MDH) added adrenoleukodystrophy to its list of conditions for which all newborns in the state are screened. […] The California Department of Public Healths Genetic Disease Screening Program (GDSP) began screening for adrenoleukodystrophy in mid-September 2016.
#18 Facts about ALD |
https://adrenoleukodystrophy.info/clinical-diagnosis/facts-on-ald
ALD is a global disease that affects people of all ethnicities and regions. It is estimated to affect approximately 1 in 15,000 newborns worldwide. […] Early diagnosis is critical to saving lives in ALD, and newborn screening plays a pivotal role in enabling prospective monitoring of adrenal function and the onset of cerebral ALD. […] On December 30, 2013, the State of New York began screening newborns for ALD. […] In February 2016, ALD was added to the United States Recommended Uniform Screening Panel (RUSP). […] Following the inclusion in the RUSP, other states and countries have initiated newborn screening programs or processes to add ALD to existing programs.
#19 Adrenoleukodystrophy | MedLink Neurology
https://www.medlink.com/articles/adrenoleukodystrophy
Because there is currently no definite genotype-phenotype correlation, once the patient is diagnosed with suspicious variants in the gene, they should be screened regularly for both adrenal insufficiency and development of cerebral adrenoleukodystrophy. It is recommended that all patients be screened for adrenal insufficiency every 3 to 4 months in the first 2 years of life and every 4 to 6 months thereafter. Additionally, a consensus meeting suggested that individuals with adrenoleukodystrophy have their first noncontrasted MRI between 12 to 18 months followed by repeat noncontrasted MRI between 12 to 30 months and 12 months after the first. However, as the risk for the development of cerebral adrenoleukodystrophy sharply increases after the age of 3, it is recommended that individuals get contrasted MRIs every 6 months until they turn 12 years of age. MRIs should be performed every year thereafter. If a lesion is identified during this time, the individual should undergo contrasted MRIs every 3 months to ensure they do not develop inflammatory demyelination, with urgent referral to a transplant center if they do.
#20 Management and prognosis of X-linked adrenoleukodystrophy – UpToDate
https://www.uptodate.com/contents/management-and-prognosis-of-x-linked-adrenoleukodystrophy/print
X-linked adrenoleukodystrophy (ALD) is a peroxisomal disorder of beta-oxidation that results in accumulation of very long-chain fatty acids (VLCFAs) in all tissues. Patients with ALD are asymptomatic at birth but may develop adrenal failure, leukodystrophy, and/or myeloneuropathy (spinal cord disease and peripheral neuropathy). Disease manifestations and disease severity are highly variable among patients. […] Patients diagnosed with ALD should be monitored for disease manifestations (leukodystrophy, myeloneuropathy, adrenal insufficiency), as detailed in the sections that follow (figure 1). […] MRI surveillance for leukodystrophy â All neurologically asymptomatic males with confirmed ALD should undergo surveillance neuroimaging with brain magnetic resonance imaging (MRI); over half of males will eventually develop a progressive leukodystrophy, the clinical effects of which may be mitigated by early treatment. […] Routine surveillance in females is not recommended as leukodystrophy is rare in females.
#21 Adrenoleukodystrophy (ALD) | Boston Children’s Hospital
https://www.childrenshospital.org/conditions/adrenoleukodystrophy-ald
Adrenoleukodystrophy (ALD) is a rare genetic condition that affects males and females differently. In childhood, boys are primarily affected. Girls are not typically affected, though they may develop symptoms as adults. […] Cerebral adrenoleukodystrophy, also known as cerebral ALD or CALD, affects the brain, typically during childhood. It occurs in about 1 in 21,000 boys between ages 4 and 10, affecting about 35 to 40 percent of boys with the ABCD1 mutation. Females with the ABCD1 mutation are highly unlikely to develop CALD. […] Many states now include ALD in routine newborn screening, or will be starting soon, allowing the disease to be caught and treated early. […] A newborn screening test was added to the United States Recommended Uniform Newborn Screening Panel in 2016 and is currently is available in many states. It detects elevated VLCFA levels in the blood, a clear indicator of ALD. With newborn screening, boys at risk for CALD can be identified and treated early.
#22 MRI surveillance of boys with X-linked adrenoleukodystrophy identified by newborn screening: Meta-analysis and consensus guidelines | ToxStrategies
https://toxstrategies.com/publications/mri-surveillance-of-boys-with-x-linked-adrenoleukodystrophy-identified-by-newborn-screening-meta-analysis-and-consensus-guidelines/
Among boys with X-Linked adrenoleukodystrophy, a subset will develop childhood cerebral adrenoleukodystrophy (CCALD). […] We sought to establish evidence-based guidelines detailing the neuroimaging surveillance of boys with neurologically asymptomatic adrenoleukodystrophy. […] The overall mean age of CCALD diagnosis is 7.91 years old. […] The expert panel achieved 95.7% consensus on the following surveillance parameters: (a) Obtain an MRI between 12 and 18 months old. (b) Obtain a second MRI 1 year after baseline. (c) Between 3 and 12 years old, obtain a contrast-enhanced MRI every 6 months. (d) After 12 years, obtain an annual MRI. […] Boys with adrenoleukodystrophy identified early in life should be monitored with serial brain MRIs during the period of highest risk for conversion to CCALD.
#23 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
With an estimated birth incidence of 1 in 17,000 newborns (male and female), X-ALD is the most common peroxisomal disorder. It occurs in all regions of the world. Now that newborn screening has become technically feasible and may be implemented in some parts of the world, the true prevalence might be even higher. […] A diagnosis of X-ALD must be followed by extended family screening together with a geneticist. This enables the detection of: 1) heterozygous women who can be offered prenatal or in some countries preimplantation diagnosis for future pregnancies, and 2) boys or adult males who are asymptomatic but at risk to develop cerebral demyelination or adrenocortical insufficiency. It is important to detect these complications as early as possible for treatment, as described in the section on clinical management. […] It is estimated that over a period of 10 years about 20% of patients with AMN will progress to a cerebral phenotype.
#24 Comprehensive Adrenoleukodystrophy (ALD) Clinic | Medical School
https://med.umn.edu/pediatrics/programs-centers-institutes/leukodystrophy-center/adrenoleukodystrophy-ald
The availability of newborn screening will prove extremely important in the identification of patients at risk, and in minimizing the long-term effects of their disease. […] Currently many states have added ALD to diseases being screened for at birth (newborn screening). […] The ALD National Registry at the University of Minnesota strives to be the worlds largest storehouse of clinical information, MRI scans, and biological samples related to ALD. We believe this will help researchers throughout the world better understand the natural history of the disease, including factors related to the onset and progression of disease. […] This is a prospective, non-therapeutic protocol designed to create and maintain a registry of participants with Adrenoleukodystrophy (ALD) and known/presumed carriers of ALD.
#25 Global Adrenoleukodystrophy (ALD) Market Insights 2017-2030 – Epidemiology, Pipeline, Marketed & Emerging Drugs, Reimbursement Scenario, Unmet Needs, Competitive Intelligence – ResearchAndMarkets.com
https://www.businesswire.com/news/home/20200701005717/en/Global-Adrenoleukodystrophy-ALD-Market-Insights-2017-2030—Epidemiology-Pipeline-Marketed-Emerging-Drugs-Reimbursement-Scenario-Unmet-Needs-Competitive-Intelligence—ResearchAndMarkets.com
This report delivers an in-depth understanding of the Adrenoleukodystrophy, historical and forecasted epidemiology as well as the Adrenoleukodystrophy market trends in the United States, EU5 (Germany, Spain, Italy, France, and the United Kingdom) and Japan. […] The disease epidemiology covered in the report provides historical as well as forecasted epidemiology segmented by Total Prevalent Population of Adrenoleukodystrophy in the 7MM, Gender-specific Prevalence of Adrenoleukodystrophy in the 7MM, Gender-specific Diagnosed Prevalence of Adrenoleukodystrophy in the 7MM, and Type-specific Diagnosed Prevalence of ALD in Males in the 7MM. The epidemiology section covers the 7MM countries, the United States, EU5 countries (Germany, France, Italy, Spain, and the United Kingdom), and Japan from the year 2017 to 2030.
#26 Global Adrenoleukodystrophy (ALD) Epidemiology Markets
https://www.globenewswire.com/news-release/2020/12/07/2140478/0/en/Global-Adrenoleukodystrophy-ALD-Epidemiology-Markets-2017-2030.html
The „Adrenoleukodystrophy (ALD) – Epidemiology Forecast to 2030” report delivers an in-depth understanding of the disease, historical and forecasted Adrenoleukodystrophy epidemiology in the 7MM, i.e., the United States, EU5 (Germany, Spain, Italy, France, and the United Kingdom), and Japan. […] As per the publisher’s analysis, in 2017, the total prevalent population of Adrenoleukodystrophy in the 7MM was 55,242. […] Among the European five countries, Germany had the highest diagnosed prevalent population of ALD with 1,895 cases, followed by France and the United Kingdom. On the other hand, Italy had the lowest diagnosed prevalent population of 1,126 in 2017. […] The report provides insight into the historical and forecasted patient pool for seven major markets covering the United States, EU5 (Germany, France, Italy, Spain, and the UK), and Japan.
#27 Adrenoleukodystrophy Market Forecast 2034: FDA Approvals, Clinical Trials, Epidemiology and Companies by DelveInsight
https://www.einpresswire.com/article/715240984/adrenoleukodystrophy-market-forecast-2034-fda-approvals-clinical-trials-epidemiology-and-companies-by-delveinsight
Adrenoleukodystrophy epidemiology section provides insights into the historical and current Adrenoleukodystrophy patient pool and forecasted trends for seven individual major countries. It helps to recognize the causes of current and forecasted trends by exploring numerous studies and views of key opinion leaders. This part of the Adrenoleukodystrophy market report also provides the diagnosed patient pool, trends, and assumptions. […] According to DelveInsight, the Adrenoleukodystrophy market in 7MM is expected to witness a major change in the study period 2020-2034.
#28 Adrenoleukodystrophy in the Differential Diagnosis of Boys Presenting with Primary Adrenal Insufficiency without Adrenal Antibodies – Journal of Clinical Research in Pediatric Endocrinology
https://jcrpe.org/articles/adrenoleukodystrophy-in-the-differential-diagnosis-of-boys-presenting-with-primary-adrenal-insufficiency-without-adrenal-antibodies/doi/jcrpe.galenos.2020.2020.0214
Adrenoleukodystrophy (ALD) is an X-linked, metabolic disorder caused by deficiency of peroxisomal ALD protein resulting in accumulation of very-long chain fatty acids (VLCFA), primarily in the adrenal cortex and central nervous system. Approximately 70-80% of boys with ALD have impaired adrenal function prior to the onset of neurologic symptoms. […] ALD was added to the recommended uniform screening panel in the United States in 2016, but newborn screening (NBS) remains limited, both within the US and worldwide. Therefore, early identification of ALD remains challenging due to nonspecific initial symptoms that overlap with other medical and developmental issues. […] Early detection of CALD is critical since allogeneic hematopoietic stem cell transplantation (HSCT) has the potential to stabilize cerebral disease progression, but is only effective if performed in the early stages of cerebral disease.
#29 Adrenoleukodystrophy in the Differential Diagnosis of Boys Presenting with Primary Adrenal Insufficiency without Adrenal Antibodies – Journal of Clinical Research in Pediatric Endocrinology
https://www.jcrpe.org/articles/adrenoleukodystrophy-in-the-differential-diagnosis-of-boys-presenting-with-primary-adrenal-insufficiency-without-adrenal-antibodies/doi/jcrpe.galenos.2020.2020.0214
Given this need for early ALD diagnosis and monitoring for CALD, ALD should be included in the differential diagnosis of boys presenting with PAI without adrenal antibodies. […] In retrospective analyses of boys with ALD, PAI was the presenting and only sign in 25-37% of patients. There were delays of between 1 and 10 years between diagnosis of PAI and diagnosis of ALD for approximately half of the boys in the study. […] These data emphasize that all boys with unexplained PAI should be screened for ALD. […] Although NBS programs will assist in early identification and surveillance of boys with ALD, the potential for delayed diagnosis persists where NBS is not available and where absence of family history precludes family screening.
#30 Our Focus: Cerebral Adrenoleukodystrophy (CALD) | bluebird bio
https://www.bluebirdbio.com/our-focus/cerebral-adrenoleukodystrophy
Adrenoleukodystrophy (ALD) is estimated to affect 1 in 5,000 to 1 in 17,000 newborns (both male and female), and approximately 1 in 20,000 to 1 in 30,000 newborn males. CALD develops in approximately 40% of affected boys and in a smaller number of adult men. […] Currently, there is no way to predict which boys with ALD will develop CALD. Fortunately, however, the early stages of CALD can be detected by brain MRI in boys with known ALD, even when they don’t have any noticeable symptoms. Current guidelines recommend that all boys diagnosed with ALD are monitored regularly with MRIs. […] Newborn screening for ALD is vital to enable early diagnosis and treatment. In the U.S., newborn screening for ALD was added to the Department of Health and Human Services Recommended Universal Screening Panel in 2016 and is being successfully implemented across the country as states adopt this as part of their universal newborn screening programs.
#31 Abstract Details
https://www.aan.com/MSA/Public/Events/AbstractDetails/51084
Though X-ALD has historically been considered a childhood disease managed by pediatric neurologists, it is the most common leukodystrophy diagnosed in adulthood. […] Growing numbers of both male and female adult patients are reaching diagnosis due to increased inclusion on state newborn screening panels and more widespread use of genetic testing. […] Routine surveillance for adrenal insufficiency and onset of cerebral ALD should be performed systematically to avoid preventable morbidity and mortality. […] We propose strategies for lab and imaging surveillance, symptom management, and identification of appropriate candidates for hematopoietic stem cell transplant or investigational treatments in adults with X-ALD/AMN.