Materiały źródłowe

• #1 Metachromatic Leukodystrophy | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/25045

  The prevalence of metachromatic leukodystrophy ranges from 1/40,000 to 1/100,000 in the northern European and North American populations. Incidence is estimated to be 1/40,000 births in the United States of America. There is no sexual and racial predilection. The disease is categorized based on the age of onset. […] Metachromatic leukodystrophy is an autosomal recessive lysosomal disorder that results in a buildup of sulfatides that leads to the destruction of the myelin sheath, leading to progressive demyelination of the central and peripheral nervous system.

• #2 A systematic review on the birth prevalence of metachromatic leukodystrophy – PubMed

  https://pubmed.ncbi.nlm.nih.gov/38383398/

  Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage disease caused by deficiency in arylsulfatase A (ASA) activity arising primarily from ASA gene (ARSA) variants. […] Epidemiological data were sought to address knowledge gaps and to inform decisions regarding the clinical development of an investigational drug. […] To synthesize all available estimates of MLD incidence and birth prevalence worldwide and in selected countries, Ovid MEDLINE and Embase were searched systematically (March 11, 2022) using a population, intervention, comparator, outcome, time and setting framework, complemented by pragmatic searching to reduce publication bias. […] Of the 31 studies included, 14 reported birth prevalence (13 countries in Asia-Pacific, Europe, the Middle East, North America and South America), one reported prevalence and none reported incidence. Birth prevalence per 100,000 live births ranged from 0.16 (Japan) to 1.85 (Portugal).

• #3 Metachromatic leukodystrophy – Wikipedia

  https://en.wikipedia.org/wiki/Metachromatic_leukodystrophy

  The incidence of metachromatic leukodystrophy is estimated to occur in 1 in 40,000 to 1 in 160,000 individuals worldwide. […] There is a much higher incidence in certain genetically isolated populations, such as 1 in 75 in Habbanites (a small group of Jews who immigrated to Israel from southern Arabia), 1 in 2,500 in the western portion of the Navajo Nation, and 1 in 8,000 among Arab groups in Israel. […] As an autosomal recessive disease, 1 in 40,000 equates to a 1 in 100 carrier frequency in the general population. […] In the US, there are an estimated 3,600 MLD births per year, with 1,900 alive; in Europe 3,100, and worldwide 49,000 alive. […] MLD is considered a rare disease in the US and other countries.

• #4 Metachromatic leukodystrophy: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/metachromatic-leukodystrophy/

  Metachromatic leukodystrophy is reported to occur in 1 in 40,000 to 160,000 individuals worldwide. The condition is more common in certain genetically isolated populations: 1 in 75 in a small group of Jews who immigrated to Israel from southern Arabia (Habbanites), 1 in 2,500 in the western portion of the Navajo Nation, and 1 in 8,000 among Arab groups in Israel. […] The most common form of metachromatic leukodystrophy, affecting about 50 to 60 percent of all individuals with this disorder, is called the late infantile form. This form of the disorder usually appears in the second year of life. Affected children lose any speech they have developed, become weak, and develop problems with walking (gait disturbance). As the disorder worsens, muscle tone generally first decreases, and then increases to the point of rigidity. Individuals with the late infantile form of metachromatic leukodystrophy typically do not survive past childhood.

• #5 Metachromatic Leukodystrophy | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/25045

  The prevalence of metachromatic leukodystrophy ranges from 1/40,000 to 1/100,000 in the northern European and North American populations. Incidence is estimated to be 1/40,000 births in the United States of America. There is no sexual and racial predilection. The disease is categorized based on the age of onset. […] Metachromatic leukodystrophy is an autosomal recessive lysosomal disorder that results in a buildup of sulfatides that leads to the destruction of the myelin sheath, leading to progressive demyelination of the central and peripheral nervous system.

• #6 Metachromatic Leukodystrophy: Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/951840-overview

  The incidence of metachromatic leukodystrophy (MLD) is estimated to be 1 case per 40,000 births in the United States. […] Morbidity and mortality rates vary with each form of the disease. In general, young patients have the most rapidly progressive disease, whereas patients with adult onset MLD experience a more chronic and insidious progression of disease. […] No differences have been identified on the basis of race or sex. […] Patients with the late infantile form of MLD are usually aged 4 years or younger and typically present initially with gait disturbances, loss of motor developmental milestones, optic atrophy, and diminished deep tendon reflexes. […] Patients with the early juvenile form of MLD (4-6 years) tend to present with loss of motor developmental milestones; the most obvious signs are gait disturbances, ataxia, hyperreflexia followed by hyporeflexia, seizures, and decreased cognitive function.

• #7 Metachromatic Leukodystrophy | Concise Medical Knowledge

  https://www.lecturio.com/concepts/metachromatic-leukodystrophy/

  Metachromatic leukodystrophy (MLD) is a rare, autosomal recessive inherited condition. […] The incidence is 1 in 40,000 live births in the United States. […] There is no racial or sexual predilection. […] MLD is the most common form of inherited leukodystrophy.

• #8 Orphanet: Metachromatic leukodystrophy

  https://www.orpha.net/en/disease/detail/512

  A rare lysosomal disease characterized by accumulation of sulfatides in the central and peripheral nervous system due to deficiency of the enzyme arylsulfatase A, leading to demyelination. […] Prevalence: 1-9 / 1 000 000 […] Research activities on this disease […] Registry(ies) (27)

• #9 A systematic review on the birth prevalence of metachromatic leukodystrophy – PubMed

  https://pubmed.ncbi.nlm.nih.gov/38383398/

  Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage disease caused by deficiency in arylsulfatase A (ASA) activity arising primarily from ASA gene (ARSA) variants. […] Epidemiological data were sought to address knowledge gaps and to inform decisions regarding the clinical development of an investigational drug. […] To synthesize all available estimates of MLD incidence and birth prevalence worldwide and in selected countries, Ovid MEDLINE and Embase were searched systematically (March 11, 2022) using a population, intervention, comparator, outcome, time and setting framework, complemented by pragmatic searching to reduce publication bias. […] Of the 31 studies included, 14 reported birth prevalence (13 countries in Asia-Pacific, Europe, the Middle East, North America and South America), one reported prevalence and none reported incidence. Birth prevalence per 100,000 live births ranged from 0.16 (Japan) to 1.85 (Portugal).

• #10 A systematic review on the birth prevalence of metachromatic leukodystrophy | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-024-03044-w

  Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage disease caused by deficiency in arylsulfatase A (ASA) activity arising primarily from ASA gene (ARSA) variants. […] Epidemiological data were sought to address knowledge gaps and to inform decisions regarding the clinical development of an investigational drug. […] Of the 31 studies included, 14 reported birth prevalence (13 countries in AsiaPacific, Europe, the Middle East, North America and South America), one reported prevalence and none reported incidence. […] Birth prevalence per 100,000 live births ranged from 0.16 (Japan) to 1.85 (Portugal). […] The distribution of clinical subtypes reported in cases diagnosed over various time periods in 17 studies varied substantially, but late-infantile and juvenile MLD accounted for at least two-thirds of cases in most studies.

• #11 The natural history and burden of illness of metachromatic leukodystrophy: a systematic literature review | European Journal of Medical Research | Full Text

  https://eurjmedres.biomedcentral.com/articles/10.1186/s40001-024-01771-1

  Metachromatic leukodystrophy (MLD; OMIM 250100 and 249900) is a rare lysosomal storage disease caused by deficient arylsulfatase A activity, leading to accumulation of sulfatides in the nervous system. […] The incidence (birth prevalence) of MLD varies across populations but has been estimated to be between 1 in 40,000 and 1 in 160,000. […] Epidemiology of MLD by geographic regions, quantitative cognitive data, data on the differences between early- and late-juvenile MLD, and humanistic or economic outcomes were limited. […] The birth incidence and birth prevalence of MLD were reported in eight and four studies, respectively. […] The Czech Republic was reported to have the lowest birth prevalence of MLD at 0.69 per 100,000 births, and Poland was reported as having the highest birth prevalence of 4.1 per 100,000 births.

• #12 Metachromatic leukodystrophy – Wikipedia

  https://en.wikipedia.org/wiki/Metachromatic_leukodystrophy

  The incidence of metachromatic leukodystrophy is estimated to occur in 1 in 40,000 to 1 in 160,000 individuals worldwide. […] There is a much higher incidence in certain genetically isolated populations, such as 1 in 75 in Habbanites (a small group of Jews who immigrated to Israel from southern Arabia), 1 in 2,500 in the western portion of the Navajo Nation, and 1 in 8,000 among Arab groups in Israel. […] As an autosomal recessive disease, 1 in 40,000 equates to a 1 in 100 carrier frequency in the general population. […] In the US, there are an estimated 3,600 MLD births per year, with 1,900 alive; in Europe 3,100, and worldwide 49,000 alive. […] MLD is considered a rare disease in the US and other countries.

• #13 Metachromatic leukodystrophy: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/metachromatic-leukodystrophy/

  Metachromatic leukodystrophy is reported to occur in 1 in 40,000 to 160,000 individuals worldwide. The condition is more common in certain genetically isolated populations: 1 in 75 in a small group of Jews who immigrated to Israel from southern Arabia (Habbanites), 1 in 2,500 in the western portion of the Navajo Nation, and 1 in 8,000 among Arab groups in Israel. […] The most common form of metachromatic leukodystrophy, affecting about 50 to 60 percent of all individuals with this disorder, is called the late infantile form. This form of the disorder usually appears in the second year of life. Affected children lose any speech they have developed, become weak, and develop problems with walking (gait disturbance). As the disorder worsens, muscle tone generally first decreases, and then increases to the point of rigidity. Individuals with the late infantile form of metachromatic leukodystrophy typically do not survive past childhood.

• #14 Frontiers | Metachromatic Leukodystrophy: Diagnosis, Modeling, and Treatment Approaches

  https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2020.576221/full

  Metachromatic leukodystrophy (MLD) is one of the most common leukodystrophies, and has a prevalence rate of 1 in 40,000–160,000 worldwide. In some isolated populations, the incidence of MLD is much higher. For example, in the group of Habbanite (Jews) it is estimated at 1 in 75, among the Navajo Indian people at 1 in 2,500, and among the Arab groups of Israel it is estimated at 1 in 8,000. […] In most cases, MLD is not included in the fetus and newborn genetic screening tests given that MLD is a rare disease. Commonly, the disease is diagnosed after birth, depending on the form of MLD. Only in cases where the parents know that their family carries the mutation (family history, development of the disease in previous children), diagnosis and treatment can begin. However, early diagnosis is critically important. The introduction of prenatal diagnosis and newborn screening could increase therapy efficacy, since the effectiveness of the treatment is significantly reduced after the onset of symptoms.

• #15 Metachromatic Leukodystrophy: What It Is, Causes & Symptoms

  https://my.clevelandclinic.org/health/diseases/6067-metachromatic-leukodystrophy

  MLD is rare. Researchers estimate that it affects 1 in every 40,000 people in the United States. MLD may be more common in certain isolated populations. For example, the Navajo have a higher prevalence rate of 1 in every 2,500 people. […] The prognosis (outlook) for metachromatic leukodystrophy is poor. Its a progressive disease, which means the symptoms spread and/or get worse over time. People with MLD eventually lose all muscle and mental functions, which results in death. […] The life expectancy of metachromatic leukodystrophy depends on the age at which a person is first diagnosed.

• #16 Disease: Metachromatic Leukodystrophy

  https://crisprmedicinenews.com/disease/card/metachromatic-leukodystrophy/

  MLD (all subtypes combined) is estimated to occur in between 1 in 40,000 and 1 in 160,000 people, however the true prevalence is unknown. The Navajo (a Native American people of the Southwestern United States), also have a higher prevalence rate of 1 in every 2,500 people. In certain populations in the Middle East, these numbers may be even higher (source: www.rarediseases.org).

• #17 Frontiers | Metachromatic Leukodystrophy: Diagnosis, Modeling, and Treatment Approaches

  https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2020.576221/full

  Metachromatic leukodystrophy (MLD) is one of the most common leukodystrophies, and has a prevalence rate of 1 in 40,000–160,000 worldwide. In some isolated populations, the incidence of MLD is much higher. For example, in the group of Habbanite (Jews) it is estimated at 1 in 75, among the Navajo Indian people at 1 in 2,500, and among the Arab groups of Israel it is estimated at 1 in 8,000. […] In most cases, MLD is not included in the fetus and newborn genetic screening tests given that MLD is a rare disease. Commonly, the disease is diagnosed after birth, depending on the form of MLD. Only in cases where the parents know that their family carries the mutation (family history, development of the disease in previous children), diagnosis and treatment can begin. However, early diagnosis is critically important. The introduction of prenatal diagnosis and newborn screening could increase therapy efficacy, since the effectiveness of the treatment is significantly reduced after the onset of symptoms.

• #18 Metachromatic Leukodystrophy – CAGS

  https://cags.org.ae/en/ctga-details/203/metachromatic-leukodystrophy

  Metachromatic Leukodystrophy (MLD) is an autosomal recessive leukodystrophy, characterized by a buildup of sulfatide fat in cells, especially in cells of the nervous system. […] A hospital register based study by Rajab et al. (2005) in Oman from 1993 to 2002 revealed that Metachromatic Leukodystrophy was diagnosed in 18 patients, with an observed incidence of 1 in 25,000 births. […] The subject of this study is a population from Habban (Arabian Peninsula, Southwest of Hadhramaut), an area with high frequency of MLD.

• #19 Population Carrier Rates of Pathogenic ARSA Gene Mutations: Is Metachromatic Leukodystrophy Underdiagnosed? | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0020218

  Metachromatic leukodystrophy (MLD) is a severe neurometabolic disease caused mainly by deficiency of arylsulfatase A encoded by the ARSA gene. Based on epidemiological surveys the incidence of MLD per 100 000 live births varied from 0.6 to 2.5. […] Taking into account ARSA gene mutation distribution among 60 Polish patients, the expected MLD birth prevalence in the general population (assuming no selection against homozygous fetuses) was estimated as 4.0/100 000 and 4.1/100 000, respectively for the 1st and the 2nd cohort with a pooled estimate of 4.1/100 000 (CI: 1.89.4) which was higher than the estimate of 0.38 per 100 000 live births based on diagnosed cases. […] The observed discrepancy between the measured incidence of metachromatic leukodystrophy and the predicted carriage rates suggests that MLD is substantially underdiagnosed in the Polish population.

• #20 Population Carrier Rates of Pathogenic ARSA Gene Mutations: Is Metachromatic Leukodystrophy Underdiagnosed? | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0020218

  The expected prevalence of fetuses conceived with two pathogenic ARSA mutations in Poland (4.1 per 100 000) is substantially higher than the birth prevalence of MLD based on diagnosed cases (0.38 per 100 000 live births as determined by us or 0.53 per 100 000 (1 in 189 000) as previously reported in Poland). […] This discrepancy between our estimate and observed incidence of MLD in Poland may have several causes. […] One possible reason for the discrepancy between observed and expected prevalence of MLD may be related to disease underdiagnosis, especially among patients with p.I179S mutation.

• #21 Metachromatic leukodystrophy – Wikipedia

  https://en.wikipedia.org/wiki/Metachromatic_leukodystrophy

  The incidence of metachromatic leukodystrophy is estimated to occur in 1 in 40,000 to 1 in 160,000 individuals worldwide. […] There is a much higher incidence in certain genetically isolated populations, such as 1 in 75 in Habbanites (a small group of Jews who immigrated to Israel from southern Arabia), 1 in 2,500 in the western portion of the Navajo Nation, and 1 in 8,000 among Arab groups in Israel. […] As an autosomal recessive disease, 1 in 40,000 equates to a 1 in 100 carrier frequency in the general population. […] In the US, there are an estimated 3,600 MLD births per year, with 1,900 alive; in Europe 3,100, and worldwide 49,000 alive. […] MLD is considered a rare disease in the US and other countries.

• #22 Metachromatic leukodystrophy. Case presentation | Revista Colombiana de Psiquiatría (English Edition)

  https://www.elsevier.es/es-revista-revista-colombiana-psiquiatria-english-edition–479-articulo-metachromatic-leukodystrophy-case-presentation-S2530312017300036

  Metachromatic leukodystrophy (MLD) is a rare demyelinating disease (prevalence 1:40,000), also called arylsulfatase A deficiency (ARS-A), which may present with neurological and psychiatric symptoms. […] MLD occurs with an estimated frequency of 1:40,000, although it is estimated that up to 16% of the general population may have an ARSA deficiency. […] Because it is a rare, heterogeneous disease with diverse clinical presentation and lack of clinical, neurophysiological and neuroradiological documentation, little is known about factors related to age of onset and the course of the disease, making it difficult to predict how each particular case will progress. […] The different ways in which the disease progresses are related to the type of mutation.

• #23 Metachromatic leukodystrophy: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/metachromatic-leukodystrophy/

  Metachromatic leukodystrophy is reported to occur in 1 in 40,000 to 160,000 individuals worldwide. The condition is more common in certain genetically isolated populations: 1 in 75 in a small group of Jews who immigrated to Israel from southern Arabia (Habbanites), 1 in 2,500 in the western portion of the Navajo Nation, and 1 in 8,000 among Arab groups in Israel. […] The most common form of metachromatic leukodystrophy, affecting about 50 to 60 percent of all individuals with this disorder, is called the late infantile form. This form of the disorder usually appears in the second year of life. Affected children lose any speech they have developed, become weak, and develop problems with walking (gait disturbance). As the disorder worsens, muscle tone generally first decreases, and then increases to the point of rigidity. Individuals with the late infantile form of metachromatic leukodystrophy typically do not survive past childhood.

• #24 Metachromatic leukodystrophy | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/metachromatic-leukodystrophy?embed_domain=external.radpair.com%2527%255B0%255D%2527%255B0%255Dfavicon.icoradiopaedia-icon-144.png&lang=us

  Metachromatic leukodystrophy has an estimated prevalence of ~1:100,000 and typically manifests between 12 to 18 months of age. The disease can sometimes be classified according to the time of onset: […] late infantile: most common ~65% (range 50-80%) […] juvenile (onset between 3-10 years) […] adult (after age 16).

• #25 Metachromatic leukodystrophy: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/metachromatic-leukodystrophy/

  Metachromatic leukodystrophy is reported to occur in 1 in 40,000 to 160,000 individuals worldwide. The condition is more common in certain genetically isolated populations: 1 in 75 in a small group of Jews who immigrated to Israel from southern Arabia (Habbanites), 1 in 2,500 in the western portion of the Navajo Nation, and 1 in 8,000 among Arab groups in Israel. […] The most common form of metachromatic leukodystrophy, affecting about 50 to 60 percent of all individuals with this disorder, is called the late infantile form. This form of the disorder usually appears in the second year of life. Affected children lose any speech they have developed, become weak, and develop problems with walking (gait disturbance). As the disorder worsens, muscle tone generally first decreases, and then increases to the point of rigidity. Individuals with the late infantile form of metachromatic leukodystrophy typically do not survive past childhood.

• #26 Metachromatic leukodystrophy | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/metachromatic-leukodystrophy?embed_domain=external.radpair.com%2527%255B0%255D%2527%255B0%255Dfavicon.icoradiopaedia-icon-144.png&lang=us

  Metachromatic leukodystrophy has an estimated prevalence of ~1:100,000 and typically manifests between 12 to 18 months of age. The disease can sometimes be classified according to the time of onset: […] late infantile: most common ~65% (range 50-80%) […] juvenile (onset between 3-10 years) […] adult (after age 16).

• #27 Metachromatic leukodystrophy: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/metachromatic-leukodystrophy/

  In 20 to 30 percent of individuals with metachromatic leukodystrophy, onset occurs between the age of 4 and adolescence. In this juvenile form, the first signs of the disorder may be behavioral problems and increasing difficulty with schoolwork. Progression of the disorder is slower than in the late infantile form, and affected individuals may survive for about 20 years after diagnosis. […] The adult form of metachromatic leukodystrophy affects approximately 15 to 20 percent of individuals with the disorder. In this form, the first symptoms appear during the teenage years or later. Often behavioral problems such as alcohol use disorder, drug abuse, or difficulties at school or work are the first symptoms to appear. The affected individual may experience psychiatric symptoms such as delusions or hallucinations. People with the adult form of metachromatic leukodystrophy may survive for 20 to 30 years after diagnosis. During this time there may be some periods of relative stability and other periods of more rapid decline.

• #28 Metachromatic leukodystrophy: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/metachromatic-leukodystrophy/

  In 20 to 30 percent of individuals with metachromatic leukodystrophy, onset occurs between the age of 4 and adolescence. In this juvenile form, the first signs of the disorder may be behavioral problems and increasing difficulty with schoolwork. Progression of the disorder is slower than in the late infantile form, and affected individuals may survive for about 20 years after diagnosis. […] The adult form of metachromatic leukodystrophy affects approximately 15 to 20 percent of individuals with the disorder. In this form, the first symptoms appear during the teenage years or later. Often behavioral problems such as alcohol use disorder, drug abuse, or difficulties at school or work are the first symptoms to appear. The affected individual may experience psychiatric symptoms such as delusions or hallucinations. People with the adult form of metachromatic leukodystrophy may survive for 20 to 30 years after diagnosis. During this time there may be some periods of relative stability and other periods of more rapid decline.

• #29 A systematic review on the birth prevalence of metachromatic leukodystrophy – PubMed

  https://pubmed.ncbi.nlm.nih.gov/38383398/

  In the three European studies with estimates stratified by clinical subtypes, birth prevalence was highest for late-infantile cases (0.31-1.12 per 100,000 live births). […] This review provides a foundation for further analysis of the regional epidemiology of MLD. Data gaps indicate the need for better global coverage, increased use of epidemiological measures (e.g. prevalence estimates) and more stratification of outcomes by clinical and genetic disease subtype.

• #30 A systematic review on the birth prevalence of metachromatic leukodystrophy | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-024-03044-w

  This review provides a foundation for further analysis of the regional epidemiology of MLD. […] It is typical to see birth prevalence ranges of 1.41.8 per 100,000 or 1 in 40,000 to 1 in 160,000 quoted in the literature; however, it is important to recognize regional and societal variations in the epidemiology of MLD that are biologically driven rather than a result of testing methodologies. […] The objective of this systematic review was to generate a qualitative synthesis of estimates of incidence, birth prevalence and prevalence of MLD in countries across the world, stratifying results by clinical subtype. […] The birth prevalence estimate by clinical subtype of MLD was highest for late-infantile cases in each of the three European studies reporting this breakdown. […] This systematic review highlights several data gaps that, if closed, could help to advance our understanding of the epidemiology of MLD.

• #31 Metachromatic leukodystrophy. Case presentation☆

  https://www.redalyc.org/journal/806/80651120007/html/

  The late-infantile subtype, described by Greenfield in 1933, is the most prevalent. […] In the juvenile form, the age of onset is usually between 4 and 6 years old. […] In the late-juvenile subtype, the disease usually begins between the ages of 6 and 16 years and progresses slowly. […] In the adult subtype the symptoms appear after the age of 16 years. […] In more than half of patients the age of onset of the disease is between 10 and 30 years, with symptoms similar to psychosis, including auditory hallucinations, delusions, altered thought processes and catatonia. […] The disease progresses with neurological symptoms such as seizures, chorea and dystonia that occur after the onset of psychiatric symptoms.

• #32 Frontiers | Metachromatic Leukodystrophy: Diagnosis, Modeling, and Treatment Approaches

  https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2020.576221/full

  Diagnosis of late onset forms of MLD is often more difficult. For instance, proper diagnosis is problematic as adult MLD is often mistaken for schizophrenia or other types of mental disorders, therefore delaying the beginning of therapy. […] To date, MLD is diagnosed by clinical manifestations, using genetic analysis for mutations in the ARSA and PSAP genes, magnetic resonance imaging (MRI) of the brain and biochemical tests of the ARSA enzymatic activity in skin fibroblasts, leukocytes and urine of patients.

• #33 About MLD Metachromatic Leukodystrophy | MLD Support Association UK

  https://www.mldsupportuk.org.uk/about-mld/

  There are many forms of Leukodystrophy, but Metachromatic Leukodystrophy (MLD) is one of the most common forms. The incidence of MLD is now estimated to occur in 1 case in 40,000 live births. […] Many clinicians believe that Adult-Onset MLD is currently much under-diagnosed.

• #34 Frontiers | Metachromatic Leukodystrophy: Diagnosis, Modeling, and Treatment Approaches

  https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2020.576221/full

  Metachromatic leukodystrophy (MLD) is one of the most common leukodystrophies, and has a prevalence rate of 1 in 40,000–160,000 worldwide. In some isolated populations, the incidence of MLD is much higher. For example, in the group of Habbanite (Jews) it is estimated at 1 in 75, among the Navajo Indian people at 1 in 2,500, and among the Arab groups of Israel it is estimated at 1 in 8,000. […] In most cases, MLD is not included in the fetus and newborn genetic screening tests given that MLD is a rare disease. Commonly, the disease is diagnosed after birth, depending on the form of MLD. Only in cases where the parents know that their family carries the mutation (family history, development of the disease in previous children), diagnosis and treatment can begin. However, early diagnosis is critically important. The introduction of prenatal diagnosis and newborn screening could increase therapy efficacy, since the effectiveness of the treatment is significantly reduced after the onset of symptoms.

• #35 Frontiers | Metachromatic Leukodystrophy: Diagnosis, Modeling, and Treatment Approaches

  https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2020.576221/full

  Metachromatic leukodystrophy (MLD) is one of the most common leukodystrophies, and has a prevalence rate of 1 in 40,000–160,000 worldwide. In some isolated populations, the incidence of MLD is much higher. For example, in the group of Habbanite (Jews) it is estimated at 1 in 75, among the Navajo Indian people at 1 in 2,500, and among the Arab groups of Israel it is estimated at 1 in 8,000. […] In most cases, MLD is not included in the fetus and newborn genetic screening tests given that MLD is a rare disease. Commonly, the disease is diagnosed after birth, depending on the form of MLD. Only in cases where the parents know that their family carries the mutation (family history, development of the disease in previous children), diagnosis and treatment can begin. However, early diagnosis is critically important. The introduction of prenatal diagnosis and newborn screening could increase therapy efficacy, since the effectiveness of the treatment is significantly reduced after the onset of symptoms.

• #36 Metachromatic Leukodystrophy |

  https://www.huntershope.org/family-care/leukodystrophies/metachromatic-leukodystrophy/

  Newborn screening for MLD is currently being validated in a medium-scale pilot study by University of Washington investigators. This would help in early detection of more individuals with MLD who could potentially benefit from transplant. […] All families and caregivers of individuals affected by Leukodystrophy, whether they qualify for transplant or not, should seek expert care through the Leukodystrophy Care Network, or LCN.

• #37 Consensus guidelines for the monitoring and management of metachromatic leukodystrophy in the United States – University of Iowa

  https://iro.uiowa.edu/esploro/outputs/journalArticle/Consensus-guidelines-for-the-monitoring-and/9984586459902771

  Metachromatic leukodystrophy (MLD) is a fatal, progressive neurodegenerative disorder caused by biallelic pathogenic mutations in the ARSA (Arylsulfatase A) gene. […] To meet the needs of the MLD community, a panel of MLD experts was established to develop disease-specific guidelines based on healthcare resources in the United States. […] The panel supported the development of newborn screening to accelerate the time to diagnosis and treatment. […] This document summarizes current guidance on the presymptomatic monitoring of children affected by MLD as well as the clinical management of symptomatic patients. Future data-driven evidence and evolution of these recommendations will be important to stratify clinical treatment options and improve clinical care.

• #38 New Horizons for Metachromatic Leukodystrophy with the Advent of Newborn Screening – European Medical Journal

  https://www.emjreviews.com/flagship-journal/symposium/new-horizons-for-metachromatic-leukodystrophy-with-the-advent-of-newborn-screening/

  During the symposium, the panellists discussed the applicability of the Wilson and Jungner criteria to metachromatic leukodystrophy (MLD), which they considered a strong candidate for newborn screening (NBS) thanks to the existing supporting evidence. This includes the availability of a screening test, the agreement on how to confirm diagnosis after positive screening, the presence of a prospective population-based newborn screening project that identified at least one infant with the condition, and the evidence that an early identification through NBS leads to better health outcomes. […] In the symposium, the speakers also reminded the audience of the existence of a validated three-tier screening algorithm of recent publication and the availability of two consensus guidelines that have been published in both the EU and the USA, and which unanimously support the implementation of NBS for MLD.

• #39 New Horizons for Metachromatic Leukodystrophy with the Advent of Newborn Screening – European Medical Journal

  https://www.emjreviews.com/flagship-journal/symposium/new-horizons-for-metachromatic-leukodystrophy-with-the-advent-of-newborn-screening/

  MLD is a rare inherited lysosomal storage disease affecting 1 in 100,000 newborns and caused by deficiency of arylsulfatase A (ARSA), due to mutations in the ARSA gene. […] The fast progression of the LI subtype of the disease (accounting for the majority of the MLD cases, or about 60% of the affected population), clearly highlights the importance of identifying children with urgency. […] The early detection of the disease during the asymptomatic phase is therefore paramount to increase the chances of a timely intervention and better clinical outcomes. […] As explained by Gaviglio, when considering these criteria and applying them to MLD, it is appropriate to say that the disease meets them all and should be included in newborn screening panels. This will help the early identification of patients with MLD while still in the asymptomatic phase, allowing for early access to potential disease-modifying treatments and improved health outcomes that would otherwise be negated, leading to irreversible neurodegeneration and early death of affected children.

• #40 A systematic review on the birth prevalence of metachromatic leukodystrophy | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-024-03044-w

  This review provides a foundation for further analysis of the regional epidemiology of MLD. […] It is typical to see birth prevalence ranges of 1.41.8 per 100,000 or 1 in 40,000 to 1 in 160,000 quoted in the literature; however, it is important to recognize regional and societal variations in the epidemiology of MLD that are biologically driven rather than a result of testing methodologies. […] The objective of this systematic review was to generate a qualitative synthesis of estimates of incidence, birth prevalence and prevalence of MLD in countries across the world, stratifying results by clinical subtype. […] The birth prevalence estimate by clinical subtype of MLD was highest for late-infantile cases in each of the three European studies reporting this breakdown. […] This systematic review highlights several data gaps that, if closed, could help to advance our understanding of the epidemiology of MLD.

• #41 A systematic review on the birth prevalence of metachromatic leukodystrophy | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-024-03044-w

  Further research is needed to document MLD cases worldwide and to improve our understanding of the distribution of MLD cases by disease severity. […] Findings from this systematic review and associated future work have practical relevance in informing local decisions on the implementation of NBS for MLD.

• #42 The natural history and burden of illness of metachromatic leukodystrophy: a systematic literature review | European Journal of Medical Research | Full Text

  https://eurjmedres.biomedcentral.com/articles/10.1186/s40001-024-01771-1

  Sweden was reported to have the highest incidence of MLD at 2.5 per 100,000 births, and Japan was reported to have the lowest incidence at 0.16 per 100,000 births. […] The percentage of MLD cases within leukodystrophies was reported in nine studies and ranged from 8.0% to 42.4%. […] The reported proportion of MLD within LSDs was reported in seven studies and ranged from 3.3% to 47.6%. […] Key knowledge gaps include data on mortality by clinical subtype, humanistic and economic outcomes, and differences between the early- and late-juvenile MLD subtypes. […] In addition to the knowledge gaps described earlier, there were also insufficient epidemiological data to compare incidence and prevalence by country or region, in part owing to varying methodology and study periods between publications.

• #43 The natural history and burden of illness of metachromatic leukodystrophy: a systematic literature review | European Journal of Medical Research | Full Text

  https://eurjmedres.biomedcentral.com/articles/10.1186/s40001-024-01771-1

  Sweden was reported to have the highest incidence of MLD at 2.5 per 100,000 births, and Japan was reported to have the lowest incidence at 0.16 per 100,000 births. […] The percentage of MLD cases within leukodystrophies was reported in nine studies and ranged from 8.0% to 42.4%. […] The reported proportion of MLD within LSDs was reported in seven studies and ranged from 3.3% to 47.6%. […] Key knowledge gaps include data on mortality by clinical subtype, humanistic and economic outcomes, and differences between the early- and late-juvenile MLD subtypes. […] In addition to the knowledge gaps described earlier, there were also insufficient epidemiological data to compare incidence and prevalence by country or region, in part owing to varying methodology and study periods between publications.

• #44 A systematic review on the birth prevalence of metachromatic leukodystrophy | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-024-03044-w

  Further research is needed to document MLD cases worldwide and to improve our understanding of the distribution of MLD cases by disease severity. […] Findings from this systematic review and associated future work have practical relevance in informing local decisions on the implementation of NBS for MLD.

• #45 Population Carrier Rates of Pathogenic ARSA Gene Mutations: Is Metachromatic Leukodystrophy Underdiagnosed? | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0020218

  Metachromatic leukodystrophy (MLD) is a severe neurometabolic disease caused mainly by deficiency of arylsulfatase A encoded by the ARSA gene. Based on epidemiological surveys the incidence of MLD per 100 000 live births varied from 0.6 to 2.5. […] Taking into account ARSA gene mutation distribution among 60 Polish patients, the expected MLD birth prevalence in the general population (assuming no selection against homozygous fetuses) was estimated as 4.0/100 000 and 4.1/100 000, respectively for the 1st and the 2nd cohort with a pooled estimate of 4.1/100 000 (CI: 1.89.4) which was higher than the estimate of 0.38 per 100 000 live births based on diagnosed cases. […] The observed discrepancy between the measured incidence of metachromatic leukodystrophy and the predicted carriage rates suggests that MLD is substantially underdiagnosed in the Polish population.

• #46 Population Carrier Rates of Pathogenic ARSA Gene Mutations: Is Metachromatic Leukodystrophy Underdiagnosed? | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0020218

  The expected prevalence of fetuses conceived with two pathogenic ARSA mutations in Poland (4.1 per 100 000) is substantially higher than the birth prevalence of MLD based on diagnosed cases (0.38 per 100 000 live births as determined by us or 0.53 per 100 000 (1 in 189 000) as previously reported in Poland). […] This discrepancy between our estimate and observed incidence of MLD in Poland may have several causes. […] One possible reason for the discrepancy between observed and expected prevalence of MLD may be related to disease underdiagnosis, especially among patients with p.I179S mutation.

• #47 Metachromatic leukodystrophy – Wikipedia

  https://en.wikipedia.org/wiki/Metachromatic_leukodystrophy

  The incidence of metachromatic leukodystrophy is estimated to occur in 1 in 40,000 to 1 in 160,000 individuals worldwide. […] There is a much higher incidence in certain genetically isolated populations, such as 1 in 75 in Habbanites (a small group of Jews who immigrated to Israel from southern Arabia), 1 in 2,500 in the western portion of the Navajo Nation, and 1 in 8,000 among Arab groups in Israel. […] As an autosomal recessive disease, 1 in 40,000 equates to a 1 in 100 carrier frequency in the general population. […] In the US, there are an estimated 3,600 MLD births per year, with 1,900 alive; in Europe 3,100, and worldwide 49,000 alive. […] MLD is considered a rare disease in the US and other countries.

• #48 Metachromatic leukodystrophy – Wikipedia

  https://en.wikipedia.org/wiki/Metachromatic_leukodystrophy

  The incidence of metachromatic leukodystrophy is estimated to occur in 1 in 40,000 to 1 in 160,000 individuals worldwide. […] There is a much higher incidence in certain genetically isolated populations, such as 1 in 75 in Habbanites (a small group of Jews who immigrated to Israel from southern Arabia), 1 in 2,500 in the western portion of the Navajo Nation, and 1 in 8,000 among Arab groups in Israel. […] As an autosomal recessive disease, 1 in 40,000 equates to a 1 in 100 carrier frequency in the general population. […] In the US, there are an estimated 3,600 MLD births per year, with 1,900 alive; in Europe 3,100, and worldwide 49,000 alive. […] MLD is considered a rare disease in the US and other countries.

• #49 FDA Approves First Gene Therapy for Children with Metachromatic Leukodystrophy | FDA

  https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-children-metachromatic-leukodystrophy

  Metachromatic leukodystrophy is a debilitating, rare genetic disease affecting the brain and nervous system. […] It is estimated that MLD affects one in every 40,000 individuals in the United States. […] MLD is a devastating disease that profoundly affects the quality of life of patients and their families. […] This approval represents important progress in the advancement and availability of effective treatments, including gene therapies, for rare diseases.

• #50 A systematic review on the birth prevalence of metachromatic leukodystrophy | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-024-03044-w

  This review provides a foundation for further analysis of the regional epidemiology of MLD. […] It is typical to see birth prevalence ranges of 1.41.8 per 100,000 or 1 in 40,000 to 1 in 160,000 quoted in the literature; however, it is important to recognize regional and societal variations in the epidemiology of MLD that are biologically driven rather than a result of testing methodologies. […] The objective of this systematic review was to generate a qualitative synthesis of estimates of incidence, birth prevalence and prevalence of MLD in countries across the world, stratifying results by clinical subtype. […] The birth prevalence estimate by clinical subtype of MLD was highest for late-infantile cases in each of the three European studies reporting this breakdown. […] This systematic review highlights several data gaps that, if closed, could help to advance our understanding of the epidemiology of MLD.

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