Leukoencephalopathy, Hereditary Diffuse, with Spheroids 1 (HDLS1)

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MedlinePlus Genetics: ⁴² Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a neurological condition characterized by changes to certain areas of the brain. A hallmark of ALSP is leukoencephalopathy, which is the alteration of a type of brain tissue called white matter. White matter consists of nerve fibers (axons) covered by a substance called myelin that insulates and protects them. The axons extend from nerve cells (neurons) and transmit nerve impulses throughout the body. Areas of damage to this brain tissue (white matter lesions) can be seen with magnetic resonance imaging (MRI). Another feature of ALSP is swellings called spheroids in the axons of the brain, which are a sign of axon damage. Also common in ALSP are abnormally pigmented glial cells. Glial cells are specialized brain cells that protect and maintain neurons. Damage to myelin and neurons is thought to contribute to many of the neurological signs and symptoms in people with ALSP.Symptoms of ALSP usually begin in a person's forties and worsen over time. Personality changes, including depression and a loss of social inhibitions, are among the earliest symptoms of ALSP. Affected individuals may develop memory loss and loss of executive function, which is the ability to plan and implement actions and develop problem-solving strategies. Loss of this function impairs skills such as impulse control, self-monitoring, and focusing attention appropriately. Some people with ALSP have mild seizures, usually only when the condition begins. As ALSP progresses, it causes a severe decline in thinking and reasoning abilities (dementia).Over time, motor skills are affected, and people with ALSP may have difficulty walking. Many develop a pattern of movement abnormalities known as parkinsonism, which includes unusually slow movement (bradykinesia), involuntary trembling (tremor), and muscle stiffness (rigidity). The pattern of cognitive and motor problems are variable, even among individuals in the same family, although almost all affected individuals ultimately become unable to walk, speak, and care for themselves.ALSP was previously thought to be two separate conditions, hereditary diffuse leukoencephalopathy with spheroids (HDLS) and familial pigmentary orthochromatic leukodystrophy (POLD), both of which cause very similar white matter damage and cognitive and movement problems. POLD was thought to be distinguished by the presence of pigmented glial cells and an absence of spheroids; however, people with HDLS can have pigmented cells, too, and people with POLD can have spheroids. HDLS and POLD are now considered to be part of the same disease spectrum, which researchers have recommended calling ALSP.

MalaCards based summary: Leukoencephalopathy, Hereditary Diffuse, with Spheroids 1, also known as hereditary diffuse leukoencephalopathy with spheroids, is related to leukoencephalopathy with vanishing white matter and pick disease of brain, and has symptoms including bradykinesia, memory loss and muscle rigidity. An important gene associated with Leukoencephalopathy, Hereditary Diffuse, with Spheroids 1 is CSF1R (Colony Stimulating Factor 1 Receptor), and among its related pathways/superpathways are Hematopoietic Stem Cells and Lineage-specific Markers and Dendritic Cells Developmental Lineage Pathway. The drugs Busulfan and Rituximab have been mentioned in the context of this disorder. Affiliated tissues include brain, endothelial and heart, and related phenotypes are seizure and dysarthria

GARD: ¹⁹ Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is a neurological condition characterized by changes to certain areas of the brain. A hallmark of HDLS is leukoencephalopathy, which is damage to a type of brain tissue called white matter. Another common finding is axon damage due to swellings called spheroids. Damage to myelin and axons is thought to contribute to many of the neurological signs and symptoms seen in people with this condition, including the personality changes, loss of memory, changes in motor skills and dementia. HDLS is caused by genetic changes in the CSF1R gene. It is inherited in an autosomal dominant pattern.

OMIM®: ⁵⁷ Hereditary diffuse leukoencephalopathy with spheroids-1 (HDLS1) is an autosomal dominant adult-onset rapidly progressive neurodegenerative disorder characterized by variable behavioral, cognitive, and motor changes. Patients often die of dementia within 6 years of onset. Brain imaging shows patchy abnormalities in the cerebral white matter, predominantly affecting the frontal and parietal lobes (summary by Rademakers et al., 2012). (221820) (Updated 08-Dec-2022)

UniProtKB/Swiss-Prot: ⁷³ An autosomal dominant adult-onset rapidly progressive neurodegenerative disorder characterized by variable behavioral, cognitive, and motor changes. Patients often die of dementia within 6 years of onset. Brain imaging shows patchy abnormalities in the cerebral white matter, predominantly affecting the frontal and parietal lobes.

Orphanet: ⁵⁸ Hereditary diffuse leukoencephalopathy with axonal spheroids and pigmented glia is a rare autosomal dominant disease characterized by a complex phenotype including progressive dementia, apraxia, apathy, impaired balance, parkinsonism, spasticity and epilepsy.

Disease Ontology: ¹¹ A leukodystrophy that is characterized by progressive dementia, apraxia, apathy, impaired balance, parkinsonism, spasticity and epilepsy and has material basis in heterozygous mutation in the CSF1R gene on chromosome 5q32.

Wikipedia: ⁷⁵ Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is a rare adult onset autosomal dominant... more...

Clinical features from OMIM®:

Search NIH Clinical Center for Leukoencephalopathy, Hereditary Diffuse, with Spheroids 1