Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant (ADLD)

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MedlinePlus Genetics: ⁴² Autosomal dominant leukodystrophy with autonomic disease (ADLD) is one of a group of genetic disorders called leukodystrophies. Leukodystrophies are characterized by abnormalities of the nervous system's white matter, which consists of nerve fibers covered by a fatty substance called myelin. Myelin insulates and protects nerve fibers and promotes the rapid transmission of nerve impulses.People with ADLD develop signs and symptoms of the condition in adulthood, typically in their forties or fifties. The first signs of the condition often involve problems with the autonomic nervous system, which controls involuntary body processes such as the regulation of blood pressure and body temperature. These problems include difficulty with bowel and bladder function, a sharp drop in blood pressure upon standing (orthostatic hypotension), and erectile dysfunction in men. Rarely, people experience an inability to sweat (anhidrosis), which can lead to a dangerously high body temperature.In ADLD, movement difficulties often develop after the autonomic nervous system problems. Affected individuals can have muscle stiffness (spasticity) or weakness and involuntary rhythmic shaking, called intention tremor because it worsens during movement. People with ADLD often have difficulty coordinating movements (ataxia), including movements that involve judging distance or scale (dysmetria), such as picking up a distant object, and rapidly alternating movements (dysdiadochokinesis), including hand clapping or foot stomping. These movement problems usually first affect the legs, but as the condition worsens, the arms and eventually the face become involved. In some people with ADLD, the symptoms worsen during episodes of fever, infection, or exposure to heat. Due to difficulty walking and an unsteady gait, many affected individuals need a cane, walker, or wheelchair for assistance.Intelligence is usually unaffected; however, people who have had ADLD for a long time may have a decline in intellectual function (dementia). ADLD worsens slowly, and affected individuals usually survive 10 to 20 years after the onset of symptoms.

MalaCards based summary: Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant, also known as adult-onset autosomal dominant demyelinating leukodystrophy, is related to lmnb1-related autosomal dominant leukodystrophy and leukodystrophy, and has symptoms including personality changes, muscle spasticity and cerebellar ataxia. An important gene associated with Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant is LMNB1 (Lamin B1), and among its related pathways/superpathways are DREAM Repression and Dynorphin Expression and Cytoskeletal Signaling. Affiliated tissues include eye, spinal cord and cerebellum, and related phenotypes are muscle weakness and gait ataxia

OMIM®: ⁵⁷ Autosomal dominant adult-onset demyelinating leukodystrophy is a slowly progressive and fatal disorder that presents in the fourth or fifth decade of life and is characterized clinically by early autonomic abnormalities, pyramidal and cerebellar dysfunction, and symmetric demyelination of the CNS. ADLD differs from multiple sclerosis and other demyelinating disorders in that neuropathology shows preservation of oligodendroglia in the presence of subtotal demyelination and lack of astrogliosis (summary by Padiath et al., 2006). Characteristic MRI findings include T2-weighted hyperintense changes in the upper corticospinal tract and cerebellar peduncles, with later development of confluent white matter changes in the frontoparietal area with relative sparing of the periventricular white matter (summary by Schuster et al., 2011). (169500) (Updated 08-Dec-2022)

UniProtKB/Swiss-Prot: ⁷³ A slowly progressive and fatal demyelinating leukodystrophy, presenting in the fourth or fifth decade of life. Clinically characterized by early autonomic abnormalities, pyramidal and cerebellar dysfunction, and symmetric demyelination of the CNS. It differs from multiple sclerosis and other demyelinating disorders in that neuropathology shows preservation of oligodendroglia in the presence of subtotal demyelination and lack of astrogliosis.

Disease Ontology: ¹¹ A leukodystrophy characterized by onset in the 4th or 5th decade of life of autonomic abnormalities, pyramidal and cerebellar dysfunction, and symmetric demyelination of the CNS that has material basis in heterozygous tandem genomic duplication resulting in an extra copy of the LMNB1 gene on chromosome 5q.

GARD: ¹⁹ A rare, slowly progressive neurological disorder involving central nervous system demyelination, leading to autonomic dysfunction, ataxia and mild cognitive impairment.

Orphanet: ⁵⁸ A rare, slowly progressive neurological disorder involving central nervous system demyelination, leading to autonomic dysfunction, ataxia and mild cognitive impairment.

Wikipedia: ⁷⁵ Autosomal dominant leukodystrophy with autonomic disease is a rare neurological condition of genetic... more...

Clinical features from OMIM®:

Search NIH Clinical Center for Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant