WHAT IS ADLD?
Autosomal Dominant Leukodystrophy (ADLD) is a genetic disorder that develop symptoms in the fourth or fifth decade due to nerve damage that slowly progresses. The onset often includes bowel or bladder dysfunction, male impotence, loss of fine motor skills, and the type of blood pressure problem (orthostatic hypotension) that makes you feel dizzy when you suddenly stand up. Later symptoms include difficulties using and controlling legs and arms, eventually leading to paralysis and problems swallowing. Intellectual impairment usually does not develop until a very late stage. ADLD is a fatal disorder, but it is slowly progressive; patients often survive for several decades.
ADLD is an autosomal dominant genetic disorder, which means that each child from a parent with ADLD has a 50% chance of developing ADLD as well. Although ADLD is very rare, with an estimated frequency of one in a million, ADLD patients have been reported in countries in the Americas, Europe, and Asia. The defects differ between many families, indicating that they arose independently.
ADLD is caused by mutations of the gene LMNB1 that encodes for the protein Lamin B. Lamin B is a protein that is present in every cell in the body and plays an essential role in various processes. The genetic defects in the LMNB1 gene result in levels of Lamin B protein that are too high. Although Lamin B is present in all cells in the body, high levels of Lamin B mainly cause problems in the brain. In the brain these high levels result in the loss of the protective layer (the myelin sheet) around the nerves. Without this layer, the nerves get damaged.
Diagnosis
When clinical symptoms and MRI findings suggest ADLD, a genetic test is performed to make a final diagnosis.
TREATMENT
There is currently no cure for ADLD. Treatment consists of the management of symptoms. The below list of management options are based on a review focusing on clinical symptoms, management and diagnosis (Nahhas, Sabet Rasekh, Vanderver, & Padiath, 2016):
- Neurogenic bladder may require management of urinary retention and/or urgency and recurrent urinary tract infection.
- Constipation may require good hydration, increased dietary fiber, stool softeners, and/or laxatives.
- Hypotensive events can be minimized by pharmacologic intervention, physical therapy, and increased dietary salt.
- Feeding difficulties can be managed with speech therapy and appropriate feeding interventions to assure adequate nutrition while preventing aspiration pneumonia.
- Spasticity may be treated with medications and physical therapy.
- Ataxia can be managed with strategies to minimize falls and increase strength, and adaptive equipment such as walkers or wheelchairs.