Guidance for primary care clinicians diagnosing and managing children with leukodystrophies

The leukodystrophies are a group of more than 400 genetic conditions in which the brain's white matter is abnormal due to altered development, decreased amount, or degeneration of the lipid insulation covering neuronal processes in the brain.

Consider a leukodystrophy in any child with developmental delay, global regression, or stops meeting developmental milestones. The diagnosis of a leukodystrophy requires an MRI and biochemical and/or genetic testing; there are no pathognomonic clinical findings. Vigilance for potential complications (growth problems, feeding problems, spasticity, and seizures) permits early intervention. Diagnosis is important and potentially urgent because effective treatments are available within a time-sensitive window.

Other Names

Delay or regression in multiple abilities
Children with leukodystrophy may have delays in their development or may regress in some combination of language, interaction, motor, fine motor, and visual abilities.

Myelin varies by age
Because the appearance of myelin in children of different ages varies, MRIs should be performed in a facility where pediatric neuroradiologists are available to interpret the scans.

Swallowing issues may become a problem
Swallowing difficulty may lead to long feeding times, weight loss, and aspiration pneumonias. If suspected, swallowing difficulty should be evaluated by periodic swallow studies. Treatment consists of alternative feeding approaches, such as a gastrostomy tube. See Feeding Tubes & Gastrostomies in Children.

Poor weight gain
Swallowing difficulty may lead to long feeding times, weight loss, and aspiration pneumonias. If suspected, swallowing difficulty should be evaluated by periodic swallow studies. Treatment consists of alternative feeding approaches, such as a gastrostomy tube. See Boosting Calories for Babies, Toddlers, and Older Children.

Development (Cognitive, Motor, Language, Social-Emotional)
Collaborate with teachers and school personnel to advocate for services such as an IEP and 504 Plan. School Accommodations: IEPs & 504s provides ideas for facilitating this type of communication.

Presentations

Diagnostic Criteria and Classifications

Diagnostic Testing & Screening

Genetics

Incidence & Prevalence

Differential Diagnosis

Comorbid Conditions

Some leukodystrophies present with impairment from birth and do not progress, while others have progressive deterioration in neurologic function. In general, leukodystrophies are severe diseases. In a large cohort, only 51% of children walked and 28% achieved the ability to track visually. [Bonkowsky: 2010] In a few leukodystrophies, hematopoietic stem cell transplantation (bone marrow transplantation) can prevent primary disease manifestations if performed early in the disease course. [Pagon: 2014]

When a leukodystrophy is identified, the possibility of an existing treatment should be considered with the child’s geneticist/neurologist. There are multiple existing treatments, and more are expected in the near future. Some treatments only work in pre-symptomatic or early symptomatic stages, so rapid diagnosis is important.

Next, existing abilities should be evaluated, and rehabilitation should be provided to help regain function or to prevent further deterioration as much as possible. Psychiatric symptoms may be the first to present in older children, adolescents, and adults. Seizures may occur as presenting or early symptoms. Endocrine abnormalities (hypothyroidism, diabetes, and others) are also observed and should be looked for on diagnosis. Spasticity may limit movement and cause pain in some children and should be monitored for over time.

Neurology

Dental

The benefit of subspecialist involvement may increase as the child becomes progressively more affected. Balance the benefit of subspecialty help with the family's wishes and convenience of services. Coordination of care among subspecialists, therapists, school, and community services will help optimize outcomes, minimize duplication of services, and ensure the family's goals are addressed. The medical home clinician may need to be involved with the individual education plan (IEP) to ensure the child receives needed school services. A teacher coming to the home to work with the child may be helpful in some cases.

Pediatric Neurology (see NW providers [0])
Involve in the diagnosis and periodic assessments. Consider referral for monitoring developmental progress. Depending on the frequency of seizures and the response to medications, consider consultative or co-management care. Neurologists can also monitor neurological changes and suggest or manage interventions.

Medical Genetics (see NW providers [1])
Consider for specific genetic diagnosis.

Pediatric Ophthalmology (see NW providers [1])
Consider involving to diagnose certain forms of leukodystrophy.

Developmental - Behavioral Pediatrics (see NW providers [1])
Refer for help monitoring developmental progress and academic achievement and suggesting or coordinating interventions when necessary.

Pediatric Ophthalmology (see NW providers [1])
Consider involving to diagnose certain forms of leukodystrophy.

Pediatric Physical Medicine & Rehabilitation (see NW providers [3])
Consider for help in managing spasticity, impairments in walking, and the activities of daily living.

Pediatric Dentistry (see NW providers [2])
Refer to monitor dental health and treat as necessary. Some issues that affect dental care are problems handling saliva, reflux, mouths that do not open well, and the need for sedation for cleaning and other procedures.

CSHCN Clinics (see NW providers [2])
In some locales, children may be able to receive care from a specialty clinic.