Krabbe Disease Treatment & Management

Updated: Dec 18, 2019
  • Author: Anna V Blenda, PhD; Chief Editor: Luis O Rohena, MD, MS, FAAP, FACMG  more...
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Treatment

Medical Care

Following the emergence of hematopoietic stem cell transplantation (HSCT) as a potential treatment for Krabbe disease, newborn screening has been implemented in New York State with additional states scheduled to follow suit. Numerous studies in human and animal models have shown varying degrees of benefit with HSCT, with greatest benefit occurring in patients who are asymptomatic or mildly symptomatic and when transplanted within the 1st month of life. [61, 63, 38, 64]

HCST should be considered in individuals with late-onset or slowly progressive Krabbe disease and in individuals with infantile-onset disease, in the early neonatal asymptomatic period. Short-term benefits with HSCT are reported in the medical literature, including a suggestion of delayed progression and improved survival; however, transplantation mortality rates are 15%.

Data on long-term posttransplant neurocognitive and survival outcomes are accumulating. [64] Positive long-term effects of HSCT in presymptomatic infants includes an apparent increase in length of survival, improvements in quality of life versus those that are not transplanted, and an attenuated degree of neurologic complications, with some retaining normal receptive language skills and developing ambulation (although usually requiring assistive devices).

Limitations of HSCT include the persistent development of neurologic deficits, most of which are progressive in nature, including microcephaly, spasticity, growth restriction, and developmental delay (both verbal and motor) with regression. Ultimately, lack of curative effect is associated with HSCT. [63]

Considering the amount of interest and data on HSCT treatment for Krabbe disease, the Hunter's Hope Leukodystrophy Care Network developed standardized high-quality clinical practice guidelines for the care of pediatric patients (including those with Krabbe disease) undergoing treatment with HSCT. [65] They include the following considerations:

  • Donor selection
  • Guidelines for determining HSCT candidacy for patients with early infantile Krabbe disease
  • Special considerations for newborns undergoing HSCT
  • Supportive care during HSCT

Symptomatic treatment for some neurologic sequelae is available but has no significant effect on the clinical course.

Research continues into treatments targeting inflammatory markers, [66] enzyme replacement therapy, gene therapy, [67] and neural stem cell transplantation, although this has not yet advanced to the point of clinical trials.

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Consultations

The following consultations are indicated:

  • Clinical geneticist - For initial evaluation and diagnosis, for counseling families regarding recurrence risk, and to help provide prenatal testing if desired in future pregnancies
  • Neurologist - For symptomatic therapy and documentation of the multiple neurologic sequelae
  • Ophthalmologist
  • Audiologist
  • Social worker
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Diet

No known dietary modifications significantly alter the clinical course of Krabbe disease. Infants may ultimately require tube feedings for adequate energy intake; however, nutritional support does not change the disease course; therefore, some families may choose to forgo invasive alimentation methods.

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Activity

Neurologic sequelae may preclude adequate physical activity. Patients may benefit from physical and occupational therapy.

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Prevention

Provide genetic counseling for at-risk couples to explain reproductive options. Prenatal diagnosis, if feasible and desired, can be beneficial in future pregnancies by providing reassurance in the case of an unaffected fetus or by allowing an informed exploration of options, such as termination of pregnancy or, potentially, early stem cell therapy, in the case of an affected fetus.

If molecular testing in a patient with Krabbe disease identifies the causative mutations, family members at risk for carrying the mutation may wish to be tested. The mode of inheritance for Krabbe disease is autosomal recessive. Therefore, two causative mutations in the GALC gene result in disease. The parents of an affected child are obligate carriers. Each subsequent child of this couple has a 25% risk of also being affected. There is a 50% risk that a child of this couple is unaffected but a carrier. There is a 25% chance that another child of this couple will be unaffected and not a carrier. Each sibling of this couple may be carriers and may desire to know this information to determine the risk posed to their future children. Thus, genetic counseling is an important and integral component to the workup of a child with Krabbe disease.

Prenatal testing is best discussed prior to pregnancy. Options, including preimplantation genetic diagnosis to prenatal diagnosis, can be discussed at length with the family so that they can make the best decision for themselves.

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Long-Term Monitoring

Treatment of symptomatic individuals with infantile-onset Krabbe disease who are already at stage 2 or 3 is limited to supportive care.

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Further Inpatient Care

Hematopoietic stem cell transplantation (HSCT) in patients with Krabbe disease should be considered only at an experienced center and follow-up care coordinated with the transplant team.

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