Late-infantile and juvenile Krabbe disease

Krabbe disease damages myelin, the fatty coating that protects nerves in the brain and body. Doctors group it by the age when symptoms start, and this page covers two later forms. Late-infantile disease starts between roughly 6 months and 3 years of age. Juvenile disease starts between about age 3 and the teenage years.

Experts have not always agreed on these age cut-offs. Newer US sources now draw the main line at 12 months. Symptoms that start before age 1 count as infantile Krabbe disease, and symptoms that start later count as later-onset disease. Children whose symptoms start after 12 months tend to have slower disease and do better after transplant. Krabbe disease can also begin in teenagers or adults, and people with these later forms may live many years after it starts.

Like the infantile form, it is caused by changes in the GALC gene, which carries the instructions for the enzyme galactocerebrosidase. Too little enzyme lets a toxic substance called psychosine build up and harm the cells that make myelin. Rarely, changes in a different gene, PSAP, cause a later-onset form.

Krabbe disease is inherited in an autosomal recessive way. A child is affected when both copies of the gene carry a change, one from each parent. Some gene changes are linked with later onset, but a gene result cannot yet reliably predict when symptoms will start or how fast they will progress. Brothers and sisters of an affected child can have the condition before showing symptoms, which is one reason families are offered testing.

In late-infantile disease, common first signs are losing skills, irritability, an unsteady walk, slow motor development and muscles that are too stiff or too floppy. A US study looked at 35 children whose disease began between 6 months and 3 years of age, seen from 2000 to 2017. In those with symptoms, the symptoms started at a median age of 11.5 months. Diagnosis came a median of 3.5 months later.

Juvenile and later forms often begin with trouble walking or with vision, and skills can be lost over time. How fast the disease moves varies widely. In a German study, walking problems were the first sign in all 8 people whose symptoms began after their first birthday, and progression differed a great deal from person to person.

US newborn screening is designed to find the infantile form. It can also flag babies who may develop a later form, but doctors cannot yet predict whether or when their symptoms will begin. US guidelines say follow-up for these babies is not as time-critical as for the infantile form. In New York, none of about 40 babies flagged this way had been reported to have worrying nerve symptoms after a median of 5 years, as of 2018.

Many families wait months between the first signs and a diagnosis, because early signs such as irritability or an unsteady walk can have many causes. By the time the cause is found, a child may already have lost some skills.

Deciding about transplant is hard when a child has already started to change. Families weigh the risks of chemotherapy and transplant against a benefit that is less certain than in babies treated before symptoms. The answer can differ from one child to the next, and some families decide against transplant.

Whatever the choice, most children need long-term therapy, equipment and school support. Parents often coordinate care across neurology, rehabilitation and other specialists while caring for the rest of the family.

When a transplant is chosen, the blood-forming stem cells come from another person. That can be a matched brother or sister who does not have Krabbe disease, a matched unrelated volunteer, or donated umbilical cord blood. The transplant team chooses the source for each child.

Brothers and sisters are tested for Krabbe disease before they are considered as donors. A sibling found to have it before symptoms may be a candidate for early treatment themselves. When they can, teams also avoid donors who carry a Krabbe gene change.

For this group, transplant is a careful team decision rather than an automatic next step, and the evidence is still limited. When a transplant is chosen, a larger and more diverse registry gives the team more possible donors to search.