What's Krabbe disease?
Krabbe disease (also called globoid cell leukodystrophy) is an inherited lysosomal disorder that results from deficiency of the enzyme galactosylceramidase (GALC). Without enough GALC, a toxic substance called psychosine builds up and progressively strips myelin from nerves in both the brain and the peripheral nerves, leading to neurodegeneration. It follows an autosomal recessive inheritance pattern and most often begins in infancy. This entry confirms GALC as the principal gene.
| Also indexed as | ORPHA:487, MONDO:0009499 |
|---|---|
| Features mapped | 17 |
| Treatments mapped | 3 |
| Published sources | 12 |
| Last reviewed | 2026-08-04 |
Signs and symptoms
Reduced tissue galactocerebrosidase activity
in krabbe disease the activity of the lysosomal enzyme galactosylceramidase (GALC) is deficient; this enzyme shortfall is the characterizing feature of the disorder, which is also called globoid cell leukodystrophy.
Childhood onset
the particular combination of GALC gene changes a person inherits determines the type of krabbe disease they will have, ranging from infantile to later-onset forms.
Infantile onset
build-up of psychosine is thought to be the main cause of the nerve-coating loss, nerve-cell degeneration, and nerve inflammation that characterize the early infantile form of krabbe disease, which has a median survival of about 1.5 to 2 years.
Peripheral demyelination
Loss of myelin affects nerves in both the central nervous system and the peripheral nerves, which is what drives the progressive neurological decline.
Diffuse cerebral atrophy
krabbe disease is a rare inherited lysosomal storage disorder characterized by severe loss of myelin (the protective nerve coating) affecting both the central and peripheral nervous systems.
Motor deterioration
the features of krabbe disease progress through stages: it often starts with irritability, stiffness, and feeding difficulties, then jerking movements of the arms and legs and increased muscle tone, and eventually severe loss of muscle tone and of movement.
Decreased nerve conduction velocity
nerve-conduction testing in krabbe disease has shown severe sensory and motor polyneuropathy of both demyelinating and axonal types.
Neurodegeneration
the enzyme deficiency in krabbe disease leads to toxic build-up of a substance called psychosine, which results in progressive loss of the myelin covering of nerves and in death of nerve cells.
Sensorimotor neuropathy
nerve-conduction testing in newborn-screened krabbe disease has shown severe sensory and motor polyneuropathy of mixed demyelinating and axonal types.
CNS demyelination
in krabbe disease the GALC enzyme is needed to break down galactosylceramide, an important building block of myelin, the protective coating around nerves.
Autosomal recessive inheritance
Krabbe disease is inherited in an autosomal recessive pattern: both inherited copies of GALC must carry disease variants for a child to be affected, and single-variant carriers are typically unaffected.
Hypertonia
Increased muscle tone (hypertonicity) is common in the early stages, later giving way to severe low tone (hypotonia).
Hypotonia
Krabbe disease follows a stepwise course: after an early phase of stiffness and rigidity, children eventually become severely floppy (hypotonia) with loss of movement as the disease advances. The shift from stiffness to floppiness is part of the late stage.
Irritability
Early infantile disease often begins with marked irritability, along with stiffness and feeding problems.
Generalized myoclonic seizure
As Krabbe disease progresses, babies often develop sudden muscle jerks (myoclonic jerks) of the arms and legs. These come from the damage the disease does to the nervous system and are part of its characteristic stepwise course.
Peripheral neuropathy
Nerve testing shows a sensory-motor polyneuropathy, reflecting damage to the peripheral nerves alongside the central disease.
Feeding difficulties
Feeding difficulties appear early and contribute to poor growth as the disease progresses.
How it is diagnosed
Krabbe disease
Diagnosed using: galactosylceramidase (GALC) enzyme activity assay.
“Low GALC activity in this screening test may indicate a diagnosis of Krabbe disease.”
Krabbe disease
Diagnosed using: GALC enzyme activity and GALC variant testing.
“Symmetrical white matter changes in the pyramidal tract and optic radiation on MRI, absence of GALC enzyme activity in the blood, and identification of a pathogenic and likely pathogenic GALC variants confirmed the diagnosis of late-onset KD.”
Treatment and management
What the research describes, not a recommendation. Treatment decisions belong with your clinician.
This covers treatments that appear in the published research mapped here. Investigational and experimental therapies are not included, so their absence is a boundary of this map, not a sign they do not exist.
hematopoietic stem cell transplantation
Hematopoietic stem cell transplantation is the main established treatment; it can change the disease course and improve survival, but mainly when carried out before symptoms appear (often via newborn screening), because donor-derived cells supply the missing enzyme.
Used to help with: Krabbe disease.
“Hematopoietic stem cell transplantation (HSCT) is the only available…”
presymptomatic hematopoietic stem cell transplantation
the infantile form of krabbe disease can be treated at a presymptomatic stage with human stem cell transplantation, which improves survival and clinical outcomes.
Used to help with: Krabbe disease.
“Patients with the infantile form of Krabbe disease can be treated at a presymptomatic stage with human stem cell transplantation which improves survival and clinical outcomes.”
hematopoietic stem cell transplantation (standard of care)
the standard of care for krabbe disease is haematopoietic stem cell transplantation, which improves lifespan only when it is performed before symptoms appear.
Used to help with: Krabbe disease.
“…the standard of care of KD is haematopoietic stem cell transplantation which, however, improves the lifespan of Krabbe patients only when performed before symptoms appear.”
How to read the evidence labels
Where this comes from
This guide is built from 12 published source(s). Every claim above links back to one of them. Click any source ID to read the original on PubMed.
Take it further
Printed, source-linked documents built from this condition's graph — ready to bring to an appointment or attach to a coverage request. Every claim carries its published source, the same as this guide.