Krabbe disease (globoid cell leukodystrophy)

Krabbe disease belongs to a group of conditions called leukodystrophies, in which the white matter of the nervous system loses its myelin. Myelin is the spongy, insulating covering of nerve fibres that speeds the transmission of signals. The GALC gene makes an enzyme, galactosylceramidase, that breaks down certain fats called galactolipids. When the enzyme is missing, these fats accumulate and form large cells with several nuclei, called globoid cells, and a related toxic substance, psychosine, damages the cells that make myelin.

Metabolic Support UK estimates the disorder affects approximately 1 in 100,000 in the Northern European population. Higher rates are reported in a few isolated communities in Israel.

In the infantile form, babies usually seem well for the first weeks and then become irritable. Early signs include feeding difficulties, stiff posture, low or changing muscle tone and episodes of fever with no sign of infection. Vision and hearing loss and seizures follow, and mental and physical development is delayed. Progressive muscle weakness makes moving, chewing, swallowing and breathing harder. The condition is severe, and those affected rarely live beyond the age of 2.

Because early signs resemble colic, reflux or common infections, diagnosis can be delayed. A baby with unexplained persistent irritability, stiffness and developmental slowing, especially with a family history, needs a prompt paediatric neurology opinion.

Less often, Krabbe disease begins in later childhood, adolescence or adulthood. Walking difficulties and vision problems are the most common first symptoms, but they vary widely between people. Seizures and loss of thinking skills can occur. People with late-onset disease can survive many years after symptoms begin, which can make the diagnosis harder to reach when the picture looks like another neurological condition. MRI of the brain and spine, enzyme testing and genetic analysis help to separate it from other leukodystrophies.

Doctors combine symptoms, family history and several investigations: blood and urine tests, electrophysiology including an electroencephalogram, and brain MRI. Genetic testing and enzyme assays confirm the diagnosis. In families where a child has already had Krabbe disease, testing a later baby can be planned before symptoms start, which matters for the transplant option below.

Krabbe disease is not part of the routine NHS newborn blood spot test in England, so diagnosis relies on clinical suspicion or family testing. Krabbe UK, a charity formerly known as Save Babies Through Screening Foundation UK, campaigns about newborn screening and supports families.

There is no known cure. Haematopoietic stem cell transplantation has been shown to benefit cases early in the course of the disease. Cord blood transplants from unrelated donors have been successful in stopping the disease when given before obvious symptoms appear, according to Metabolic Support UK.

Most treatment is symptomatic and supportive. Physiotherapy can maintain muscle tone and circulation, and teams manage irritability, feeding, seizures, reflux, chest infections and pain. Palliative care can run alongside active treatment from diagnosis, to support the child and family whatever the stage.

Alex, The Leukodystrophy Charity, provides support for people with any genetic leukodystrophy and is recognised as a centre of excellence for adrenoleukodystrophy. Krabbe UK offers practical support and advice to families and champions research. Metabolic Support UK explains the condition in plain language and links families to genetic counselling.

Genetic counselling is offered after a diagnosis to explain how the condition was inherited and what the risk is for future pregnancies and relatives. Nothing the parents did could have prevented the condition.

Krabbe disease is autosomal recessive. Each parent carries one working and one non-working copy of the gene and is healthy. When both parents are carriers there is a 25% chance of an affected baby in each pregnancy, a 50% chance of a carrier and a 25% chance of a baby who is neither affected nor a carrier.

Call 999 for a seizure that does not stop, difficulty breathing, or choking. Seek urgent medical advice for a baby who is persistently irritable, feeding poorly, unusually stiff or floppy, or has a fever without an obvious cause, and mention any family history of a neurological condition.