Krabbe disease, also known as globoid cell leukodystrophy (GLD), is a rare autosomal recessive disease, which means both copies of the affected gene in each cell have mutations.
The parents of an individual with this disease usually each carry one copy of the mutated gene, but do not show signs and symptoms of the condition. The affected gene is called GALC, which provides instructions for producing an enzyme called galactocerebrosidase. Deficiency of this enzyme leads to accumulation of a highly toxic fat, known as psychosine, in the central nervous system and in the peripheral nerves.
The early infantile form of the disease is the most common. Children appear normal during the first few months after birth, but become hyperirritable and hypersensitive to auditory stimuli and even to touch, and experience some stiffness of limbs. Slight regression of psychomotor development, and feeding difficulties and vomiting may be observed. Then, there is rapid deterioration with marked hypertonicity, with extended and crossed legs, flexed arms, and arched back, eventually resulting in a ‘burned out” stage, sometimes reached within a few weeks or months. Infants become blind and have no contact with their surroundings. Patients rarely survive for more than 2 years.
Juvenile and adult-onset cases are well documented. The juvenile cases have been subdivided into late infantile/early childhood onset (6 months - 3 years), and late childhood onset (3 - 8 years). The early childhood form progresses rapidly, with death approximately two years after onset. The late childhood forms present with loss of vision, stiffness and paralysis, and intellectual regression leading to death within 10 months to seven years after onset of initial symptoms. The number of reports of adult-onset cases is increasing, with progressive stiffness mostly in the lower extremities often wrongly diagnosed as multiple sclerosis.
Studies have shown that transplantation of cord blood hematopoietic stem cells have a beneficial effect if performed in infants prior to developing any symptoms. Newborn screening is being conducted in several states to identify cases at birth before the presentation of symptoms. Gene therapy is currently under investigation in Europe.