What is Krabbe's Disease (also known as Globoid Cell Leukodystrophy)?

From the Guidelines

Hematopoietic stem cell transplantation is the only treatment available for patients with Krabbe disease and is shown to be effective, particularly if performed before symptoms appear. Krabbe disease, also known as globoid cell leukodystrophy, is an autosomal recessive lysosomal disease caused by a deficiency in galactocerebrosidase (GALC) activity, leading to rapid neurodegeneration and early death in its infantile-onset form 1. The disease can be divided into four subtypes based on the age of onset and clinical presentation, with the majority of patients developing the infantile-onset form. Patients with the late-onset type exhibit ataxia, weakness, vision loss, and psychomotor regression. Key aspects of Krabbe disease management include:

• Early diagnosis through newborn screening, which is crucial for effective treatment
• Hematopoietic stem cell transplantation as the primary treatment approach
• Supportive care, including physical therapy, anti-seizure medications, and nutritional support, to manage symptoms and improve quality of life. The estimated frequency of Krabbe disease is 1 in 400,000, and it is caused by homozygous or compound heterozygous pathogenic variants in the galactocerebrosidase gene (HGNC: 4115) 1.

From the Research

Overview of Krabbe Disease

• Krabbe disease is a rare neurodegenerative disorder caused by mutations in the gene encoding the galactocerebrosidase enzyme 2.
• The disease is characterized by demyelination of the central and peripheral nervous systems, leading to progressive neurodegeneration and reduced quality of life 3.
• Krabbe disease can be classified into different subtypes, including early-infantile, late-infantile, and later-onset types, with varying degrees of severity and progression 2, 4.

Symptoms and Diagnosis

• Common initial symptoms of Krabbe disease include irritability, feeding difficulties, appendicular spasticity, and developmental delay 3.
• Other prevalent symptoms include axial hypotonia, abnormal deep tendon reflexes, constipation, abnormal pupillary response, scoliosis, loss of head control, and dysautonomia 3.
• Diagnosis can be made by measuring galactocerebrosidase activity in leukocytes and cultured cells, as well as through newborn screening programs 5.

Treatment and Management

• The only disease-modifying treatment currently available is hematopoietic stem cell transplantation (HSCT), which is effective only when performed early in the course of the disease 2, 4.
• HSCT can improve lifespan and functional abilities in patients with Krabbe disease, particularly those who undergo transplantation before onset of symptoms 4, 6.
• Symptomatic treatment and supportive care can also improve the quality of life of patients and their families 2.
• Research is ongoing to develop new treatments, including combination therapies such as bone marrow transplantation with intra-venous gene therapy 5.

Prognosis and Outcomes

• The median survival for patients with early-onset Krabbe disease is approximately 2 years 3.
• Patients who undergo HSCT can have improved cognitive and language function, as well as gross and fine motor development, although outcomes can vary widely 4, 6.
• Early diagnosis and treatment are critical to improving outcomes for patients with Krabbe disease 5.