Globoid cell leukodystrophy, also known as Krabbe disease, is a condition that affects the nervous system. This inherited disorder impairs the protective coating of the nerves cells known as myelin that is present throughout the nervous system and the brain. Commonly, the symptoms associated with this disorder begin before 6 months of age and as the disease progresses, death occurs by age 2. This disorder is estimated to affect around 1 in 100,000 individuals in the United States.
Causes
A genetic mutation in the GALC is identified to cause this disorder. The genetic mutation results in the deficiency of a certain enzyme called galactosylceramidase which impairs the normal growth and the maintenance of myelin important for the transmission of nerve impulses. Without the presence of myelin, the nerves of the brain and other parts of the body cannot function normally resulting in the symptoms associated with this condition. The inheritance pattern is an autosomal recessive manner meaning both the copies of the gene in each cell are defective. The parents of the affected individual each carry a single copy of the defective gene but don’t necessarily exhibit any symptoms associated with this disorder.
Symptoms
The symptoms of this disease can occur at any age. Infants with the early-onset can develop symptoms in the first six months of life while the late-onset may not develop any features of this disease until later in childhood, adolescence or adulthood. It is estimated that most commonly the affected individuals present the infantile form. The symptoms of the infantile form include irritability, vision loss, failure to thrive, feeding difficulties, developmental delay, muscle weakness, sensitivity to light, peripheral neuropathy, seizures, fevers and hearing loss. Less commonly, the late-onset can present visual problems and walking difficulties which are the most common features, although the symptoms can vary greatly among the affected cases.
Diagnosis
A physical examination and an evaluation of the symptoms can indicate a neurological disease. A blood test and skin biopsy may be required to determine the activity of the enzyme galactosylceramidase and the absence or low activity of this enzyme indicates the disease. An MRI and CT scan can also identify the loss of myelin in various regions of the brain. The nerve conduction study can also determine the efficiency of nerves conducting signal by measuring the time it takes for an electrical impulse to reach one part of the body to another, and when myelin is affected, the signal conduction can be slower. The diagnosis is also possible by detecting the activity of the enzyme in infants or from a fetus by amniocentesis.
Treatment
There is no treatment that can change the progression of the disease and accordingly, the treatment focuses on the management of the symptoms and by providing supportive care. Some of the treatment can include anticonvulsant medications for seizures, physical therapy to help with muscle tone, nutritional support and drugs to ease muscle spasticity. The stem cell transplant can improve outcomes among the infants if initiated before the symptoms develop.
References
https://ghr.nlm.nih.gov/condition/krabbe-disease#inheritance
http://my.clevelandclinic.org/health/articles/krabbe-disease
https://rarediseases.info.nih.gov/diseases/6844/krabbe-disease
https://rarediseases.org/rare-diseases/leukodystrophy-krabbes/
http://www.mayoclinic.org/diseases-conditions/krabbe-disease/basics/treatment/con-20029450
