Krabbe disease

Krabbe disease (KD) (also known as globoid cell leukodystrophy

10–15% of individuals with later-onset Krabbe disease have a much slower disease progression. These individuals may also display symptoms such as esotropia, slurred speech, and slow development or loss of motor milestones.^[5]

Causes

Krabbe disease is caused by

There are a few ways to help pinpoint the presence of Krabbe disease. Newborn screening for Krabbe disease includes assaying dried blood cells for GALC enzyme activity and molecular analysis for evidence of GALC enzyme mutations. Infants displaying low enzyme activity and/or enzyme mutations should be referred for additional diagnostic testing and neurological examination.^[10] 0-5% GALC enzyme activity is observed in all symptomatic individuals with Krabbe disease.^[5] High concentration of psychosine in dried blood spots may also be identified as a marker for Krabbe disease.^[11] A 2011 study discovered that individuals with Krabbe disease, more so in later-onset individuals, tend to have an abnormal increase in CSF protein concentration.^[12]

The disease may be diagnosed by its characteristic grouping of certain cells (multinucleated globoid cells), nerve demyelination and degeneration, and destruction of brain cells. Special stains for

New York,[13] Missouri and Kentucky^[14] include Krabbe in the newborn screening panel.^[15] Indiana started screening in 2020.^[16]

Treatment

Although there is no known

A 15-year study on the developmental outcomes of children with Krabbe disease who underwent HSCT in the first seven weeks after birth found that patients have a better prognosis for both lifespan and functionality, with a slower progression of the disease.[17] Even symptomatic individuals with later-onset Krabbe disease may benefit from HSCT if diagnosed early enough.^[18] Umbilical-cord blood is typically used as the source for the transplant stem cells.^[19] Clinical trials for gene therapy are currently enrolling patients.^[20]

Management

Symptom management can be particularly difficult for individuals with infantile onset, as symptoms tend to progress rapidly.^[19] Because there is no treatment for Krabbe disease, management of the condition is typically supportive and aimed at alleviating symptoms. Frequent evaluation is encouraged in order to anticipate the onset of, and preparation for, certain symptoms.^[5] Physical therapy can help to alleviate motor difficulties and increase strength, mobility, and flexibility.^[5]

Gastrostomy tubes are used to circumvent feeding difficulties and prevent aspiration. A simultaneous gastrostomy tube insertion and Nissen fundoplication procedure is commonly performed to prevent the need for a secondary surgical procedure.^[19] Individuals with Krabbe disease with severe motor deficits tend to be more susceptible to overfeeding, as they require less calorie consumption and thus consume fewer calories than what caretakers may expect.^[19] There is also evidence that routine vaccines may accelerate disease progression; many individuals with Krabbe disease tend to not follow traditional vaccination procedures.^[19]

Prognosis

In infantile Krabbe disease, death usually occurs in early childhood. A 2011 study found one-, two-, and three-year survival rates of 60%, 26%, and 14%, respectively, with a few surviving longer. Patients with late-onset Krabbe disease tend to have a slower progression of the disease and live significantly longer.^[2]

Epidemiology

This disease does not only impact humans, but other animals such as monkeys, mice, and dogs have been observed to develop Krabbe disease as well. While certain gene deletions are more frequent than others, novel mutations resulting in Krabbe disease have been discovered worldwide. Most commonly, the underlying cause of the disease is a deletion of a GALC gene, which causes a deficiency in the GALC enzyme. This is the circumstance in 80% of patients who have European and Mexican origins.^[21] The mortality rate of early infantile Krabbe disease is 90% before the age of two. Later onset of symptoms is associated with longer life expectancy, with older children generally surviving two to seven years after the initial diagnosis.^[22]

Krabbe disease occurs in about one in 100,000 births.

Time of onset also varies in frequency by location. Early infantile Krabbe Disease is the most common form of the disease overall, but Nordic communities tend to have even higher rates of early infantile onset Krabbe disease, while Southern European countries have higher incidences of late-onset cases. It is difficult to estimate the incidence of adult-onset Krabbe disease, due to discrepancies in classifying cases late-onset versus adult-onset.[24]

Society and culture

Former Buffalo Bills quarterback Jim Kelly has been a leader in gaining recognition and research funding for Krabbe disease following the diagnosis of his son, Hunter, in 1997. Hunter Kelly died of the disease on August 5, 2005, at the age of eight.^{[citation needed]} They created Hunter's Hope - a foundation that seeks to advance Newborn Screening, research and treatments, and provides support to families of leukodystrophy children.^{[citation needed]}

Family advocacy is a critical part of advancing newborn screening, and many Krabbe families have made significant advocacy progress in their states.^{[citation needed]}

As an example, Cove Ellis is a child from

Krabbe disease is found in mice[28] may also be found in cats^[29] and in dogs, particularly the West Highland White Terriers and Cairn Terriers.^[30][31]

See also

• Maria Luisa Escolar
• The Myelin Project
• The Stennis Foundation
• KrabbeConnect
• The Legacy of Angels Foundation
• Hunter's Hope Foundation

References