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Krabbe disease AI simulator
(@Krabbe disease_simulator)
Hub AI
Krabbe disease AI simulator
(@Krabbe disease_simulator)
Krabbe disease
Krabbe disease (KD) (also known as globoid cell leukodystrophy or galactosylceramide lipidosis) is a rare and often fatal lysosomal storage disease that results in progressive damage to the nervous system. KD involves dysfunctional metabolism of sphingolipids and is inherited in an autosomal recessive pattern. The disease is named after Danish neurologist Knud Krabbe (1885–1961).
Symptoms in asymptomatic infantile-onset (less than 12 months after birth) and later-onset Krabbe disease present themselves differently. Of individuals with infantile-onset KD, 85–90% display progressive neurologic deterioration in infancy and death before the age of two. Symptoms include irritability, fevers, limb stiffness, seizures, feeding difficulties (like gastroesophageal reflux disease), vomiting, staring episodes, and slowing of mental and motor development. In the first stages of the disease, doctors often mistake the symptoms for those of cerebral palsy. Other symptoms include muscle weakness, spasticity, deafness, optic atrophy, optic nerve enlargement, blindness, paralysis, and difficulty when swallowing. Prolonged weight loss may also occur.[citation needed]
About 10–15% of individuals with later-onset KD 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.
Krabbe disease is caused by mutations in the GALC gene located on chromosome 14 (14q31), which is inherited in an autosomal recessive manner. Mutations in the GALC gene cause a deficiency of the enzyme galactosylceramidase (GALC). In rare cases, it may be caused by a lack of active saposin A (a derivative of prosaposin).
The buildup of unmetabolized lipids adversely affects the growth of the nerve's protective myelin sheath (the covering that insulates many nerves) resulting in demyelination and severe progressive degeneration of motor skills. As part of a group of disorders known as leukodystrophies, KD results from the imperfect growth and development of myelin.[citation needed]
Galactosylceramidase deficiency also results in a buildup of the glycosphingolipid psychosine, which is toxic to oligodendrocytes, a type of non-neuronal cells found in the nervous system, collectively termed neuroglia.
A few ways to help pinpoint the presence of Krabbe disease are known. Newborn screening for KD 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. Up to 5% GALC enzyme activity is observed in all symptomatic individuals with Krabbe disease. High concentration of psychosine in dried blood spots may also be identified as a marker for KD. A 2011 study discovered that individuals with KD, more so in later-onset individuals, tend to have an abnormal increase in CSF protein concentration.
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 myelin (e.g., luxol fast blue) may be used to aid diagnosis[citation needed].
Krabbe disease
Krabbe disease (KD) (also known as globoid cell leukodystrophy or galactosylceramide lipidosis) is a rare and often fatal lysosomal storage disease that results in progressive damage to the nervous system. KD involves dysfunctional metabolism of sphingolipids and is inherited in an autosomal recessive pattern. The disease is named after Danish neurologist Knud Krabbe (1885–1961).
Symptoms in asymptomatic infantile-onset (less than 12 months after birth) and later-onset Krabbe disease present themselves differently. Of individuals with infantile-onset KD, 85–90% display progressive neurologic deterioration in infancy and death before the age of two. Symptoms include irritability, fevers, limb stiffness, seizures, feeding difficulties (like gastroesophageal reflux disease), vomiting, staring episodes, and slowing of mental and motor development. In the first stages of the disease, doctors often mistake the symptoms for those of cerebral palsy. Other symptoms include muscle weakness, spasticity, deafness, optic atrophy, optic nerve enlargement, blindness, paralysis, and difficulty when swallowing. Prolonged weight loss may also occur.[citation needed]
About 10–15% of individuals with later-onset KD 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.
Krabbe disease is caused by mutations in the GALC gene located on chromosome 14 (14q31), which is inherited in an autosomal recessive manner. Mutations in the GALC gene cause a deficiency of the enzyme galactosylceramidase (GALC). In rare cases, it may be caused by a lack of active saposin A (a derivative of prosaposin).
The buildup of unmetabolized lipids adversely affects the growth of the nerve's protective myelin sheath (the covering that insulates many nerves) resulting in demyelination and severe progressive degeneration of motor skills. As part of a group of disorders known as leukodystrophies, KD results from the imperfect growth and development of myelin.[citation needed]
Galactosylceramidase deficiency also results in a buildup of the glycosphingolipid psychosine, which is toxic to oligodendrocytes, a type of non-neuronal cells found in the nervous system, collectively termed neuroglia.
A few ways to help pinpoint the presence of Krabbe disease are known. Newborn screening for KD 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. Up to 5% GALC enzyme activity is observed in all symptomatic individuals with Krabbe disease. High concentration of psychosine in dried blood spots may also be identified as a marker for KD. A 2011 study discovered that individuals with KD, more so in later-onset individuals, tend to have an abnormal increase in CSF protein concentration.
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 myelin (e.g., luxol fast blue) may be used to aid diagnosis[citation needed].
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