Metachromatische Leukodystrophie
Metachromatic leukodystrophy (MLD) is the most common hereditary (autosomal recessive) leukodystrophy and is one of the lysosomal storage disorders. It has characteristic imaging features including peri-atrial and to a lesser extent frontal horns leukodystrophy as well as periventricular perivenular sparing results in "tigroid pattern" on fluid-sensitive MRI sequences.
Epidemiology
It has an estimated prevalence of ~1:100,000 and typically manifests between 12 to 18 months of age. The disease can sometimes be classified according to the time of onset:
- late infantile: most common ~65% (range 50-80%)
- juvenile (onset between 3-10 years)
- adult (after age 16)
Clinical presentation
Clinical presentation depends on the age of onset.
- late infantile form
- gait abnormality, muscle rigidity, loss of vision, impaired swallowing, convulsions, dementia
- juvenile form
- impaired school performance; similar features as in late infantile form but slower progression
- adult form
- adult presentation accounts for 20% of all cases
- neuropsychiatric disorders
- gradual cognitive decline and dementia
- motor symptoms are a late feature
- often protracted course over 10 years
Because sulfatide accumulates also in the wall of the gallbladder, cholecystitis is a recognized complication .
Pathology
Metachromatic leukodystrophy is classified as a dysmyelinating disease and carries an autosomal recessive inheritance. It arises from a deficiency of the enzyme arylsulfatase A as a result of a mutation in the arylsulfatase A (ARSA) gene located on chromosome 22q13. This results in the accumulation of 3-O-sulfogalactosylceramide (sulfatide) in various organs including the central nervous system (Schwann cells, oligodendrocytes, and some neurons) impairing myelination and function .
Metachromatic refers to the histologic staining characteristic caused by abnormal accumulations of sulfatides in white matter .
Markers
- serum/urine arylsulfatase A levels: reduced
Radiographic features
MRI
Characterized by bilateral symmetrical confluent areas of periventricular deep white matter signal change, in particular around the atria and frontal horns with sparing of subcortical U fibers leading to a "butterfly pattern". Progression can lead to cortical and subcortical atrophy .
Signal characteristics
- T1: affected areas are low signal
- T1 C+ (Gd)
- no enhancement is characteristic
- however, some cases may show a linear punctate enhancement pattern within lesions
- multiple cranial nerve enhancement has been reported
- T2:
- affected areas are high signal and may show a "tigroid pattern" on axial plane or "leopard pattern" on sagittal plane representing sparing along the venules
- subcortical U-fibers are usually spared
- MR spectroscopy: (of affected white matter)
- reduced N-acetyl aspartate (NAA)
- increased myoinositol
- increased lactate
Differential diagnosis
In addition to many of the other leukodystrophies, a tigroid pattern of involvement may also be seen in:
Siehe auch:
und weiter:
Assoziationen und Differentialdiagnosen zu Metachromatische Leukodystrophie:
