Metachromatic Leukodystrophy

1. Ade Wijaya, MD – May 2020

2.  Lysosomal sphingolipid storage disorder
 Monogenic; autosomal recessive
 Deficiency of the enzyme arylsulfatase which
leads to a deficiency of sulfatide degradation
and its accumulates in oligodendrocytes,
Schwann cells and some neurons
 DEMYELINATION
 1 per 100000 live births
Gieselmann V, Krägeloh-Mann I. Metachromatic leukodystrophy–an update. Neuropediatrics. 2010 Feb;41(01):1-6.
Heim P , Claussen M , Hoff mann B et al . Leukodystrophy incidence in Germany . Am J Med Genet 1997 ; 71 : 475 – 478
Poorthuis BJ , Wevers RA , Kleijer WJ et al . The frequency of lysosomal storage diseases in The Netherlands . Hum Genet 1999 ; 105 : 151 – 156

3. Late Infancy (40-50 %)
Juvenile (30-40 %)
Adult (18-20 %)
Gieselmann V, Krägeloh-Mann I. Metachromatic leukodystrophy–an update. Neuropediatrics. 2010 Feb;41(01):1-6.

4.  Initial symptoms: psychotic and behavioural
abnormalities
 Slow decline in intellectual capabilities,
emotional instability, abnormal behaviour and
memory deficits
 Mean survival: 12 years
Hageman AT , Gabreels FJ , de Jong JG et al . Clinical symptoms of adult metachromatic leukodystrophy and arylsulfatase A pseudodefi ciency. Arch Neurol 1995
; 52 : 408 – 413
Kruse B , Hanefeld F , Christen HJ et al . Alterations of brain metabolites in metachromatic leukodystrophy as detected by localized proton magnetic resonance
spectroscopy in vivo . J Neurol 1993 ; 241 : 68 – 74

5. Tigroid pattern of the supratentorial white matter
Kim TS , Kim IO , Kim WS et al . MR of childhood metachromatic leukodystrophy. AJNR Am J Neuroradiol 1997 ; 18 : 733 – 738

6.  Increased sulfatide excretion in a 24-h urine
sample.
 Prenatal diagnosis
Gieselmann V, Krägeloh-Mann I. Metachromatic leukodystrophy–an update. Neuropediatrics. 2010 Feb;41(01):1-6.

7.  Hematopoetic stem cell transplantation
Gieselmann V, Krägeloh-Mann I. Metachromatic leukodystrophy–an update. Neuropediatrics. 2010 Feb;41(01):1-6.

8.  A rare lysosomal sphingolipid storage
disorder, caused by a deficiency of
arylsulfatase A (ASA)
 Autosomal recessive
 Demyelination
 Cognitive and behavioural problems
characterize the adult form
 Treatment: Hematopoetic stem cell
transplantation