Inheritance:
Autosomal recessive
Frequency:
Heterozygote prevalence estimated at
~1%
Homozygote incidence estimated at ~1
in 40,000 in the United States
Locus:
ARSA gene at 22q13.31-qter (arylsulfatase
A)
Defining characteristics:
Progressive deterioration of motor
and neurocognitive function
Demyelination of axons and peripheral
nerves
Mental deterioration
Late Juvenile and Adult (6+ years of
age)
Decreased work or school performance,
behavioral changes, memory loss, possible seizures, psychoses,
gradual loss of motor skills, optic atrophy
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Natural History:
There are at least three types of MLD
that vary by age of onset and severity, but there is
some disagreement in the literature. The following is
from OMIM:
Infantile form onset by age 2, with
death usually by 5 years
Juvenile form onset age 4 to 10 years
Late-onset form onset at any age beyond
3 years
Demarcation of juvenile forms from
adult forms age 16 to 21
In the late-onset forms,
the patient is commonly receiving psychiatric treatment
before dementia begins; accelerated mental deterioration
and disorders of movement lead to diagnosis of MLDBack
to the topPsychiatric
characteristics in late-onset cases:Attention difficultiesPoor
judgmentSocially inappropriate behaviorBehavioral disorganizationDementiaImpulsiveness
Hyde, Zeigler, and Weinberger
(1992) Adolescent and early adult-onset MLD
Auditory hallucinations
in every case reporting hallucinations
Schizophrenia-like
behaviors: thought fragmentation, catatonic posturing,
bizarre
gesturing, poor concentration,
inappropriate giggling, talking to oneself, poor insight Patients
with hallucinations, primarily auditory 10/55
(18%)Patients with delusions 15/55
(27%)Patients diagnosed with schizophrenia or psychosis 19/55
(35%)Patients with hallucinations, delusions, and/or
diagnosed with
schizophrenia or psychosis 29/55
(53%)
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ReferencesHyde,
T. M., Ziegler, J. C., Weinberger, D. R. Psychiatric
disturbances in metachromatic leukodystrophy. Arch
Neurol 49: 401-406 (1992).Shapiro, E. G., Lockman,
L. A., Knopman, D., Krivit, W. Characteristics of the
dementia in late-onset metachromatic leukodystrophy.
Neurology 44: 662-665 (1994).Tylki-Szymanska, A., Berger,
J., Loschl, B., Lugowska, A., Molzer, B. Late juvenile
metachromatic leukodystrophy (MLD) in three patients
with similar clinical course and identical mutation
on one allele. Clin Genet 50: 287-292 (1996).eMedicinehttp://www.emedicine.com/ped/topic2893.htm#target11
OMIM
http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?250100
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Velocardiofacial
Disorder