Abstract
The possible relationship between the metachromatic leukodystrophies and neuropsychiatric disorders is reviewed. Four kinds of evidence are considered: psychiatric symptoms as preemergent markers of the neurodegenerative process; increased behavioral problems in leukodystrophy familes; screening for low enzyme levels among psychiatric populations; and studies in model systems. Whereas the basic postulate of an increased risk for psychiatric problems among individuals with lower levels of the enzymes deficient in the leukodystrophies remains attractive, there is no strong evidence in its support. Low enzyme levels can be found in psychiatric populations, but they may not be any more frequent than in the general population.
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Alves D., Pires M. M., Guimaraes A., and Miranda M. C. (1986) Four cases of late onset metachromatic leucodystrophy in a family: clinical, biochemical and neuropathological studies.J. Neurol. Neurosurg. Psychiat. 49, 1417–1422.
Austin J., Armstrong D., Fouch S., Mitchell C., Stumpf D., Shearer L., and Briner O. (1968) Metachromatic leukodystrophy (MLD) VIII. MLD in adults; Diagnosis and pathogenesis.Arch. Neurol. 18, 225–240.
Besson J. A. O. (1980) A diagnostic pointer to adult metachromatic leukodystrophy.Br. J. Psychiat. 137, 186–187.
Betts T. A., Smith T., and Kelly R. E. (1968) Adult metachromatic leukodystrophy (sulfatide lipidosis) simulating acute schizophrenia.Neurology 18, 1140–1142.
Christomanou H., Jaffe S., Martinius J., Cap C., and Betke K. (1981) Biochemical, genetic, psychometric and neuropsychological studies in heterozygotes of a family with globoid cell leukodystrophy (Krabbe).Hum. Genet. 58, 179–183.
Christomanou H., Martinius J., Jaffe S., Betke K., and Forster C. (1980) Biochemical, psychometric and neurophysiological studies in heterozygotes for various lipidoses.Hum. Genet. 55, 103–110.
Clarke J. T. R., Skomorowski M. A., and Chang P. L. (1989) Marked clinical differences between two sibs affected with juvenile metachromatic leukodystrophy.Am. J. Med. Genet. 33, 10–13.
Finelli P. F. (1985) Metachromatic leukodystrophy manifesting as a schizophrenic disorder: computed tomographic correlation.Ann. Neurol. 40, 354–355.
Fischer N. R., Cope S. J., and Lishman W. A. (1987) Metachromatic leukodystrophy: conduct disorder progressing to dementia.J. Neurol. Neurosurg. Psychiat. 50, 488, 489.
Fluharty A. L., Neidergard L., Holtzman D., and Kihara H. (1986) Late-onset Krabbe disease initially diagnosed as cerebroside sulfatase activator deficiency.Metab. Brain Dis. 1, 187–195.
Fluharty A. L., Stevens R. L., and Kihara H. (1978) Cerebroside sulfate hydrolysis by fibroblasts from a metachromatic leukodystrophy parent with deficient arylsulfatase A.J. Pediatr. 92, 782–784.
Gordon N. (1978). The insidious presentation of the juvenile form of metachromatic leukodystrophy.Postgrad. Med. J. 54, 335–337.
Haltia T., Palo J., Haltia M., and Ican A. (1980) Juvenile metachromatic leukodystrophy: clinical, biochemical and neuropathologic studies in nine new cases.Arch. Neurol. 37, 42–46.
Herska M., Moscovich D. G., Kalian M., Gottlieb D., and Bach G. (1987) Aryl sulfatase A deficiency in psychiatric and neurologic patients.Am. J. Med. Genet. 26, 629–635.
Herz B. and Bach G. (1984) Arylsulfatase A in pseudodeficiency.Hum. Genet. 66, 147–150.
Hoes M. J., Lamers K. J., Hommes O. R. and ter Haar B. (1978) Arylsulfatase A values in four generations of one family and some reflections about the genetics.Clin. Neurol. Neursurg. 80, 174–188.
Hoes M. J., Lamers K. J., and Weaver R. A. (1988) Use of arylsulfatase A in chronic psychiatric patients.Am. J. Psychiat. 145, 3.
Hohenschutz C., Eich P., Friedl W., Waheed A., Conzelmann E., and Propping P. (1989) Pseudodeficiency of arylsulfatase A: A common genetic polymorphism with possible disease implications.Hum. Genet. 89, 45–48.
Hohenschutz C. Friedl W., Schlör K.-H., Waheed A., Conzelmann E., Sandhoff K., and Propping P. (1988) Probable metachromatic leukodystrophy/pseudodeficiency compound heterozygote at the arylsulfatase A locus with neurological and psychiatric symptomatology.Am. J. Med. Genet. 31, 169–175.
Hulyalkar A. R., Rena N., and Manowitz P. (1984) Arylsulfatase A variants in patients with alcoholism.Alcoholism: Clinical and Experimental Research 8, 337–341.
Kihara H., Tsay K., and Fluharty A. L. (1983). Effect of HEPES on the fibroblast cerebroside sulfate loading tests.Biochem. Med. 29, 278–284.
Kohn H., Manowitz P., Miller M., and Kling A. (1988). Neuropsychological deficits in obligatory heterozygotes for metachromatic leukodysrophy.Hum. Genet. 79, 8–12.
Kolodny E. H. (1989) Metachromatic leukodystrophy and multiple sulfatase deficiency: sulfatide lipidosis.The Metabolic Basis of Inherited Disease, 6th Ed. (Scriver C. R., Beaudet A. L., Sly W. S., and Valle D. eds.), pp. 1721–1750, McGraw-Hill, New York.
Kolodny E. H., Raghavan S. S., Lott I. T., and Sergay S. M. (1981) Low sulfatidase activity and demyelinating disease.Neurology 31, 86.
Kothbauer P., Jellinger K., Gross H., Molzer B., and Bernheimer H. (1977) Adulte metachromatische Leukodystrophie unter dem Bild einer schizophrenen Psychose.Arch. Psychiatr. Nervenkr. 224, 379–387.
Lejoyeux M., Dubois G., Turpin J.-C., Baumann N., and Lemperiere T. (1989) Arylsulfatase A activity among psychotic patients.Psychiat. Res. 30, 107–108.
Louis A. I. and Fluharty A. L. (1990) Activator-dependent hydrolysis of myelin cerebroside sulfate by arylsulfatase A.Dev. Neurosci. (in press).
MacFaul R., Cavanagh N., Lake B. D., Stephens R., and Whitfield A. E. (1982) Metachromatic leukodystrophy: review of 38 cases.Arch. Dis. Child. 57, 168–175.
Mahon-Haft H., Stone R. K., Johnson R., and Shah, S. (1981) Biochemical abnormalities of metachromatic leukodystrophy in an adult psychiatric population.Am. J. Psychiat. 138, 1372–1374.
Manowitz, P., Goldstein L., and Nora R. (1981). An arylsulfatase A variant in schizophrenic patients: Preliminary report.Biol. Psychiat. 16, 1107–1113.
Manowitz P., Kling A., and Kohn H. (1978) Clinical course of adult metachromatic leukodystrophy presenting as schizophrenia.J. Nerv. Ment. Dis. 166, 500–506.
Müller D., Pilz H., and ter Meulen V. (1969) Studies on adult metachromatic leukodystrophy. Part I. Clinical, morphological, and histochemical observations in two cases.J. Neurol. Sci. 9, 567–584.
Olmstead C. E. (1985) Slowed locomotor recovery following sciatic nerve crush in mice heterozygous for galactosylceramidase deficiency (C57bl/6j-twi “Twitcher”)Soc. Neurosci. Abst. 11, 399.
Olmstead C. E. (1987) Neurological and neurobehavioral development in the twitcher mouse.Behav. Brain Res. 25, 143–153.
Olmstead C. E. (1989) Spatial learning deficits in two year old mice heterozygous for thetwitcher (C57Bl/6j/twi) mutation.Soc. Neurosci. Abst. 15, 685.
Omenn G. S. (1976) Inborn errors of metabolism: Clues to understanding human behavioral disorders.Behav. Genet. 6, 263–284.
Pilz H., Duensing I., Heipertz R., Seidel D., Lowitzsch K., Hopf H. C., and Goebel H. H. (1977) Adult metachromatic leukodystrophy. I. Clinical manifestation in a female aged 44 years, previously diagnosed in the preclinical state.Eur. Neurol. 15, 301–307.
Porter M. T., Fluharty A. L., Trammell J., and Kihara H. (1971) A correlation of intracellular cerebroside sulfatase activity in fibroblasts with latency in metachromatic leukodystrophy.Biochem. Biophys. Res. Comm. 44, 660–666.
Propping P. (1983) Genetic disorders presenting as “schizophrenia,” Karl Bonhoeffer’s early iew of the psychoses in light of human genetics.Hum. Genet. 65, 1–10.
Propping P. (1989)Psychiatrische genetik. Befunde and konzept. Springer-Verlag, Berlin.
Propping P., Friedl W., Huschka M., Schlör K.-H., Reimer F., Lee-Vaupel M., Conzelmann E., and Danhoff K. (1986) The influence of low arylsulfatase A activity on neuropsychiatric morbidity: A large-scale screening in patients.Hum. Genet. 74, 244–248.
Reider-Grosswasser I. and Bornstein N. (1987) CT and MRI in late-onset metachromatic leukodystrophy.Acta Neurol. Scand. 75, 64–69.
Shah S. N., Johnson R. C., Stone R. K., and Mahon-Haft H. (1985) Prevalence of partial cerebroside sulfate sulfatase (arylsulfatase A) defect in adult psychiatric patients.Biol. Psychiat. 20, 50–57.
Skomer C., Stears J., and Austin J. (1983) Metachromatic leukodystrophy (MLD) XV. Adult MLD with focal lesions by computed tomography.Arch. Neurol. 40, 354–355.
Suzuki K. and Suzuki Y. (1989) Galactosylceramide lipidosis: Globoid cell leukodystrophy (Krabbe’s disease),The Metabolic Basis of Inherited Disease, 6th Ed. (Scriver C. R., Beaudet A. L., Sly W. S., and Valle D., eds.), pp. 1699–1720, McGraw-Hill, New York.
Taketomi T., Kasama T., Hara A., and Mizushima S. (1981) Abnormality of sphingolipids in correlation with histological damages in the central and peripheral nervous systems of a patient with adult form of metachromatic leukodystrophy.Jpn. J. Exp. Med. 51, 237–246.
Vogel F. (1984) Clinical consequences of heterozygosity for autosomal-recessive diseases.Clin. Genet. 25, 381–415.
Vogel F. (1987) Research strategies in human behaviour genetics.J. Med. Genet. 24, 129–138.
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Fluharty, A.L. The relationship of the metachromatic leukodystrophies to neuropsychiatric disorders. Molecular and Chemical Neuropathology 13, 81–94 (1990). https://doi.org/10.1007/BF03159910
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DOI: https://doi.org/10.1007/BF03159910