Metachromatic Leukodystrophy Clinical Presentation
- Author: Alan K Ikeda, MD; Chief Editor: Bruce Buehler, MD more...
History
Features of symptoms found in patients with each of the 4 forms of metachromatic leukodystrophy (MLD) are shown below.
The infantile form includes the following:
- Gait disturbances
- Memory deficits
- Seizures (may be present)
- Loss of motor developmental milestones
- Decreased attention span
- Speech disturbances
- Decline in school performance
The early juvenile form includes the following:
- Gait disturbances
- Tremors
- Clumsiness
- Loss of previously achieved skills
- Intellectual decline
- Behavioral changes
- Seizures (possible)
The late juvenile and adult forms include the following:
- Decreased work or school performance
- Behavioral changes
- Memory loss
- Seizures (may be present)
- Psychoses
- Gradual loss of motor skills
Physical
Neurodevelopmental tests demonstrate the following findings in patients with infantile or early juvenile metachromatic leukodystrophy:
- Loss of previously achieved developmental milestones
- Tremors
- Truncal ataxia
- Hyperreflexia progressing to hyporeflexia
- Hypotonia
- Gait abnormalities
- Optic atrophy
Neurocognitive tests demonstrate the following abnormalities in patients with late juvenile or adult metachromatic leukodystrophy:
- Dementia
- Memory loss
- Disinhibition
- Impulsiveness
- Decreased motor function
- Optic atrophy
Gieselmann V, Krägeloh-Mann I. Metachromatic leukodystrophy--an update. Neuropediatrics. Feb 2010;41(1):1-6. [Medline].
Anlar B, Waye JS, Eng B. Atypical clinical course in juvenile metachromatic leukodystrophy involving novel arylsulfatase A gene mutations. Dev Med Child Neurol. May 2006;48(5):383-7. [Medline].
von Figura K, Gieselman V, Jaeken J. Metachromatic leukodystrophy. In: Scriver C, Beadet A, Valle D, Sly W, et al, eds. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. McGraw-Hill Professional; 2001.
Estrov Y, Scaglia F, Bodamer OA. Psychiatric symptoms of inherited metabolic disease. J Inherit Metab Dis. Feb 2000;23(1):2-6. [Medline].
Fukutani Y, Noriki Y, Sasaki K, et al. Adult-type metachromatic leukodystrophy with a compound heterozygote mutation showing character change and dementia. Psychiatry Clin Neurosci. Jun 1999;53(3):425-8. [Medline].
Meikle PJ, Grasby DJ, Dean CJ. Newborn screening for lysosomal storage disorders. Mol Genet Metab. Aug 2006;88(4):307-14. [Medline].
Faerber EN, Melvin J, Smergel EM. MRI appearances of metachromatic leukodystrophy. Pediatr Radiol. Sep 1999;29(9):669-72. [Medline].
Krivit W. Allogeneic stem cell transplantation for the treatment of lysosomal and peroxisomal metabolic diseases. Springer Semin Immun. 2004;26:119-132. [Medline].
Martin PL, Carter SL, Kernan NA. Results of the cord blood transplantation study (COBLT): outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with lysosomal and peroxisomal storage diseases. Biol Blood Marrow Transplant. Feb 2006;12(2):184-94. [Medline].
Consiglio A, Quattrini A, Martino S, et al. In vivo gene therapy of metachromatic leukodystrophy by lentiviral vectors: correction of neuropathology and protection against learning impairments in affected mice. Nat Med. Mar 2001;7(3):310-6. [Medline].
Matzner U, Habetha M, Gieselmann V. Retrovirally expressed human arylsulfatase A corrects the metabolic defect of arylsulfatase A-deficient mouse cells. Gene Ther. May 2000;7(9):805-12. [Medline].
Kawabata K, Migita M, Mochizuki H. Ex vivo cell-mediated gene therapy for metachromatic leukodystrophy using neurospheres. Brain Res. Jun 13 2006;1094(1):13-23. [Medline].
Matzner U, Herbst E, Hedayati K, et al. Enzyme replacement improves nervous system pathology and function in a mouse model for metachromatic leukodystrophy. Hum Mol Genet. May 2005;14(9):1139-1152. [Medline].
Givogri MI, Galbiati F, Fasano S. Oligodendroglial progenitor cell therapy limits central neurological deficits in mice with metachromatic leukodystrophy. J Neurosci. Mar 22 2006;26(12):3109-19. [Medline].
Alessandri MG, De Vito G, Fornai F. Increased prevalence of pervasive developmental disorders in children with slight arylsulfatase A deficiency. Brain Dev. Oct 2002;24(7):688-92. [Medline].
Hernandez-Palazon J. Anaesthetic management in children with metachromatic leukodystrophy. Paediatr Anaesth. Oct 2003;13(8):733-4. [Medline].
Sevin C, Aubourg P, Cartier N. Enzyme, cell and gene-based therapies for metachromatic leukodystrophy. J Inherit Metab Dis. Apr 2007;30(2):175-83. [Medline].
| Form | Age at Onset (y) | Inheritance Pattern | Frequency | Neurocognitive Deficit | Progression | Effect of Bone Marrow Transplantation |
| Late infantile | < 4 | Autosomal recessive | Most common | Motor milestones lost, neurocognitive functions lost | Death within 5-6 y | Not helpful in symptomatic patients; may halt cognitive deterioration in asymptomatic patients |
| Early juvenile | 4-6 | Autosomal recessive | Less common | Motor milestones lost, learning and behavior impaired | Death within 10-15 y | May be beneficial in symptomatic and asymptomatic patients |
| Late juvenile | 6-16 | Autosomal recessive | Rare | Personality changes, behavioral changes, dementia, psychoses, decreased school or work performance | Slow | May be beneficial in asymptomatic or mildly symptomatic patients |
| Adult | >16 | Autosomal recessive | Rare | Personality changes, behavioral changes, dementia, psychoses, decreased school or work performance | Slow | May be beneficial in asymptomatic or mildly symptomatic patients |
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