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Case ReportMay-August, 2011/Vol 31/Issue 2

-143-J. Nepal Paediatr. Soc. May-August, 2011/Vol 31/Issue 2

Metachromatic Leucodystrophy: A Case Report

Karki S1, Rai GK2, Kafle R2

1Dr. Subhana Karki, MBBS, MD, Assistant Professor, 2Dr. Ganesh Kumar Rai, MBBS, DCH, MD, Associate Professor, 
3Dr. Raju Kafle, MBBS, MD. All from Kanti Children’s Hospital, Maharajgunj, Kathmandu, Nepal and affiliated to National 
Academy of Medical Sciences, Bir Hospital, Mahabauddha, Kathmandu, Nepal

Address for correspondence: Dr. Subhana Karki, E-mail: suvana.karki@gmail.com

Abstract
Metachromatic leukodystrophy (MLD) is an autosomal recessive neurodegenerative disorder 
characterized by deficient activity of the enzyme arylsulfatase-A. Deficiency of this enzyme results in 
intralysosomal storage of sphingolipid cerebroside 3-sulfates (sulfatides), which are abundant in myelin 
and neurons. A pathological hallmark of MLD is demyelination and neurodegeneration, causing various 
and ultimately lethal neurological symptoms. Its frequency is estimated to be 1/40,000 live births. The 
disease encompasses three clinical subtypes: late infantile (40% of the patients with MLD), juvenile 
(40%), and adult (20%).

The Case

A four years old male, presented with a three month history of a progressively unsteady gait and 
deterioration of speech for the same duration. He was 
apparently well three months back when he started 
having frequent fall with gradual impairment of walking. 
Since one and half months back, he was unable to walk 
even with support. In addition, also had progressive 
deterioration in his speech. Initially, speech was slurred 
and dysarthic and then he could speak only a few words 
with diffi culty. However, hearing and vision seemed to 
be normal. There was no history of unconsciousness, 
seizure, bowel and bladder incontinence or head injury. 
Detailed history revealed that he was born full term at 
home. Antenatal, perinatal and postnatal history was 
not signifi cant. His developmental milestones were 
within normal limits for age prior to the illness. The 
family history was however signifi cant; Among the 
four siblings, one sister had similar type of progressive 
deterioration of motor as well as intellectual function 
and had died at age of 5 years. Another sister who 
was eleven years old also had mental sub normality. 
However, there was no history of consanguinity. On 
examination, there was no obvious facial dysmorphism. 
His head circumference was 49.5 cm (10th percentile 
NCHS) and weight was below 5th percentile (HCHS) 
with normal height. He appeared dull and emotionally 
labile. All cranial nerves were clinically normal. On motor 
system examination, all extremities were hypotonic with 

power of 3/5 and absence of deep tendon refl exes. 
Planters were fl exure in response bilaterally. There were 
no sensory involvement; however cortical sensation 
and coordination could not be assessed. Rest of the 
general and systemic examinations was found to be 
normal. MRI revealed periventricular and deep white 
matter high signal areas (T2, NC, and axial view) and 
Leopard sign in contrast enhancement. CSF fi nding was 
normal. A diagnosis of MLD was suggested by the family 
history and clinical presentation. Further, neuroimaging 
abnormalities were well characterized and consisted 
of confl uent periventricular white matter abnormalities 
sparing the arcuate fi bers which have helped to confi rm 
the diagnosis of MLD. The patient was advised for 
physiotherapy and regular follow up.

Fig 1: Deep white matter high signal areas in T2 
weighted image.



-144-May-August, 2011/Vol 31/Issue 2 J. Nepal Paediatr. Soc.

leukodystrophy, which usually manifests in children 
between 12 and 18 months of age and is characterized 
by motor signs of peripheral neuropathy followed by 
deterioration in intellect, speech, and coordination. 
Within two years of on-set; gait disturbance, quadriplegia, 
blindness, and decerebrate posturing may be seen. 
Disease progression is inexorable, and death occurs 
six months to four years after onset of symptoms3. The 
extremities are hypotonic, and the deep tendon refl exes 
are absent or diminished4.

In juvenile MLD, the onset of symptoms is delayed 
to 5–10 yr of age. Deterioration in school performance 
and alterations in personality may herald the onset of 
the disease. This is followed by incoordination of gait, 
urinary incontinence, and dysarthria. In the terminal 
stages, generalized tonic-clonic convulsions are 
prominent and are diffi cult to control. Adult MLD occurs 
from the 2nd to 6th decade. Abnormalities in memory, 
psychiatric disturbances, and personality changes are 
prominent features4.

However, extrapyramidal signs are not a commonly 
described feature of MLD. Both juvenile and adult types 
of MLD may present with extra pyramidal and cerebellar 
signs5.

Neurophysiologic evaluation shows progressive 
changes in the VEPs, ABRs, and somatosensory-evoked 
potentials (SSEPs), and the nerve conduction velocities 
(NCVs) of the peripheral nerves are signifi cantly 
reduced4. Prenatal diagnosis by amniocentesis is 
possible in the fi rst trimester of pregnancy6. Since 
prenatal diagnosis is possible, the disease can be 
prevented, by fi rst trimester diagnosis of MLD by 
assaying ASA in chorionic villi or cultured fi broblasts and 
possible intervention thereafter7.

At T2-weighted MR imaging, metachromatic 
leukodystrophy manifests as symmetric confl uent areas 
of high signal intensity in the periventricular white matter 
with sparing of the subcortical U fi bers8.

The tigroid and “leopard skin” patterns of 
demyelination, which suggest sparing of the perivascular 
white matter, can be seen in the periventricular white 
matter and centrum semiovale8. In the later stage 
of metachromatic leukodystrophy, corticosubcortical 
atrophy often occurs, particularly when the subcortical 
white matter is involved8. Magnetic resonance (MR) 
imaging has be-come the primary imaging modality in 
patients with leukodystrophy and plays an important role 
in the identifi cation, localization, and characterization 
of underlying white matter abnormalities in affected 

Fig 3: T2-weighted MR image demonstrates bilateral 
confl uent areas of high signal intensity in the 
periventricular white matter. Note the classic sparing of 
the sub-cortical U fi bers (arrowheads).

Fig 2: “leopard skin” patterns of demyelination, which 
suggest sparing of the perivascular white matter.

Discussion

Metachromatic leukodystrophy is an autosomal 
recessive disorder caused by a defi ciency of the 
lysosomal enzyme arylsulfatase A. This enzyme is 
necessary for the normal metabolism of sulfatides, 
which are important constituents of the myelin sheath. 
The accumulation of sulfatides occurs not only in the 
central nervous system, but also in various other 
tissues, including the peripheral nervous system1. The 
excessive cerebroside sulfate is thought to cause myelin 
breakdown and destruction of oligodendroglia. 

Three different types of metachromatic 
leukodystrophy are recognized according to patient 
age at onset: late infantile, juvenile, and adult2. The 
most common type is late infantile metachromatic 



-145-J. Nepal Paediatr. Soc. May-August, 2011/Vol 31/Issue 2

patients. MR imaging has also been extensively used to 
monitor the natural progression of various white matter 
disorders and the response to therapy8.

Treatment

Bone marrow transplantation is a promising 
experimental therapy for the management of late infantile 
MLD4. Prenatal diagnosis of MLD is made by assay of 
arylsulfatase A in chorionic villi or cultured amniotic fl uid 
cells. Reports of hematopoietic cell transplantation (with 
or without mesenchymal stromal cells) for MLD have 
yielded a wide range of results9, 10. Umbilical cord blood 
transplantation may be a better option than bone marrow 
transplantation because stored and cataloged umbilical 
blood can be rapidly identifi ed and transplanted, 
producing a shorter period between diagnosis and 
transplantation, an important characteristic to consider 
in neurodegenerative diseases11.

References

1. Faerber EN, Melvin J, Smergel EM. MRI 
Appearances of metachromatic leukodystrophy. 
Pediatr Radiol 1999;29:669–72.

2. Kolodny EH. Sulfatide lipidosis: metachromatic 
leukodystrophy. In: Scriver CR, Beaedet Al, Sly 
W, Valle D, eds.The metabolic basis of inherited 
diseases. 6th ed. New York, NY: McGraw-Hill, 1989; 
1721–50.

3. Wolpert SM, Anderson ML, Kaye EM. Metabolic 
and degenerative disorders. In: Wolpert SM, Barnes 
PD, eds. MRI in pediatric neuroradiology. 3rd ed. St 
Louis, Mo: Mosby, 1992; 121–150. 

4. Michael V. Johnston. Neurodegenerative Disorders 
of Childhood. In: Behrman RE, Kliegman RM, 
Jenson HB, editors. Nelson Textbook of Pediatrics. 
18th ed. W.B. Saunders Company; 2008; 592-598.

5. Pandit L, Kapadia R, Kini P. Metachromatic 
Leukodystropy Presenting with extrapyramidal 
disturbances. Indian Pediatr 1994;31:690-94. 

6. Fensom AH, March J, Jackson M,McGuire VM, 
Vimal C, Nicolaides K,Sheridan R.First trimester 
diagnosis of metachromatic leucodystrophy. Clin 
Gen 1988; 34:122-25.

7. R.L. Koul A. GururajA.P. Chacko M.S. Elbualy 
S.R. P.Chand Late Infantile Metachromatic 
Leucodystrophy in Two Siblings. Indian Pediatr 
1994;31:694-98.

8. Jung-Eun Cheon, In-One Kim et al. Leukodystrophy 
in Children: A Pictorial Review of MR Imaging 
Features. J Continuing Med Edu Radiol 
2002;22:461-64. 

9. Kidd D, Nelson J, Jones F, et al. Long-term 
stabilization after bone marrow transplantation 
in juvenile metachromatic leukodystrophy. Arch 
Neurol 1998; 55:98–99.

10. Malm G, Ringden O, Winiarski J, et al. Clinical 
outcome in four children with metachromatic 
leukodystrophy treated by bone marrow 
transplantation. Bone Marrow Transplant 
1996;17:1003–8. 

11. Tyler Mark Piersonet al. Umbilical cord blood 
transplantation for juvenile metachromatic 
leukodystrophy. Ann Neurol 2008;64(5): 583–87.

How to cite this article ?
Karki S, Rai GK, Kafl e R. Metachromatic Leucodystrophy: A Case Report. J Nep Paedtr Soc 2011;31(2):143-145.


