|Year : 2013 | Volume
| Issue : 2 | Page : 113-115
Prima Cheryl D'souza1, Archanaa Vignesh1, K Subaschandra2, P John Mathai1
1 Department of Psychiatry, Father Muller Medical College, Kankanady, Mangalore, Karnataka, India
2 Department of Radiology, Father Muller Medical College, Kankanady, Mangalore, Karnataka, India
|Date of Web Publication||16-Sep-2013|
P John Mathai
Department of Psychiatry, Father Muller Medical College, Kankanady, Mangalore - 575 002, Karnataka
Source of Support: None, Conflict of Interest: None
Metachromatic leukodystrophy or Scholz's disease is a rare disorder transmitted as an autosomal recessive trait, leading to demyelination and neurological impairment. An 18-year-old boy was brought to the psychiatry out-patient department with a history of progressive decline of cognitive functions and self-help skills since 8 years. On examination, the patient was alert, easily distractible, and restless with stereotypic movements of the head. He was unable to speak, able to comprehend simple commands but not complex instructions and had an inappropriate affect. EEG revealed frequent intermittent clusters of biphasic spike-slow wave and sharpish discharges arising from bilateral fronto - centro - temporal regions. MRI brain showed non-enhancing altered signal intensity involving bilateral periventricular deep white matter, with a possibility of metachromatic leukodystrophy. Metachromatic leukodystrophy is a progressive demyelinating disorder which may present with cognitive or behavioral symptoms. It may be misdiagnosed as a psychiatric disorder, delaying intervention, leading to unnecessary exposure to neuroleptics and increasing financial burden for the family.
Keywords: Cognitive decline, demyelinating disorder, metachromatic leukodystrophy
|How to cite this article:|
D'souza PC, Vignesh A, Subaschandra K, Mathai P J. Metachromatic leukodystrophy. Muller J Med Sci Res 2013;4:113-5
| Introduction|| |
Metachromatic leukodystrophy (MLD) or Scholz's disease is a rare disorder leading to demyelination and neurological impairment.  The pathological accumulation of sulfatides in the nervous system (myelin, neurons and glial cells) results in neurological symptoms, intellectual decline, and motor signs.  It is localized in chromosome 22. The disease is transmitted as an autosomal recessive trait, but some sporadic cases have been reported.  Here, we report a case with juvenile onset of MLD.
| Case Report|| |
Mr. X, an 18-year-old boy, was brought to the psychiatry out-patient department by his family with a history of progressive decline of cognitive functions and self-help skills since 8 years. The initial symptoms were difficulty in attention and concentration, disturbances in memory, inability to learn and decline in scholastic performance. The symptoms progressed over the next few years, with increase in activity, restlessness, soiling of clothes with stools and urine, loss of speech and language, impaired social interaction, and stereotypic head movements. He also needed help with his daily activities like dressing and bathing. At presentation to the OPD he was unable to speak and communicate his needs, was indifferent to the external environment and had stereotypical movements of the head. He was able to have minimal reciprocal communication exclusively with his mother.
The patient was born of a second degree consanguineous marriage. There was a family history of congenital heart disease in mother's paternal cousin who died at the age of 20 years, but no history of psychiatric or neurological illness in the family. The patient's mother had tried terminating the pregnancy at 1½ months of gestation but had failed. At 5 months of gestation, mother had developed allergic reaction to an intramuscular injection. He was born of a full term normal hospital delivery with an uneventful perinatal period, and had attained all developmental milestones at appropriate age. He had no significant medical or neurological disorders in early childhood. He was good in studies and would stand first in class till 4 th std, until the onset of symptoms at 10 years of age. For the present complaints patient was treated by a psychiatrist in Shimoga with Tab. Olanzapine 2.5 mg ½ at night and Cap. Piracetam for 2 to 3 months which was stopped due to lack of improvement.
On examination the patient was alert, easily distractible, and restless with stereotypic movements of the head. It was difficult to establish meaningful communication with him. He could not speak, was able to comprehend simple commands but not complex instructions. He had an inappropriate affect. Detailed examination of his cognitive functions, thinking and perception couldn't be done. His deep tendon reflexes were exaggerated and plantar reflex was extensor bilaterally. There were no other localizing or lateralizing signs. Other systems were within normal limits.
A provisional diagnosis of progressive neuropsychiatric disorder (Unspecified Organic Mental Disorder) was made with a differential of leukodystrophy or metabolic storage disease. He was admitted in psychiatry ward for medical and neurological investigations. Routine hemogram, renal function test, liver function test, and thyroid function test were within normal limits.
The drug induced sleep EEG revealed a background activity consisting of symmetrical synchronous low voltage fast beta, with evidence of frequent intermittent clusters of biphasic spike-slow wave and sharpish discharges arising from bilateral (L > R) fronto - centro - temporal regions with inflection point over F3, F7, F4, F8.
MRI brain showed non-enhancing altered signal intensity involving bilateral periventricular deep white matter. Axial T2 [Figure 1] and flair images [Figure 2] showed bilateral symmetric confluent areas of high signal intensity in periventricular white matter with sparing of subcortical ''U'' fibers, resembling tigroid/leopard skin pattern, suggesting a possibility of metachromatic leukodystrophy.
A referral to neurologist was given, who made a provisional diagnosis of leukodystrophy with a differential of metachromatic leukodystrophy, and advised evaluating urine sulfatide level and nerve biopsy. The patient's family was unwilling for these investigations and requested for discharge. Hence, the patient was referred to NIMHANS for further evaluation and management.
| Discussion|| |
Metachromatic leukodystrophy is a lysosomal storage disease caused by deficiency of enzyme arylsulfatase A (ARSA), which prevents the conversion of sulfatide to cerebroside and results in the accumulation of the former. It usually manifests between 1 and 4 years. A late-infantile (onset before 3 years of age), a juvenile form (onset before 16 years) and an adult form are usually distinguished. Rapid motor decline is typical for the late-infantile and the juvenile forms, but the juvenile form may be preceded by cognitive and behavioral problems, which mainly characterizes the adult form also. 
The clinical features include slowly evolving intellectual decline or behavioral abnormality, followed by spastic weakness, hyper-reflexia, Babinski signs, stiff, short stepped gait, with or without a poly neuropathy. As the disease progresses over a period of 3-5 years, there may be loss of vision, speech, and then of hearing and finally a state of virtual decerebration. In the absence of neurological signs, misdiagnosis of psychiatric disease is common.  Progression to a bed ridden quadriplegic state without speech or comprehension occurs over 1-3 year period, but occurs more slowly in late onset types. 
Demyelination is the hallmark of MLD. There is widespread degeneration of myelinated fibers in the cerebrum, cerebellum, spinal chord, and peripheral nerves. The presence of highly toxic metachromatic granules in glial cells and engorged macrophages is characteristic. The stored material, sulfatide, stains brown - orange with aniline dyes and is also PAS - positive in frozen sections. The diagnosis can be made from a biopsy of a peripheral nerve showing characteristic histologic changes, and MRI. The CSF protein is elevated (75-250 mg/dL). There is a marked increase in sulfatide in urine and an absence of arylsulfatase A in WBC's, serum, and cultured fibroblasts.  The study of the gene that codes for ARSA is the most reliable method of diagnosis, to avoid misdiagnosis due to the presence of pseudodeficit. 
The conventional therapeutic approaches are essentially symptomatic in order to restore the enzyme activity of arylsulfatase A and prevent the progression of the pathological accumulation of sulfatides and consequently reduce morbidity associated with MLD.  Treatment is being tried with enzyme replacement and bone marrow transplantation. Marrow transplant may be useful early in the disease and in the treatment of an asymptomatic sibling of an index case, but is of less benefit once patient becomes symptomatic. Interest in the disease has increased as therapeutic options such as stem cell transplantation, enzyme replacement and gene therapy are being explored.  Autologous hematopoietic stem/progenitor cells can be genetically modified to constitutively express supra-physiological levels of arylsulfatase-A and may become a more effective source of functional enzyme when transplanted in patients with MLD. 
| Conclusion|| |
Metachromatic leukodystrophy is a demyelinating disorder with a progressive course, and symptomatic treatment. Though in this case the diagnosis could not be confirmed, it is being reported not only for its rare incidence but also because it represents a primary neurological/medical disorder presenting with cognitive or behavioral symptoms. Due to this it may be misdiagnosed as a psychiatric disorder, thus delaying evaluation and intervention, leading to unnecessary exposure to neuroleptics, also increasing financial burden for the family. Early detection and explaining the prognosis to the family may reduce their social and financial burden.
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[Figure 1], [Figure 2]