Elsevier

Pediatric Neurology

Volume 38, Issue 5, May 2008, Pages 363-366
Pediatric Neurology

Case report
Dilated Perivascular Spaces: An Informative Radiologic Finding in Sanfilippo Syndrome Type A

https://doi.org/10.1016/j.pediatrneurol.2008.01.009Get rights and content

Mucopolysaccharidosis type IIIA, or Sanfilippo syndrome type A, is a lysosomal storage disorder caused by deficiency of heparan N-sulfamidase, resulting in defective degradation and subsequent storage of heparan sulfate. It is characterized by progressive nervous system involvement. Cribriform changes in the corpus callosum, basal ganglia, and white matter, diffuse high-intensity signal in the white matter, and cerebral atrophy have been described in patients with this disorder. This case report describes a child with Sanfilippo syndrome type A who exhibited fairly mild clinical findings but an unusual magnetic resonance imaging pattern that included multiple moderate-sized cysts (probably enlarged perivascular spaces) within the corpus callosum and an abnormal appearance of the clivus and cervical vertebrae. This case calls attention to the variety of appearances possible with magnetic resonance imaging in Sanfilippo syndrome type A.

Introduction

Mucopolysaccharidosis type III, or Sanfilippo syndrome, is an autosomal recessive inherited disease caused by lack of degradation of heparan sulfate in lysosomes. In the most common subtype (type IIIA), deficiency of sulfamidase (N-sulfoglucosamine sulfohydrolase, EC 3.10.1.1; also known as heparan N-sulfatase) results in lysosomal storage of heparan sulfate and leads to severe neurodegeneration. Affected patients develop progressive dementia (often including rapid loss of social skills, mental decline, delayed speech, and disturbed sleep patterns), hirsutism, coarse facies, diarrhea, hyperactivity, aggressive behavior, and gait disturbances; ultimately, the result is early death. The skeletal pathology is relatively mild, and often develops after the diagnosis is established. Joint stiffness and hepatosplenomegaly are found mostly in older patients [1], [2], [3], [4], [5].

The incidence of mucopolysaccharidosis type III subtypes ranges from 1:20,000 to 1:324,000 in different geographic regions but mucopolysaccharidosis type IIIA is the most common type in northern Europe and Australia. Clinical onset in severely affected mucopolysaccharidosis type IIIA patients usually comes after 2 to 3 years of apparently normal development. In less severe cases, the diagnosis may be missed because of the mild somatic and radiologic features, and because of false-negative findings in urine screening for elevated heparan sulfate [3], [4], [5], [6], [7].

The first imaging studies of central nervous system involvement of mucopolysaccharidoses were done with x-ray computed tomography. Because the findings were nonspecific (low-density areas in the white matter with dilation of ventricles and subarachnoid spaces [2], [8]), magnetic resonance imaging has become the primary imaging technique for the detection of central nervous system abnormalities. Hyperintense white matter lesions, dilated perivascular spaces, atrophy, hydrocephalus, cystic cribriform changes in white matter, subtle cerebellar atrophy, dilatation of venous sinuses, thickening of the diploë, and spinal canal stenosis have been described. However, the severity of the magnetic resonance imaging findings is unrelated to the severity of the clinical phenotype [9]. Such was the case with the present patient, who had fairly severe magnetic resonance imaging findings despite a relatively mild clinical course.

Section snippets

Case Report

This 5-year-old boy, the product of an uncomplicated full-term pregnancy and delivery, had normal early development. By age 2½, however, there were concerns about development difficulties (particularly lack of language acquisition), and in the last 6 months prior to presentation at our clinic the patient showed true regression.

On physical examination, the patient's weight and height were both at approximately the 75th percentile. His head circumference was greater than the 95th percentile for

Discussion

Sanfilippo syndrome is reported to have subtle magnetic resonance imaging findings early in the course of the disease. In the present case, however, the patient had only mild clinical manifestations of the disease, and the magnetic resonance imaging findings were the key to establishing the correct diagnosis. Neither the presentation nor the physical exam early on suggested a mucopolysaccharidosis as the diagnosis. In profoundly affected patients, delayed development is often noticed at 2 to 3

Conclusions

Magnetic resonance imaging findings raised the possibility of mucopolysaccharidosis in a patient with nonspecific developmental delay and mildly dysmorphic features. Cystic changes (dilated perivascular spaces) in the corpus callosum, basal ganglia, and white matter on magnetic resonance imaging should raise the possibility of a mucopolysaccharidosis, especially if seen in association with high-intensity signal in the white matter on T2-weighted images, enlargement of supratentorial external

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