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Neuroradiology Case of the Week

Case 107

Ruusu Ketonen, Leena Ketonen, MD, PhD, Ravinder Sidhu MD,
and Sudhir Kathuria, MD

Clinical Presentation: A 6-year-old female with Sanfilippo syndrome has been stable and interacting until 5 months ago, when she experienced rapid deterioration.

Radiological Findings: Sagittal T1WI images demonstrated an omega-shaped sella with a thin corpus callosum, and thick diploic space of skull vault (Fig. 1). Axial T2WI images showed diffuse volume loss which is more marked in occipital lobes (Fig. 2). Axial T2WI & FLAIR images revealed white matter abnormalities in frontal lobes (Figs. 3A&B).

Diagnosis: Sanfilippo syndrome

Discussion: 
     The Sanfilippo syndrome belongs to mucopolysaccharidosis (MPS) which is a family of lysosomal storage diseases. These result due to deficiencies in the enzymes required for the degradation of glycosaminoglycans (GAG). In Sanfilippo syndrome this defect results in an accumulation of heparan sulfate. This causes the distended lysosomes to accumulate and interfere with cell function.
     Sanfilippo syndrome or mucopolysaccharidosis III (MPS III) comprises of four subtypes. All are inherited in an autosomal recessive manner. Type A is the most common and also the most severe subtype. Other subtypes usually have milder clinical presentation than type A cases.
     Even though these subtypes are linked to different enzymes, their clinical picture is rather similar considering CNS involvement. The disease manifests in early childhood with severe developmental delay. The mental deterioration is progressive from the third year of life. The syndrome leads to death in the second decade. Unlike other MPS, there is little involvement of other tissues and organs besides the CNS. The diagnosis for the syndrome is usually confirmed by a marked excretion of heparan sulfate in urine and the absence of the specific enzyme in leukocytes, or fibroblasts.
      Patients with Sanfilippo syndrome usually demonstrate mild to moderate dysostosis multiplex where the hallmark features are malformation of the vertebral bodies, hyperostosis of the skull and widening of the metaphysis of the long bones with delayed ossification of the epiphysis.
     MR shows white matter abnormalities, which may include diffuse and focal areas of prolonged T1 and T2 relaxation times and reduced contrast between gray matter in the cortex and the underlying white matter. This is caused by deposition of GM3-ganglioside in neurons and astrocytes. Sometimes well-defined foci, isointense with CSF, are seen in the cerebral white matter. These multicystic (cribiform) structures are believed to represent buildup of mucopolysaccharides in perivascular spaces. The high signals are considered to be the result of demyelination, gliosis and increased fluid content. Ventricular enlargement and cortical atrophy are typical findings in the early stages of the disease. Other findings may include thickening of the diploe, callosal atrophy, arachnoid cysts and altered signal of thalamus and basal ganglia on T1 and T2-weighted images, giving a “honeycomb” resembling appearance.

References:

1. Zafeiriou DI, Savvopoulou-Augoustidou PA, Sewell A, et al. Serial magnetic resonance imaging findings in mucopolysaccharidosis IIIB (Sanfilippo's syndrome B). Brain Dev 2001; 6:385-9.
2. Barone R, Nigro F, Triulzi F, Musumeci S, Fiumara A, Pavone L. Clinical and neuroradiological follow-up in mucopolysaccharidosis type III (Sanfilippo syndrome). Neuropediatrics. Oct 1999; 30(5):270-4.
3. Zafeiriou D, Auggoustidou-Savvopoulou PA, Papadopoulou FA, et al. Magnetic resonance imaging findings in mild mucopolysaccharidosis II (Hunter's syndrome). Eur J Paediatr Neurol.1989;2(3):153-6.