CASE 5725 Published on 02.03.2007

Sanfilippo syndrome

Section

Musculoskeletal system

Case Type

Clinical Cases

Authors

Mornjakovic A, Catibusic F.

Patient

5 years, female

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Clinical History

A patient presented with macrocephaly, coarse facial features and deafness.

Imaging Findings

The mentally retarded young girl was referred to the Pediatric Clinic with macrocephaly, coarse facial features and deafness. Further examination disclosed clouding of the cornea, progenia, the small and widely spaced teeth, short neck, kyphosis of the spine near the toracolumbar junction, coxa vara,hepatosplenomegaly and signs of atrial septal defect. Radiographs of the skull, chest, thoracolumbal junction, hand and hips were performed and these findings were typical of mucopolysaccharidosis. In the present case heparitin sulfaturia was only found. Heparan sulphamidase activity was deficient in leukocytes.

Discussion

Mucopolysaccharidosis (MPS) type III or Sanfilippo syndrome was first identified by Meyer chemically in 1961 and it was studied clinically by Sanfilippo and his associates. They recognized that the mental retardation was unusually severe, but the somatic changes were relatively mild. An epidemiological study of the mucopolysaccharidoses in Western Australia using multiple ascertainment sources was carried out and the incidence rate for the period 1969 -1996 was estimated. An incidence of approximately 1 in 58,000 live births was obtained for MPS type III. The overall incidence for all types of mucopolysaccharidosis was approximately 1 in 29,000 live births. In this syndrome heparansulphate accumulates in the lysosomes because of an enzymatic disorder in mucopolysaccharides degradation. The result is the functional disorder of the involved tissues. The Sanfilippo syndrome is characterized by a combination of mental deterioration, hepatosplenomegaly and a typical facial appearance. Clouding of the cornea and signs of the cardiac disease were rare. Radiographic changes in the skeleton are similar to those in MPS type I (Hurler syndrome) but milder, with the most diagnostic slight findings in the hands, pelvis and spine. In some MPS type III patients, serum vitamin D is low and bone mineral density greatly reduced at lumbar and femoral sites, indicating the possibility of osteoporosis and osteomalacia. These skeletal effects probably result from nutritional deficiencies and inability to walk, rather than from the genetic defect itself. It is possible that in many of severely retarded children MPS is never detected. Physicians evaluating adults also must remain aware of possible new adult presentations of storage conditions. Therefore, the real role of the radiologist is to suggest the likelihood of one of these disorders, leaving it to geneticist to determine biochemically which dysplasia is precisely involved. The dysostosis multiplex group contains all the MPS, mucolipidoses (MLs)and multiple other “storage diseases” that produce a skeletal dysplasia. Currently there are 46 known conditions in this group.

Differential Diagnosis List

Sanfilippo syndrome (MPS type III)

Final Diagnosis

Sanfilippo syndrome (MPS type III)

References

[1] Nelson J, Crowhurst J, Carey B, Greed L. Incidence of the mucopolysaccharidoses in Western Australia. Am J Med Genet A. 2003 Dec;123(3):310-3. (PMID: 14608657)

[2] Rigante D, Caradonna P. Secondary skeletal involvement in Sanfilippo syndrome. QJM. 2004 Apr;97(4):205-9. (PMID: 15028850)

[3] Visser A, Vissink A. Syndromes 4. Sanfilippo syndrome. Ned Tijdschr Tandheelkd. 1998 Sep;105(9):324-5. (PMID: 1192844)

[4] Van Hove JL, Wevers RA, Van Cleemput J, et al. Late Onset visceral presentation with cardiomyopathy and without neurological symptoms of adult Sanfilippo syndrome. Am J Med Genet. 2003 May 1;118A (4):382-7. (PMID: 12687673)

[5] Di Natale P, Villani GR, Di Domenico C, et al. Analysis of Sanfilippo A gene mutations in a
large pedigree. Clin Genet. 2003Apr;63(4):314-8. (PMID: 12702166)

Case information

URL:	https://www.eurorad.org/case/5725
DOI:	10.1594/EURORAD/CASE.5725
ISSN:	1563-4086

Figure 1

Radiologic findings in a 5-year old girl with Sanfilippo syndrome (MPS type III)

1a: X-Ray, conventional Lateral X-ray of the skull showing enlarged neurocranium in anteroposterior diameter (22,3 cm) with thick calvarium especially of the posterior two-thirds of the skull vault (10 mm).

1b: X-Ray, conventional Pituitary fossa (large arrow) is elongated ventrodorsally into an omega - shape due to long recesses under the anterior clinoid processes.

1c: X-Ray, conventional Underdevelopment of the paranasal sinuses is present (large arrows).

1d: X-Ray, conventional Progenia due to the enlarged mandible (double arrow) and square mandibular condyles are present.

Figure 2

Chest X-ray

2a: X-Ray, conventional PA-chest radiograph showing spatulate ribs, relatively pinched at their vertebral ends but dilated at their sternal ends. The intercostal spaces are correspondingly narrowed. The medial halves of the clavicles are swollen. Mild cardiomegaly with a nonspecific silhouette related to atrial septal defect is present. The shadows of the enlarged liver and spleen are outlined.

Figure 3

Lumbar spine X-ray

3a: X-Ray, conventional Lateral X-ray of the lumbar spine showing slight hypoplasia of the body of T12 and L1 with their slight dislocation dorsad and beaking of their anterior margins.

Figure 4

Pelvis X-ray

4a: X-Ray, conventional The proximal ends of femora are bent into varus deformities. At about the level of the trochanters the femoral shafts begin to increase in girth. The pubic and ishial bones appear dilated. The bases of the ilia are not stenosed.

Figure 5

Hand X-ray

5a: X-Ray, conventional X-ray of the hand showing relative lack of waisting of the metacarpals (bottom arrow) especially the 5th metacarpal bone and relatively broad middle phalanges of the fingers (top arrow). Only two carpal osification centers are present, adequate to 1-year old child.