Mucopolysaccharidoses: early diagnostic signs in infants and children

Abstract

Mucopolysaccharidoses (MPS) comprise a group of lysosomal disorders that are characterized by progressive, systemic clinical manifestations and a coarse phenotype. The different types, having clinical, biochemical, and genetic heterogeneity, share key clinical features in varying combinations, including joint and skeletal dysplasia, coarse facial features, corneal clouding, inguinal or abdominal hernias, recurrent upper respiratory tract infections, heart valve disease, carpal tunnel syndrome, and variable neurological involvement. In the severe forms, these features usually appear in the first months of life, but a correct diagnosis is often reached later when suggestive signs are manifest. All MPS types may have severe or attenuated presentations depending on the residual enzymatic activity of the patient. Based on data from the literature and from personal experience, here we underline the very early signs of the severe forms which should alert the paediatrician on their first appearance. A few early signs are typical of MPS (i.e. gibbus) while many are unspecific (hernias, upper airway infections, organomegaly, etc.), and finding the association of many unspecific signs might prompt the paediatrician to search for a common cause and to carefully look for other more specific signs (gibbus and other skeletal deformities, heart murmur). We stress the need to increase awareness of MPS among paediatricians and other specialists to shorten the still existing diagnostic delay. A timely diagnosis is mandatory for the commencement of treatment as soon as possible, when available, to possibly obtain better results.

Keywords: Early MPS signs; Early MPS symptoms; Early-onset MPS; MPS; Mucopolysaccharidosis.

Fig. 1

MPS IH in 1-year-old patient. Coarse facies: flat nasal bridge, macroglossia, frontal bossing

Fig. 2

MPS IH. a Gibbus in a 9-month-old patient. b Spine x-ray of the spine in a 3-year-old patient. c T2-weighted magnetic resonance image of the spine showing significant kyphosis and vertebral canal stenosis

Fig. 3

MPS IH. X-ray evidence of dysostosis multiplex. a Thickening of the ribs in a 3-year-old patient and b hip dysplasia in another patient aged 18 months

Fig. 4

MPS IH: a Claw hand in an 18 month-old patient; b hand X-ray.

Fig. 5

MPS IH. a Thickening of the cortical bone of the skull and abnormal “J-shaped” conformation of the sella turcica. Dilatation of the periventricular spaces in b FLAIR and c T-2 weighted magnetic resonance images of a patient aged 17 months

Fig. 6

MPS II. A 3-year-old patient with only mild characteristic facial features

Fig. 7

MPS IIIA. The same patient at a 2.5 and b 5 years old. Note the different face expression, showing progression of the neurological impairment

Fig. 8

MPS IVA. a 4 year-old patient with b antero-posterior and c lateral x-rays showing “paddle-shaped” ribs and flattened and rounded vertebrae with a typical “anterior beaking” aspect

Fig. 9

MPS VI. A 2-year-old boy with evident coarse face and skeletal dysostosis