Lysosomal diseases are characterized by the accumulation of large undegraded substances in the lysosomes of cells of the body, causing a number of clinical abnormalities in various districts as central nervous system, bones, and skin. They all lead to marked craniofacial dysproportion, and the term “gargoyle” has been frequently used to sketch faces of these children, resembling the grotesque decorations of many buildings in Italy, France, Belgium, Greece, and Egypt. These sculptures in limestone or marble were firstly conceived as water drainpipes or gutters acting as rainsprouts, and their name is due to the “gurgling” sound of water, which went across them [1]. They were often depicted as monkeyish creatures, pygmy dragons, or combinations of real animals and humans and placed on mansions or as ornaments over fountains, rooftops (cover picture), medieval doorways, under balconies (Fig. 1), and near spires of Gothic cathedrals, where they were believed to scare off evil spirits. In 1974, Autio et al. used the term “gargoyle” to describe the facial appearance of a child with aspartylglycosaminuria who resembled those decorations [2]. Besides myths and legendary creatures, the observation of living subjects with inborn errors of metabolism having pathological facial features might have served as inspiration for such sculptures. Although gargoyle-like features have been reported in many lysosomal diseases as I-cell disease (caused by the deficiency of multiple acid hydrolases), disorders of glycoprotein degradation (sialidosis, fucosidosis), and GM1 gangliosidosis (caused by β-galactosidase deficiency), gargoyles are classically associated with lysosomal diseases involving glycosaminoglycan catabolism, named mucopolysaccharidosis (MPS). The Scottish physician Charles Hunter and the Dutch pediatrician Gertrud Hurler described the first two forms of MPS, respectively, in 1917 and 1919, whereas the American Sylvestor Sanfilippo described the most complex form of MPS at a neuropsychiatric level in 1963. In all these diseases, there is a grotesque facial appearance because of the progressive lysosomal glycosaminoglycan deposits. Hurler syndrome is an autosomal recessive disorder caused by deficiency of α-L-iduronidase, displaying heterogeneous phenotypes with hydrocephalus, severe neurodevelopment delay, somatic regression, skeletal deformities, macrocrania, thickened calvarium, premature closures of lambdoid and sagittal sutures, shallow orbits, abnormal spacing of the teeth, and coarse facies. Hunter syndrome is caused by iduronate sulfatase deficiency, inherited with an X-linked recessive pattern, and characterized by moderate to severe communicating hydrocephalus and chronic papilledema. Sanfilippo syndrome is an autosomal recessive disorder caused by the deficiency of four specific enzymes leading to severe central nervous system degeneration and deterioration of social/adaptive skills [3]. Childs Nerv Syst (2007) 23:365–366 DOI 10.1007/s00381-007-0301-1