An inborn error of metabolism with a deficiency of enzymes involved in heparan sulfate (HS) degradation. The affected infants appear normal at birth with slowing of development taking place at about one to two years, occasionally not becoming apparent until early school age. Behavioral disorders, mental deterioration, and a loss of motor skills are the principal features. Hirsutism, macrocephaly, and limited joint movements. Four types, each with a different enzyme deficiency, are recognized: A, B, C and D. The phenotype is similar in all four types and consists mainly of some facial coarsening with dull appearance, slightly sunken nasal bridge, and abundant scalp hair. Early development is usually normal, followed between the ages of 2 to 6 years by mainly behavioral disorders with progressive loss of mental and motor skills with spastic diplegia, the patient eventually becoming bedridden. Death usually takes place from 10 to 20 years of age. Type A has the most severe course with the earliest onset and mortality. Type A Synonyms: Sanfilippo syndrome A heparan sulfate sulfatase deficiency mucopolysaccharidosis IIIA (MPS IIIA) Caused by heparan sulfatase (EC 3.10.1.1) deficiency. Type B Synonyms: Sanfilippo syndrome B mucopolysaccharidosis IIIB (MPS IIIB) N-acetyl-alpha-D-glucosaminidase (NAG) deficiency N-acetyl-alpha-D-glucosaminidase (NAG) polymorphism] is caused by Caused by N-acetyl-alpha-D-glucosaminidase (EC 3.2.1.50) deficiency. Type C Synonyms: Sanfilippo syndrome C acetyl-CoA:alpha-glucosamide N-acetyltransferase deficiency mucopolysaccharidosis IIIC (MPS IIIC) Caused by acetyl-CoA:alpha-glucosamide N-acetyltransferase (EC 2.3.13) deficiency. Type D Synonyms: Sanfilippo syndrome D mucopolysaccharidosis IIID (MPS IIID) N-acetylglucosamine-6-sulfate sulfatase deficiency) C Caused by N-acetylglucosamine-6-sulfate sulfatase (3.1.6.14) deficiency.