LAUSR

Childhood Disintegrative Disorder (CDD), also known as Heller’s syndrome and disintegrative psychosis, is a rare progressive neurological disorder, characterized by a late onset ([2 years of age) and regression of language, social function, and motor skills [1]. Based on 4 surveys of CDD from different countries, the pooled estimate for the prevalence of CDD is 0.17/10,000, 600 times less prevalent than autism [2]. CDD is characterized by an onset between 3 and 4 years of age after a period of apparently normal development; a severe regression with the progressive loss or marked impairment of spoken language, loss of play, loss of social skills, and loss of bowel and bladder control; a prodromal period of behavioral disruption with extreme agitation, fearfulness, and possible hallucinations, and a poor outcome with severe intellectual deterioration. CDD was first described by Thomas Heller in 1908. However, the definition has continued evolving over the past century, perhaps because of the rarity and lack of explanation for the condition. Initially, CDD was considered strictly a medical disorder and was believed to have identifiable medical causes. However, no specific medical or neurological cause has been found to account for all occurrences of the disorder by investigators who reviewed the reported cases [3]. Should CDD be considered a distinct diagnosis? Under the proposed DSM-5 revisions, all pervasive developmental disorders, including CDD, will be subsumed under the single diagnostic category of autism spectrum disorders. The rationale for this is the similarity between these disorders, as it is now thought that their symptoms place them on a continuum with autism. Thus, CDD is also considered a low-functioning form of autistic spectrum disorder [3]. Interestingly, mucopolysaccharidosis III (MPS III) is a rare genetic disease characterized by progressive cognitive decline and severe hyperactivity, with an onset between 2 and 6 years of age. Moreover, patients are often initially misdiagnosed as autism spectrum disorders, idiopathic developmental delay, attention deficit/hyperactivity disorder, or combinations of these, placing them at risk for unnecessary testing and treatments [4, 5]. Clinically, MPS III is composed of four different subtypes, each of which is caused by a deficiency in a different enzyme in the catabolic pathway of heparan sulfate, a type of glycosaminoglycan (GAG). All four subtypes are inherited in an autosomal recessive pattern. Collectively, the reported incidence of MPS III varies between 0.28 and 4.1 per 100,000 live births [6]. Electronic supplementary material The online version of this article (doi:10.1007/s12264-017-0119-0) contains supplementary material, which is available to authorized users.