Diagnostic Considerations

In addition to the differential diagnosis (see below), other problems to be considered include the following:

Intellectual disability (idiopathic or due to a known cause, such as lead poisoning, aminoacidopathy, iodine deficiency, or hypothyroidism)
Brain tumor
Heavy metal intoxication
Insecticide overdose
Long-chain or medium-chain fatty acidopathy
Neurodegenerative disorders
Psychoactive substance poisoning
Seizure disorder
Unusual presentation of neurologic manifestation of
HIV/AIDS, Landau-Kleffner syndrome (LKS), or adrenoleukodystrophy
Rett syndrome
Schilder syndrome or other progressive central nervous system (CNS) storage or metabolic disorders
Aminoacidurias
MECP2 gene mutations
Semantic pragmatic syndrome
Multidimensional impairment
Hydrocephaly
Pathologic demand avoidance (PDA) syndrome
Nonverbal learning disorder
Teratogenicity^[16]
Catatonia: In situations in which symptoms of catatonia are present (silence [mutism], tenseness and rigidity [holds back acts that are compelled by memories], refusal to obey commands, and displacing rising emotions and tension into motor acts that shut out reality [posturing, grimacing, staring, stereotypes]) and that appear to worsen or not respond to other medications, treatment with benzodiazepines should be considered. If a positive response occurs, the diagnosis of catatonia should be included in the differential diagnosis, especially because a state of extreme excitement can cause potentially fatal medical illness such as pneumonia, blood clotting problems (thrombosis), malnutrition or dehydration, concussion (due to head banging), or other cutaneous infection due to self-injurious behaviors while catatonic.^[37]

Differential Diagnoses

Anti-NMDA-receptor encephalitis
Mercury Toxicity

Workup

Barone R, Sturiale L, Fiumara A, Palmigiano A, Bua RO, Rizzo R, et al. CSF N-glycan profile reveals sialylation deficiency in a patient with GM2 gangliosidosis presenting as childhood disintegrative disorder. Autism Res. 2016 Apr. 9 (4):423-8. [QxMD MEDLINE Link].
Volkmar FR, State M, Klin A. Autism and autism spectrum disorders: diagnostic issues for the coming decade. J Child Psychol Psychiatry. 2009 Jan. 50(1-2):108-15. [QxMD MEDLINE Link].
Palomo R, Thompson M, Colombi C, Cook I, Goldring S, Young GS, et al. A case study of childhood disintegrative disorder using systematic analysis of family home movies. J Autism Dev Disord. 2008 Nov. 38(10):1853-8. [QxMD MEDLINE Link].
Rossignol DA, Rossignol LW, Smith S, Schneider C, Logerquist S, Usman A, et al. Hyperbaric treatment for children with autism: a multicenter, randomized, double-blind, controlled trial. BMC Pediatr. 2009 Mar 13. 9:21. [QxMD MEDLINE Link]. [Full Text].
Fombonne E. Epidemiology of pervasive developmental disorders. Pediatr Res. 2009 Jun. 65(6):591-8. [QxMD MEDLINE Link].
Libbey JE, Coon HH, Kirkman NJ, Sweeten TL, Miller JN, Stevenson EK, et al. Are there enhanced MBP autoantibodies in autism?. J Autism Dev Disord. 2008 Feb. 38(2):324-32. [QxMD MEDLINE Link].
Gottesman II, Gould TD. The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry. 2003 Apr. 160(4):636-45. [QxMD MEDLINE Link].
Berry-Kravis E, Sumis A, Hervey C, Nelson M, Porges SW, Weng N, et al. Open-label treatment trial of lithium to target the underlying defect in fragile X syndrome. J Dev Behav Pediatr. 2008 Aug. 29(4):293-302. [QxMD MEDLINE Link].
Jyonouchi H, Geng L, Streck DL, Toruner GA. Immunological characterization and transcription profiling of peripheral blood (PB) monocytes in children with autism spectrum disorders (ASD) and specific polysaccharide antibody deficiency (SPAD): case study. J Neuroinflammation. 2012 Jan 7. 9:4. [QxMD MEDLINE Link]. [Full Text].
Strug LJ, Clarke T, Chiang T, Chien M, Baskurt Z, Li W, et al. Centrotemporal sharp wave EEG trait in rolandic epilepsy maps to Elongator Protein Complex 4 (ELP4). Eur J Hum Genet. 2009 Sep. 17(9):1171-81. [QxMD MEDLINE Link]. [Full Text].
Ortega-Hernandez OD, Kivity S, Shoenfeld Y. Olfaction, psychiatric disorders and autoimmunity: is there a common genetic association?. Autoimmunity. 2009 Jan. 42(1):80-8. [QxMD MEDLINE Link].
Lillywhite LM, Saling MM, Harvey AS, Abbott DF, Archer JS, Vears DF, et al. Neuropsychological and functional MRI studies provide converging evidence of anterior language dysfunction in BECTS. Epilepsia. 2009 Oct. 50(10):2276-84. [QxMD MEDLINE Link].
Posey DJ, Erickson CA, McDougle CJ. Developing drugs for core social and communication impairment in autism. Child Adolesc Psychiatr Clin N Am. 2008 Oct. 17(4):787-801, viii-ix. [QxMD MEDLINE Link]. [Full Text].
Gupta AR, Westphal A, Yang DYJ, Sullivan CAW, Eilbott J, Zaidi S, et al. Neurogenetic analysis of childhood disintegrative disorder. Mol Autism. 2017. 8:19. [QxMD MEDLINE Link].
Thurm A, Powell EM, Neul JL, Wagner A, Zwaigenbaum L. Loss of skills and onset patterns in neurodevelopmental disorders: Understanding the neurobiological mechanisms. Autism Res. 2018 Feb. 11 (2):212-222. [QxMD MEDLINE Link].
Miller MT, Ventura L, Strömland K. Thalidomide and misoprostol: Ophthalmologic manifestations and associations both expected and unexpected. Birth Defects Res A Clin Mol Teratol. 2009 Aug. 85(8):667-76. [QxMD MEDLINE Link].
Tedrus GM, Fonseca LC, Melo EM, Ximenes VL. Educational problems related to quantitative EEG changes in benign childhood epilepsy with centrotemporal spikes. Epilepsy Behav. 2009 Aug. 15(4):486-90. [QxMD MEDLINE Link].
Watemberg N, Leitner Y, Fattal-Valevski A, Kramer U. Epileptic negative myoclonus as the presenting seizure type in rolandic epilepsy. Pediatr Neurol. 2009 Jul. 41(1):59-64. [QxMD MEDLINE Link].
Enstrom AM, Van de Water JA, Ashwood P. Autoimmunity in autism. Curr Opin Investig Drugs. 2009 May. 10(5):463-73. [QxMD MEDLINE Link].
Critchfield JW, van Hemert S, Ash M, Mulder L, Ashwood P. The potential role of probiotics in the management of childhood autism spectrum disorders. Gastroenterol Res Pract. 2011. 2011:161358. [QxMD MEDLINE Link]. [Full Text].
Finegold SM, Downes J, Summanen PH. Microbiology of regressive autism. Anaerobe. 2012 Apr. 18(2):260-2. [QxMD MEDLINE Link].
Jyonouchi H, Geng L, Ruby A, et al. Evaluation of an association between gastrointestinal symptoms and cytokine production against common dietary proteins in children with autism spectrum disorders. J Pediatr. 2005 May. 146(5):605-10. [QxMD MEDLINE Link].
Stigler KA, Posey DJ, McDougle CJ. Ramelteon for insomnia in two youths with autistic disorder. J Child Adolesc Psychopharmacol. 2006 Oct. 16(5):631-6. [QxMD MEDLINE Link].
Malhotra S, Subodh BN, Parakh P, Lahariya S. Brief report: childhood disintegrative disorder as a likely manifestation of vitamin B12 deficiency. J Autism Dev Disord. 2013 Sep. 43(9):2207-10. [QxMD MEDLINE Link].
Rosman NP, Bergia BM. Childhood disintegrative disorder: distinction from autistic disorder and predictors of outcome. J Child Neurol. 2013 Dec. 28(12):1587-98. [QxMD MEDLINE Link].
Creten C, van der Zwaan S, Blankespoor RJ, Maatkamp A, Klinkenberg S, van Kranen-Mastenbroek VH, et al. [Anti-NMDA-receptor encephalitis: a new axis-III disorder in the differential diagnosis of childhood disintegrative disorder, early onset schizophrenia and late onset autism]. Tijdschr Psychiatr. 2012. 54(5):475-9. [QxMD MEDLINE Link].
Verma JK, Mohapatra S. Childhood Disintegrative Disorder as a Complication of Chicken Pox. Indian J Psychol Med. 2016 Jan-Feb. 38 (1):65-6. [QxMD MEDLINE Link].
American Psychiatric Association. Childhood Disintegrative Disorder 299.10. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. 1994. 73-5.
Stigler KA, McDougle CJ. Pharmacotherapy of irritability in pervasive developmental disorders. Child Adolesc Psychiatr Clin N Am. 2008 Oct. 17(4):739-52, vii-viii. [QxMD MEDLINE Link].
Agarwal V, Sitholey P, Mohan I. Childhood Disintegrative Disorder, an atypical presentation: a case report. J Autism Dev Disord. 2005 Dec. 35(6):873-4. [QxMD MEDLINE Link].
Mordekar SR, Prendergast M, Chattopadhyay AK, Baxter PS. Corticosteroid treatment of behaviour, language and motor regression in childhood disintegrative disorder. Eur J Paediatr Neurol. 2008 Jul 13. [QxMD MEDLINE Link].
Russo M, Perry R, Kolodny E, Gillberg C. Heller syndrome in a pre-school boy. Proposed medical evaluation and hypothesized pathogenesis. Eur Child Adolesc Psychiatry. 1996 Sep. 5(3):172-7. [QxMD MEDLINE Link].
Akshoomoff N, Farid N, Courchesne E, Haas R. Abnormalities on the neurological examination and EEG in young children with pervasive developmental disorders. J Autism Dev Disord. 2007 May. 37(5):887-93. [QxMD MEDLINE Link].
Kurita H, Koyama T, Osada H. Comparison of childhood disintegrative disorder and disintegrative psychosis not diagnosed as childhood disintegrative disorder. Psychiatry Clin Neurosci. 2005 Apr. 59(2):200-5. [QxMD MEDLINE Link].
Young EC, Diehl JJ, Morris D, et al. The use of two language tests to identify pragmatic language problems in children with autism spectrum disorders. Lang Speech Hear Serv Sch. 2005 Jan. 36(1):62-72. [QxMD MEDLINE Link].
Shirazi E, Hosseinpoor S, Mirhosseini SM, Bidaki R. Childhood disintegrative disorder with seasonal total mutism: A rare clinical presentation. Adv Biomed Res. 2016. 5:30. [QxMD MEDLINE Link].
Gibson RC, Walcott G. Benzodiazepines for catatonia in people with schizophrenia and other serious mental illnesses. Cochrane Database Syst Rev. 2008 Oct 8. CD006570. [QxMD MEDLINE Link].
Cohen IL, Schmidt-Lackner S, Romanczyk R, Sudhalter V. The PDD Behavior Inventory: a rating scale for assessing response to intervention in children with pervasive developmental disorder. J Autism Dev Disord. 2003 Feb. 33(1):31-45. [QxMD MEDLINE Link].
Findling RL. Atypical antipsychotic treatment of disruptive behavior disorders in children and adolescents. J Clin Psychiatry. 2008. 69 Suppl 4:9-14. [QxMD MEDLINE Link].
Stigler KA, Diener JT, Kohn AE, Li L, Erickson CA, Posey DJ, et al. Aripiprazole in pervasive developmental disorder not otherwise specified and Asperger's disorder: a 14-week, prospective, open-label study. J Child Adolesc Psychopharmacol. 2009 Jun. 19(3):265-74. [QxMD MEDLINE Link].
King BH, Hollander E, Sikich L, McCracken JT, Scahill L, Bregman JD, et al. Lack of efficacy of citalopram in children with autism spectrum disorders and high levels of repetitive behavior: citalopram ineffective in children with autism. Arch Gen Psychiatry. 2009 Jun. 66(6):583-90. [QxMD MEDLINE Link].
Biederman J, Hammerness P, Doyle R, Joshi G, Aleardi M, Mick E. Risperidone treatment for ADHD in children and adolescents with bipolar disorder. Neuropsychiatr Dis Treat. 2008 Feb. 4(1):203-7. [QxMD MEDLINE Link]. [Full Text].
Posey DJ, Aman MG, McCracken JT, Scahill L, Tierney E, Arnold LE, et al. Positive effects of methylphenidate on inattention and hyperactivity in pervasive developmental disorders: an analysis of secondary measures. Biol Psychiatry. 2007 Feb 15. 61(4):538-44. [QxMD MEDLINE Link].
Carlson T, Reynolds CA, Caplan R. Case report: valproic Acid and risperidone treatment leading to development of hyperammonemia and mania. J Am Acad Child Adolesc Psychiatry. 2007 Mar. 46(3):356-61. [QxMD MEDLINE Link].
Chakraborty N, Johnston T. Aripiprazole and neuroleptic malignant syndrome. Int Clin Psychopharmacol. 2004 Nov. 19(6):351-3. [QxMD MEDLINE Link].
Chungh DS, Kim BN, Cho SC. Neuroleptic malignant syndrome due to three atypical antipsychotics in a child. J Psychopharmacol. 2005 Jul. 19(4):422-5. [QxMD MEDLINE Link].
Nielsen J, Bruhn AM. Atypical neuroleptic malignant syndrome caused by olanzapine. Acta Psychiatr Scand. 2005 Sep. 112(3):238-40; discussion 240. [QxMD MEDLINE Link].
Segura-Bruna N, Rodriguez-Campello A, Puente V, Roquer J. Valproate-induced hyperammonemic encephalopathy. Acta Neurol Scand. 2006 Jul. 114(1):1-7. [QxMD MEDLINE Link].
Soares-Fernandes JP, Machado A, Ribeiro M, et al. Hippocampal involvement in valproate-induced acute hyperammonemic encephalopathy. Arch Neurol. 2006 Aug. 63(8):1202-3. [QxMD MEDLINE Link].
Stewart JT. Treatment of valproate-induced hyperammonemia. J Am Geriatr Soc. 2005 Jun. 53(6):1080. [QxMD MEDLINE Link].
[Guideline] Kagan-Kushnir T, Roberts SW, Snead OC 3rd. Screening electroencephalograms in autism spectrum disorders: evidence-based guideline. J Child Neurol. 2005 Mar. 20(3):197-206. [QxMD MEDLINE Link].
Chez MG, Burton Q, Dowling T, Chang M, Khanna P, Kramer C. Memantine as adjunctive therapy in children diagnosed with autistic spectrum disorders: an observation of initial clinical response and maintenance tolerability. J Child Neurol. 2007 May. 22(5):574-9. [QxMD MEDLINE Link].
Leskovec TJ, Rowles BM, Findling RL. Pharmacological treatment options for autism spectrum disorders in children and adolescents. Harv Rev Psychiatry. 2008. 16(2):97-112. [QxMD MEDLINE Link].
Sonnier L, Barzman D. Pharmacologic management of acutely agitated pediatric patients. Paediatr Drugs. 2011 Feb 1. 13(1):1-10. [QxMD MEDLINE Link].
Levy SE, Hyman SL. Complementary and alternative medicine treatments for children with autism spectrum disorders. Child Adolesc Psychiatr Clin N Am. 2008 Oct. 17(4):803-20, ix. [QxMD MEDLINE Link]. [Full Text].
Duncan B, McDonough-Means S, Worden K, Schnyer R, Andrews J, Meaney FJ. Effectiveness of osteopathy in the cranial field and myofascial release versus acupuncture as complementary treatment for children with spastic cerebral palsy: a pilot study. J Am Osteopath Assoc. 2008 Oct. 108(10):559-70. [QxMD MEDLINE Link].
Nye C, Brice A. Combined vitamin B6-magnesium treatment in autism spectrum disorder. Cochrane Database Syst Rev. 2005 Oct 19. CD003497. [QxMD MEDLINE Link].
Murch S. Diet, immunity, and autistic spectrum disorders. J Pediatr. 2005 May. 146(5):582-4. [QxMD MEDLINE Link].
A Message From APA President Dilip Jeste, M.D., on DSM-5. Available at http://www.psychnews.org/files/DSM-message.pdf. Accessed: December 1, 2012.
Goin-Kochel RP, Trinh S, Barber S, Bernier R. Gene Disrupting Mutations Associated with Regression in Autism Spectrum Disorder. J Autism Dev Disord. 2017. Nov;47(11):3600-3607. [QxMD MEDLINE Link]. [Full Text].