The yield of laboratory investigations in children with infantile autism

Kosinovsky, B.; Hermon, S.; Yoran-Hegesh, Roni; Golomb, Abigail; Senecky, Yehuda; Goez, Helly; Kramer, Uri

doi:10.1007/s00702-004-0198-8

Cited by 36 publications

(21 citation statements)

References 38 publications

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“…All of them have been performed on restricted cohorts of ASD patients. One study reported that none of the 53 patients with ASD, screened for ammonia, amino acids, lactic acid and pyruvic acid in blood and urinary organic acids, exhibited abnormal results [41]. Also, Wang et al .…”

Section: Discussionmentioning

confidence: 99%

Should Metabolic Diseases Be Systematically Screened in Nonsyndromic Autism Spectrum Disorders?

et al. 2011

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BackgroundIn the investigation of autism spectrum disorders (ASD), a genetic cause is found in approximately 10–20%. Among these cases, the prevalence of the rare inherited metabolic disorders (IMD) is unknown and poorly evaluated. An IMD responsible for ASD is usually identified by the associated clinical phenotype such as dysmorphic features, ataxia, microcephaly, epilepsy, and severe intellectual disability (ID). In rare cases, however, ASD may be considered as nonsyndromic at the onset of a related IMD.ObjectivesTo evaluate the utility of routine metabolic investigations in nonsyndromic ASD.Patients and MethodsWe retrospectively analyzed the results of a metabolic workup (urinary mucopolysaccharides, urinary purines and pyrimidines, urinary creatine and guanidinoacetate, urinary organic acids, plasma and urinary amino acids) routinely performed in 274 nonsyndromic ASD children.ResultsThe metabolic parameters were in the normal range for all but 2 patients: one with unspecific creatine urinary excretion and the other with persistent 3-methylglutaconic aciduria.ConclusionsThese data provide the largest ever reported cohort of ASD patients for whom a systematic metabolic workup has been performed; they suggest that such a routine metabolic screening does not contribute to the causative diagnosis of nonsyndromic ASD. They also emphasize that the prevalence of screened IMD in nonsyndromic ASD is probably not higher than in the general population (<0.5%). A careful clinical evaluation is probably more reasonable and of better medical practice than a costly systematic workup.

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Section: Discussionmentioning

confidence: 99%

Should Metabolic Diseases Be Systematically Screened in Nonsyndromic Autism Spectrum Disorders?

et al. 2011

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“…[16][17][18][19][20] This range is applicable even for evaluations of patients with pervasive developmental disorder not otherwise specified, atypical autism, Asperger syndrome, or autistic features who did not necessarily meet the criteria of the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders criteria for pervasive developmental disorder. 21 Many factors seem to influence the diagnostic yield.…”

Section: Reported Approaches and Yieldsmentioning

confidence: 99%

Clinical genetics evaluation in identifying the etiology of autism spectrum disorders: 2013 guideline revisions

Schaefer

Mendelsohn

2013

Genetics in Medicine

453

393

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Autism spectrum disorders (ASDs), also known as pervasive developmental disorders, are a behaviorally defined group of neurodevelopmental disorders that are usually diagnosed in early childhood. They are characterized by varying degrees of limitations in communication and social interaction and by atypical, repetitive behaviors with an onset before 3 years of age. The phenotype of ASDs is extremely heterogeneous, with differences from person to person in a wide range of symptoms and severity as well as differences between the various subtypes of ASDs (e.g., autistic disorder, Asperger syndrome, and pervasive developmental disorder not otherwise specified).Multiple lines of epidemiologic evidence support the strong role of genetics in the etiology of ASDs. 1-3 Results of population studies of unselected cases of autism are most consistent with multifactorial inheritance. Until quite recently, the accepted recurrence risk for full siblings of a child with autism has been in the range of 3-10%. [4][5][6] Overall, only 2-3% of families have more than one affected child (possibly because of voluntary avoidance of pregnancy after a child is diagnosed). Most studies have reported a sex bias in the recurrence risk in keeping with the presumption of a "multifactorial" mode of inheritance (higher risk if the affected person is of the less commonly affected sex). As such, the reported risk is 7% of another affected child if the first affected child is female and 4% if the first affected child is male. 7 If multiple children (two or more) have autism, the recurrence risk is on the order of 33-50% for any future pregnancy. 7 Two recent studies 8,9 have reported even higher recurrence risks of 11 and 19% with single-sibling involvement. The first 8 was a retrospective self-enrolled/self-identified study using an interactive website. The diagnosis was confirmed, but the identification of second siblings may be a source of ascertainment bias. The second 9 was an international multisite prospective study in 664 families with a calculated 19% recurrence risk. Interestingly, the typically reported sex bias was not noted in one of these studies. 8 Both were single studies that bear replication.The autism spectrum disorders are a collective of conditions that have in common impaired socialization and communication in association with stereotypic behaviors. The reported incidence of autism spectrum disorders has increased dramatically over the past two decades. In addition, increased attention has been paid to these conditions by both lay and professional groups. These trends have resulted in an increase in the number of referrals to clinical geneticist for the evaluation of persons with autism spectrum disorders. The primary roles of the geneticist in this process are to define etiology when possible, to provide genetic counseling, and to contribute to case management. In deciding on the appropriate evaluation for a particular patient, the geneticist will consider a host of factors: (i) ensuring an accurate diagnosis of autism befor...

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“…Fragile X syndrome (FXS) is the most common single gene cause of ASD, responsible for approximately 3% of autism cases (Kosinovsky et al 2005). The prevalence rate of ASD in FXS is estimated between 25% and 50%, depending on the criteria utilized (Clifford et al 2007; Garcia-Nonell et al 2008; Hatton et al 2006; Kaufmann et al 2004).…”

Section: Introductionmentioning

confidence: 99%

Impact of acamprosate on plasma amyloid-β precursor protein in youth: A pilot analysis in fragile X syndrome-associated and idiopathic autism spectrum disorder suggests a pharmacodynamic protein marker

Erickson

Ray

Maloney

et al. 2014

Journal of Psychiatric Research

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Background Understanding of the pathophysiology of autism spectrum disorder (ASD) remains limited. Brain overgrowth has been hypothesized to be associated with the development of ASD. A derivative of amyloid-β precursor protein (APP), secreted APPα (sAPPα), has neuroproliferative effects and has been shown to be elevated in the plasma of persons with ASD compared to control subjects. Reduction in sAPPα holds promise as a novel molecular target of treatment in ASD. Research into the neurochemistry of ASD has repeatedly implicated excessive glutamatergic and deficient GABAergic neurotransmission in the disorder. With this in mind, acamprosate, a novel modulator of glutamate and GABA function, has been studied in ASD. No data is available on the impact of glutamate or GABA modulation on sAPPα function. Methods Plasma APP derivative levels pre- and post-treatment with acamprosate were determined in two pilot studies involving youth with idiopathic and fragile X syndrome (FXS)-associated ASD. We additionally compared baseline APP derivative levels between youth with FXS-associated or idiopathic ASD. Results Acamprosate use was associated with a significant reduction in plasma sAPP(total) and sAPPα levels but no change occurred in Aβ40 or Aβ42 levels in 15 youth with ASD (mean age: 11.1 years). Youth with FXS-associated ASD (n=12) showed increased sAPPα processing compared to age-, gender- and IQ-match youth with idiopathic ASD (n=11). Conclusions Plasma APP derivative analysis holds promise as a potential biomarker for use in ASD targeted treatment. Reduction in sAPP (total) and sAPPα may be a novel pharmacodynamic property of acamprosate. Future study is required to address limitations of the current study to determine if baseline APP derivative analysis may predict subgroups of persons with idiopathic or FXS-associated ASD who may respond best to acamprosate or to potentially other modulators of glutamate and/or GABA neurotransmission.

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The yield of laboratory investigations in children with infantile autism

Cited by 36 publications

References 38 publications

Should Metabolic Diseases Be Systematically Screened in Nonsyndromic Autism Spectrum Disorders?

Should Metabolic Diseases Be Systematically Screened in Nonsyndromic Autism Spectrum Disorders?

Clinical genetics evaluation in identifying the etiology of autism spectrum disorders: 2013 guideline revisions

Impact of acamprosate on plasma amyloid-β precursor protein in youth: A pilot analysis in fragile X syndrome-associated and idiopathic autism spectrum disorder suggests a pharmacodynamic protein marker

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