Autism spectrum disorder in a child with propionic acidemia.

Autism is a neurodevelopmental disorder characterized by a combination of reciprocal social deficits, communication impairment, and rigid ritualistic interests. While autism does not have an identifying cause in most of the cases, it is associated with known medical conditions in at least 10% of cases. Although uncommon, cases of autism have also been reported in association with metabolic disorders. In this brief report, we describe the occurrence of autism in a 7-year-old girl with propionic acidemia (PA), a common form of organic aciduria resulting from the deficiency of propionyl-CoA carboxylase and characterized by frequent and potentially lethal episodes of metabolic acidosis often accompanied by hyperammonemia. It is particularly common in countries with high rates of consanguinity. Early diagnosis of autism in patients with metabolic disorders is important since autistic features are sometimes the most disruptive of all the child's problems. This facilitates providing the needed behavioral services not otherwise available for children with metabolic disorders.

The michigan autism spectrum questionnaire: a rating scale for high-functioning autism spectrum disorders.

Although the DSM-5 has recently created a single category of autism spectrum disorder (ASD), delineation of its putative subtypes remains clinically useful. For this process, screening instruments should ideally be brief, simple, and easily available. The aim of this study is to describe the validity of one such instrument. We administered the Michigan Autism Spectrum Questionnaire (MASQ), a 10-item questionnaire, to 42 patients with ASD (age range 6-13 years, mean 9.7 years, SD 2.5, one female) and 18 patients with other psychiatric disorders (age range 6-17 years, mean 11.7 years, SD 3.8, 6 females). Responses to each item were scored from 0 to 4 yielding a total score of 30. Patients with intellectual disability were excluded. As a group, patients with ASD scored higher than those with other psychiatric disorders (Chi-square test with 1 df = 16.019, P < 0.0001). Within the ASD group, a linear discriminant analysis found that the best cut-off points were 22 or above for Asperger syndrome, 14 to 21 for autism/PDDNOS, and less than 14 for those with other psychiatric disorders. We propose that the MASQ can be used as a brief measure to screen high-functioning ASD from other psychiatric disorders and to identify its possible subtypes.

Autism spectrum disorder and Klinefelter syndrome.

BACKGROUND: Autism is a severe handicapping disorder of early childhood characterized by a distinct pattern of social and communication impairment with rigid ritualistic interests. In about 10-25% of cases, it is associated with known medical conditions. Population-based studies of autism have found that Klinefelter's syndrome (KS), a common chromosome abnormality, is sometimes associated with autism. However, few detailed case descriptions of patients with KS and autism have not been published. CASE REPORT: In this paper, we describe the occurrence of autistic features in two cases of Klinefelter syndrome, one with the typical XXY karyotype and the other with the XXYY variant. CONCLUSION: Autistic features may be more common in persons with Klinefelter syndrome than generally believed. We propose that all patients with KS should be screened for the presence of autism.

Catatonia in autism: a distinct subtype?

Catatonia is a life-threatening disorder characterized by motor abnormalities, mutism, and disturbances of behaviour, which is increasingly being diagnosed in persons with autism. In this report, we describe the presentation and course of catatonia in an adolescent with autism who responded to electroconvulsive therapy (ECT). The illness started with depressive symptoms, but the predominant feature was one of extreme obsessive slowing and immobility. We propose that catatonia should be ruled out as a cause of regression sometimes seen in adolescents with autism, and that catatonia of autism may index a distinct subtype with a particularly poor outcome.

Autistic symptoms following herpes encephalitis.

Autism is a childhood onset neurodevelopmental disorder characterized by reciprocal social deficits, communication impairment, and rigid ritualistic interests, with the onset almost always before three years of age. Although the etiology of the disorder is strongly influenced by genes, environmental factors are also important. In this context, several reports have described its association with known medical conditions, including infections affecting the central nervous system. In this report, we describe an 11-year-old Asian youngster who developed the symptoms of autism following an episode of herpes encephalitis. In contrast to previous similar reports, imaging studies suggested a predominant involvement of the frontal lobes. At follow-up after three years, he continued to show the core deficits of autism. This case further supports the role of environmental factors, such as infections, in the etiology of autism, and suggests that in a minority of cases, autistic symptoms can develop in later childhood.

Autism in Down's syndrome: a family history study.

Several recent reports have described the occurrence of autism in subjects with Down's syndrome (DS). However, relatively little is known about the family history of these subjects, especially with reference to autism. In order to address this issue, the present author examined 11 subjects with DS and autism (DSM-III-R; nine males), and compared them with seven controls with DS but without autism (DSM-III-R; three males). Details about family psychiatric history were obtained from both groups with an emphasis on autism and related disorders. Subjects with both DS and autism had an excess of first-degree relatives who met the description of the broader phenotype of autism. Seven (64%) of the subjects with autism had an affected parent as against one (14%) of the control group. Similarly, four out of 11 siblings (36%) in the DS with autism group showed features suggestive of the broader autistic phenotype compared to none in the control group. These findings suggest that, at least in some cases, autism-specific genetic factors may be important even when autism occurs in the presence of known medical conditions. Further studies of the mechanism of comorbidity of autism with medical conditions may help clarify the aetiology of the disorder.

Serotonin dysregulation in adolescents with major depression: hormone response to meta-chlorophenylpiperazine (mCPP) infusion.

This study examined central serotonin disturbance, as reflected by neuroendocrine hormones, among adolescents with major depression. Prolactin, cortisol, and growth hormone were measured following the infusion of a serotonin agonist, meta-chlorophenylpiperazine (mCPP). Twelve (M=6, F=6) medication-free adolescents with major depression (MDD) were compared with 12 (M=6, F=6) matched normal control subjects, ranging in age from 13 to 17 years. Baseline evaluations and a battery of laboratory tests were completed. mCPP, 0.1 mg/kg i. v., was administered in a placebo-controlled design. Analyses of the neuroendocrine hormones revealed that the depressed group had a higher baseline prolactin level and an augmented prolactin response to mCPP challenge than did the control group. The depressed group experienced a sharper baseline-cortisol decline between 08.00 and 11.00 h, and compared to control subjects they displayed an augmented response to the challenge. The depressed group reported more side effects than the control group during saline infusion, but not during mCPP infusion. Findings suggest that depressed adolescents have an elevated baseline prolactin level, and also experience enhanced prolactin and cortisol responses to the serotonergic challenge. These preliminary findings will be confirmed during our ongoing study.

Anxiety contributes to suicidality in depressed adolescents.

Several studies have suggested a positive association between anxiety symptoms and suicidality in adults. However, relatively little is known about this topic in adolescents. To investigate this issue, we examined a group of adolescents admitted to our psychiatric inpatient unit. Fifty-six adolescents (mean age = 14.8 +/- 1.4; females = 34, males = 22; race = 95% Caucasians) participated in the study. Diagnoses were made using the DSM-III-R criteria and a diagnostic interview. Anxiety was found to significantly correlate with depression (r = .60; P = < .05) and suicidality (r = .72; P < .05). A multiple regression analysis revealed that anxiety and depression together accounted for more than half (55%) of the variance in suicidal ideation [F(2,46) = 28.4; P < .0001]. In addition, anxiety had an independent ability to predict suicidality (t = 5.01; P < .0001). Self-rated but not clinician-rated suicidality was positively correlated with both anxiety and depression. Clinical and research implications of these findings are discussed.

Is megalencephaly specific to autism?

Several recent reports have described the presence of increased head circumference (megalencephaly) in patients with autism. Although some studies have described reports of megalencephaly in other disorders such as schizophrenia in adults, few such studies have been performed in children and adolescents. In the present study, the authors compared 20 subjects with autism/ pervasive developmental disorder (DSM-IV; all males; mean age = 10.9 years) with 20 controls with attention deficit hyperactivity disorder (DSM-IV; all males; mean age = 11.1 years). Four subjects and five controls had evidence of megalencephaly. In addition to their core symptoms, the autistic subjects with megalencephaly were hyperactive and impulsive. These findings suggest that megalencephaly may not be specific to autism, and when present, it may index the presence of additional symptoms such as hyperactivity and impulsivity.

Deletion of chromosome 2q37 and autism: a distinct subtype?

Several reports have described the occurrence of chromosome abnormalities in autism, a neuro-developmental disorder characterized by social deficits, communication impairment, and a restricted range of interests. These include the fragile X abnormality and 15q duplications. In this report, we describe two cases of chromosome 2q37 and review the literature on this topic. We propose that deletion of the distal portion of the long arm of chromosome 2 (2q37) may be associated with some cases of autism and with a distinct phenotype. Increased awareness of the dysmorphic features associated with 2q37 deletions may aid in the molecular genetic analysis of this chromosome anomaly and clarify its relationship with autism.

Electroconvulsive treatment of a bipolar adolescent postcraniotomy for brain stem astrocytoma.

This is the first reported use of electroconvulsive treatment (ECT) in an adolescent with bipolar mania who had been treated with craniectomy for an intracranial neoplasm. The reported case is of a 16-year-old girl with a history of brain stem glioma (pontomesencephalic astrocytoma) diagnosed at 13 years of age. She presented in a psychiatric emergency room with suicidal ideation, depressed mood, irritability, olfactory hallucinations, early insomnia, grandiosity, and guilt. Her symptoms failed to respond to a trial of an antidepressant, mood stabilizer alone, and mood stabilizer in conjunction with a neuroleptic. The decision to use ECT was based on suicidal ideation, extreme disinhibition, and danger to self and others. Significant improvement in mood and remission in psychosis were noted after the eighth treatment. Comparison of 2-week pre-ECT and 3-month post-ECT cognitive testing revealed no change in IQ. This report highlights rapid response and the ability to tolerate ECT in an adolescent diagnosed with bipolar disorder, who had also been treated with radiation and craniotomy.

Medication noncompliance in adolescents with psychiatric disorders.

The purpose of the study was to estimate prevalence of medication noncompliance among adolescents, following discharge from hospital. A second purpose was to identify predictors of such noncompliance. Seventy-one adolescents, who had been prescribed a medication during psychiatric hospitalization, were interviewed by telephone, 6-8 months post-hospitalization. Medication noncompliance was defined as discontinuing medication without the recommendation of the treating physician. Twenty-four subjects (33.8%) were noncompliant with medication. Age, race, gender, SES, diagnosis, type and number of medications, severity of depression, and family living arrangement did not predict noncompliance. We concluded that noncompliance with psychotropic medications was relatively common and difficult to predict in adolescents who had been hospitalized to a psychiatric inpatient unit; the majority of them suffered from depression. Clinicians should be aware that medication noncompliance may be common and a relatively unpredictable phenomenon.

Comorbidity of Asperger syndrome: a preliminary report.

Asperger syndrome (AS) is a pervasive developmental disorder characterized by autistic social dysfunction and idiosyncratic interests in the presence of normal intelligence. There is no history of language delay. Although people with AS are known to suffer from comorbid psychiatric conditions, few studies have systematically addressed this topic. This preliminary report describes the occurrence of psychiatric disorders in a series of patients with AS diagnosed according to the ICD-10/DSM-IV criteria. Out of 35 patients (29 males and six females; mean age 15.1 years; mean verbal IQ 105.9; mean performance IQ 97.5; mean full-scale IQ 102.7), 23 patients (65%) presented with symptoms of an additional psychiatric disorder at the time of evaluation or during the 2-year follow-up. Children were most likely to suffer from attention deficit hyperactivity disorder, while depression was the most common diagnosis in adolescents and adults. The implications of these findings are discussed.

Depression in children with autism/pervasive developmental disorders: a case-control family history study.

Limited information is available about the occurrence of depression in children with autism and other pervasive developmental disorders (PDD). Although depression has been described in autistic children, questions about its validity have often been raised. One approach to address this issue is to investigate family histories of those autistic children diagnosed with clinical depression. Based on data available in nonautistic children, autistic children with depression would be expected to show an increased family history of depression. Since studies of this nature have not been attempted in autistic children, we compared the family history of 13 autistic/PDD children with depression (11 male; 2 female; M full-scale IQ 86.2, SD 24.2; M age 10.4 years, SD 2.2) with 10 autistic/PDD children without a history of current or previous depression (9 male; 1 female; M full-scale IQ 67, SD 12.9; M age 10.5 years, SD 1.6). Diagnosis of depression was based on the DSM-III-R criteria and confirmed independently by two psychiatrists. Ten (77%) of the depressed children had a positive family history of depression compared to 3 (30%) of the nondepressed group, t(21)=-2.4; p=.02. These findings lend support to the validity of depression as a distinct condition in some children with autism/PDD and suggest that, as in the normal population, autistic children who suffer from depression are more likely to have a family history of depression.

Chromosomes in autism and related pervasive developmental disorders: a cytogenetic study.

Few studies have examined the occurrence of chromosome abnormalities in a large sample of patients with autism and related pervasive developmental disorders (PDDs). In the present report, the authors examined a consecutive series of 92 children with PDDs (DSM-III-R; 75 males and 17 females). A cytogenetic examination, including growth in folate deficient medium, was performed in all cases. Three patients (3.2%) (two females and one male) showed chromosome abnormalities: deletion of the long arm of chromosome 8; tetrasomy of chromosome 15; and XYY syndrome. Only the subject who had tetrasomy 15 met the criteria for autistic disorder, while the other were diagnosed as suffering from a PDD not otherwise specified (PDDNOS). Another patient showed an abnormal fragile site at Xq27 in three out of 100 cells. However, subsequent molecular studies did not confirm the presence of fragile-X syndrome. These results suggest that chromosome abnormalities are uncommon in traditional autism and may be relatively more common in people with PDDNOS.

Clumsiness in autism and Asperger syndrome: a further report.

Clumsiness has been proposed as a diagnostic feature of Asperger syndrome (AS), a type of pervasive developmental disorder recently introduced in the ICD-10 and DSM-IV. However, the extent to which this symptom is specific to AS is not clear. To investigate this issue, we compared a sample of AS children with age- and sex-matched groups of children with autistic disorder and pervasive developmental disorder not otherwise specified (PDDNOS). Twelve subjects with AS (ICD-10/DSM-IV; 11 males; average age 11.4 years; mean full-scale IQ 104.9) were compared with 12 subjects with autistic disorder (DSM-III-R; II males; average age 10.3 years; mean full-scale IQ 78.4) and 12 subjects with PDDNOS (DSM-III-R; 10 males; average age 10.1 years; mean full-scale IQ 78.2). The BruininksOseretsky test, a standardized test of motor coordination, was administered blind by the same investigator to all the three groups. While coordination deficits were found in all three groups, children with AS were found to be less impaired than those with autistic disorder and PDDNOS. However, no significant relationship was found between coordination scores and diagnosis after adjusting for the level of intelligence. These findings suggest that some patients with AS may be less clumsy than those with autistic disorder and that this difference may be the result of their higher level of intelligence. Studies based on larger samples using multiple measures of coordination are needed to further clarify the role of clumsiness in the classification of pervasive developmental disorders.

Circulating autoantibodies to neuronal and glial filament proteins in autism.

Autoimmunity may be a pathogenic factor in autism, a behavioral disorder of early childhood onset. Circulating autoantibodies are produced in organ-specific autoimmunity; therefore, we investigated them in the plasma of autistic subjects, mentally retarded (MR) subjects, and healthy controls. Autoantibodies (IgG isotype) to neuron-axon filament protein (anti-NAFP) and glial fibrillary acidic protein (anti-GFAP) were analyzed by the Western immunoblotting technique. We found a significant increase in incidence of anti-NAFP (P = .004) and anti-GFAP (P = .002) in autistic subjects, but not in MR subjects. Clinically, these autoantibodies may be related to autoimmune pathology in autism.

Autism in Down's syndrome: family history correlates.

Although the association of autism with Down's syndrome is said to be uncommon, several reports have described the co-occurrence of the two disorders. This report describes three additional cases of Down's syndrome with autism. In all the patients, a history suggestive of the broader phenotype of autism was obtained in parents. This suggests that familial factors specific to autism may play an important role even when autism complicates a known medical condition such as Down's syndrome.

Integration of a sexuality counseling service into a reproductive health program for persons with mental retardation.

A socialization and sexuality counseling program was instituted as an integral part of a gynecologic service begun at the University of Michigan for persons with mental retardation. One hundred three patients were seen between 1986 and 1989 for counseling. Patients were referred for a variety of reasons, the most common being sexual behavior deemed inappropriate by the referring agent (i.e., direct care givers, parents, teachers, workshop supervisors, and other community professionals). Other concerns included sexual abuse, sterilization requests, sexuality and socialization education, marital questions, pregnancy assistance, abortion counseling, and family stress. Treatment techniques included gynecologic examination and follow-up, psychosexual education, psychiatric evaluation and follow-up, and group and individual psychosexual counseling. A majority of the patients improved during treatment. It is proposed that such a counseling program can play a useful role in the preparation of people with mental retardation to live in their communities as they deal with day-to-day decision making and should be an integral part of reproductive health care for this population.