Helena H. Ho

Subtypes of Autism by Cluster Analysis.

Multidisciplinary data from 166 children with autistic spectrum disorders were subjected to cluster analysis. Cross-validation between random halves of the sample showed acceptable consistency of the clustering method. Four clinically meaningful subtypes emerged from the analysis. They did not differ in demographic characteristics but did show, on average, distinct differences in behavioral and cognitive areas. Over half of the sample fell into a subtype described as typically autistic with abnormal verbal and nonverbal communication, aloofness, impaired social skills, and sensory disturbances. Another 19% were similarly autistic but with moderate to severe mental handicap. The remaining children formed two subtypes: a high-functioning Asperger-like group who were overactive and aggressive, and a small group who were impaired in social and language skills, had restricted interests, and a family history of learning problems. This study highlights important differences among children with autism and emphasizes relationships between cognitive functioning and subtypes of the disorder.

Screening for autism Agreement with diagnosis

Screening measures to identify very young children at risk for autism spectrum disorders include the Modified Checklist for Autism in Toddlers (M–CHAT) and the Social Communication Questionnaire (SCQ). To examine the validity of these written questionnaires, parents completed them prior to their childs diagnostic assessment at a tertiary autism clinic. The M–CHAT was given to 84 parents of 2 to 3-year-olds and the SCQ to 94 parents of 4 to 6-year olds. On both measures sensitivity was higher than specificity with positive predictive values 0.63–0.68. False negatives, or children with autism who were missed by screening, were somewhat higher functioning than true positives. Results were better for parents who spoke English as a second language, contrary to expectations. At this stage of development these tools would be recommended as part of more comprehensive surveillance programmes to identify children in need of further assessment but not to ‘screen out’ the possibility of autism.

Effect of secretin on children with autism: a randomized controlled trial

To determine the effect of intravenous porcine secretin on autistic behaviours in children aged 2 to 7 years, the effects of secretin on (1) performance on a standardized language measure, and (2) autistic behaviours, as rated by parents and child development professionals was examined. Employing a randomized, double‐blind, placebo‐controlled design, 95 participants were assigned to one of two groups and administered a single dose of either secretin or placebo. A follow‐up assessment was conducted 3 weeks after the injection. No significant differences in language or autistic behaviour measures were observed at the 3‐week follow‐up between the groups. Also, there was no significant difference in the proportion of individuals who improved by 6 points on the language measure at follow‐up. This study showed no significant effects of secretin on children with autism. Our results are consistent with a systematic review of randomized controlled trials evaluating the effect of secretin in children with autism.

Cerebrospinal fluid values for monoamine metabolites, γ-aminobutyric acid, and other amino compounds in Rett syndrome

We measured concentrations of 3-methoxy-4-hydroxy-phenylglycol, 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindoleacetic acid--the metabolites of noradrenaline, dopamine, and serotonin used as central neurotransmitters--in the cerebrospinal fluid (CSF) specimens of five girls with Rett syndrome. These patients met the clinical criteria for both inclusion and exclusion of the diagnosis of Rett syndrome. In contrast to previous reports, cerebral monoamine metabolites were present in normal concentrations in CSF. In addition, concentrations of gamma-aminobutyric acid and of a large number of other amino acids and related compounds were normal in the CSF of patients with the syndrome. We doubt that an underlying biochemical cause for this disorder has yet been discovered.

Blood serotonin concentrations and fenfluramine therapy in autistic children

Whole-blood serotonin concentrations of 31 autistic children, aged 2 1/2 to 16 years, 10 non-autistic retarded children, and 18 children with Down syndrome were measured by a fluorometric method and compared with those of normal children of similar age range. No significant difference in the serotonin concentration per milliliter of whole blood or per 1000 platelets was found between groups for autistic, retarded, or normal children, but the values for those with Down syndrome were significantly lower. A double-blind cross-over study on the effect of fenfluramine versus placebo in seven autistic boys over a period of 8 months demonstrated a significant decrease in blood serotonin levels during the fenfluramine phase in all subjects. Slight improvements were found in short-term auditory memory and some measures of receptive language skills, particularly in children functioning at a high level. There was no significant change in global psychometric measurements of general intelligence during therapy. No adverse clinical effect was observed other than weight loss of 6% in one child. We conclude that fenfluramine may have some selective favorable effects on increasing attention in high-functioning autistic children. Blood serotonin concentration may be followed as an indication of drug compliance during fenfluramine therapy, but does not appear to reflect clinical efficacy.

Rett syndrome: investigation of nine patients, including PET scan.

BACKGROUND We describe nine females with Rett Syndrome (RS), aged 14 to 26 years. All had had developmental delay before the end of their first year and had subsequently regressed to profound dementia with apraxia, ataxia, irregular respirations and often also seizures. METHODS The Revised Gesell developmental assessment and Alpern-Boll Developmental Profile were used in modified form. Volumetric measurements of basal ganglia using MRI were compared with the findings in nine age-matched volunteer females. Positron emission scans with [18F]-6-fluorodopa and [11C]-raclopride were performed under light anesthesia with intravenous Propofol, and the findings were compared with those in healthy control girls. Bidirectional sequencing of the coding regions of the MECP2 gene was investigated in blood samples for mutational analyses. RESULTS The RS females functioned at a mental age level ranging from about 4 to 15 months. The scores correlated with height, weight and head circumference. Magnetic resonance scans of basal ganglia showed a significant reduction in the size of the caudate heads and thalami in the Rett cases. Positron emission scans demonstrated that the mean uptake of fluorodopa in RS was reduced by 13.1% in caudate and by 12.5% in putamen as compared to the controls, while dopamine D2 receptor binding was increased significantly by 9.7% in caudate and 9.6% in putamen. Mutations in the coding regions of the MECP2 gene were present in all nine patients. No significant correlation between type and location of mutation and volumetric changes or isotope uptake was demonstrable. CONCLUSIONS Our findings suggest a mild presynaptic deficit of nigrostriatal activity in Rett syndrome.

Variability of Development in Three Siblings With Fragile X Syndrome

*Departments of Pediatrics and Psychology, University of British Columbia, Sunny Hill Hospital for Children, Vancouver, B.C. Correspondence to: Helena H. Ho, M.D., Child Development Diagnostic Program, Sunny Hill Hospital for Children, 3644 Slocan Street, Vancouver, B.C., V5M 3E8, office phone: (604) 434-4738. Twenty years after Martin and Bell’ published the first paper linking severe mental retardation in males with sexlinked inheritance, Dunn and Renpenning2 described a similar association in several Canadian families in British