Cognitive and behavioral phenotype of children with pseudohypoparathyroidism type 1A.

Pseudohypoparathyroidism 1A (PHP1A) is a rare, genetic disorder. Most patients with PHP1A have cognitive impairment but this has not been systematically studied. We hypothesized that children with PHP1A would have lower intelligent quotient (IQ) scores than controls. To evaluate cognition and behavior, we prospectively enrolled children with PHP1A, one unaffected sibling (when available) and controls matched on BMI/age/gender/race. Evaluations included cognitive and executive function testing. Parents completed questionnaires on behavior and executive function. We enrolled 16 patients with PHP1A, 8 unaffected siblings, and 15 controls. Results are presented as mean (SD). The PHP1A group had a composite IQ of 85.9 (17.2); 25% had a composite IQ < -2 SD. The PHP1A group had significantly lower IQs than matched controls (composite IQ -17.3, 95%CI -28.1 to -6.5, p < 0.01) and unaffected siblings (composite IQ -21.5, 95%CI -33.9 to -9.1, p < 0.01). Special education services were utilized for 93% of the patients with PHP1A. Deficits were observed in executive function and parents reported delayed adaptive behavior skills and increased rates of attention deficit hyperactivity disorder. In conclusion, children with PHP1A have lower intelligence quotient scores, poorer executive function, delayed adaptive behavior skills, and increased behavior problems.

Gastrointestinal dysfunction in autism: parental report, clinical evaluation, and associated factors.

The objectives of this study were to characterize gastrointestinal dysfunction (GID) in autism spectrum disorder (ASD), to examine parental reports of GID relative to evaluations by pediatric gastroenterologists, and to explore factors associated with GID in ASD. One hundred twenty-one children were recruited into three groups: co-occurring ASD and GID, ASD without GID, and GID without ASD. A pediatric gastroenterologist evaluated both GID groups. Parents in all three groups completed questionnaires about their child's behavior and GI symptoms, and a dietary journal. Functional constipation was the most common type of GID in children with ASD (85.0%). Parental report of any GID was highly concordant with a clinical diagnosis of any GID (92.1%). Presence of GID in children with ASD was not associated with distinct dietary habits or medication status. Odds of constipation were associated with younger age, increased social impairment, and lack of expressive language (adjusted odds ratio in nonverbal children: 11.98, 95% confidence interval 2.54-56.57). This study validates parental concerns for GID in children with ASD, as parents were sensitive to the existence, although not necessarily the nature, of GID. The strong association between constipation and language impairment highlights the need for vigilance by health-care providers to detect and treat GID in children with ASD. Medications and diet, commonly thought to contribute to GID in ASD, were not associated with GID status. These findings are consistent with a hypothesis that GID in ASD represents pleiotropic expression of genetic risk factors.