Metformin in an Adolescent with Significant Weight Gain.

Address correspondence to: Barbara J. Coffey, MD, MS, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1230, New York, New York 10029, E-mail: Barbara.coffey@mssm.eduChief ComplaintA.was a 13-year-old boy who had been diagnosed with autistic spectrum disorder (ASD); anxiety disorder, not otherwise specified; oppositional defiant disorder (ODD); and attention-deficit/hyperactivity disorder (ADHD) referred for worsening irritability and aggression.History of Present IllnessA. was first diagnosed with ADHD and anxiety disorder in preschool. Parents reported that since age four years, he was always "on the go" and had difficulty sitting still, talked excessively, interrupted others, and had difficulties waiting his turn. They reported that he fidgeted and squirmed a lot. He was initially treated for these symptoms with play therapy. At age seven years A. started treatment with a long-acting mixed amphetamine salt, which was effective for four years. Parents report that the amphetamine was discontinued because A. described seeing his deceased grandfather and an American revolutionary figure talking to him. He was subsequently started on guanfacine, which was effective for both hyperactivity and inattention symptoms.In addition, parents report that A. had developed repetitive stereotyped movements and mannerisms, such as twaddling his fingers and flapping his hands, as a toddler. He had a range of restricted interests such as Greek and Egyptian mythology and Legos. He had difficulties maintaining eye contact and sustaining conversation. He had difficulty with social and emotional reciprocity, and did not understand social cues. He was unable to form or sustain relationships, particularly with peers. Parents report that he tended to focus on one peer each school year that he would describe as his enemy. Over the years, although he invited peers to his birthday parties, he was never invited to others' parties. He was reported to continue to talk about topics even when others had lost interest. He imitated phrases and tones from characters in some TV shows. He was reported to have had a rigid morning routine that involved getting dressed in a certain order.A. was referred for neuropsychological screening at age eight years and reported to have an "average IQ" in the context of a diagnosis of ASD. At age 11 years, A. was evaluated at a Regional Autism Center and the ASD diagnosis was confirmed. Evaluation at that time included metabolic screening and chromosomal and DNA studies. Polymerase chain reaction evaluation showed one fragile X mental retardation 1 (FMR1) allele with only 30 CGG repeats in the FMR1 locus (a negative finding, given the normal range of 5-44). However, a point mutation or gene rearrangement causing fragile X syndrome could not be ruled out. A.'s complete blood count, comprehensive metabolic panel, and fasting lipid profile were all essentially within normal limits, except for slightly low high density lipoprotein of 39 (normal range, 40-60). An Individualized Educational Plan (IEP) was recommended for school.Despite medical and educational intervention, parents reported that A. continued to experience irritability and aggression, which became significantly worse six months prior to referral. A.'s irritability reportedly resulted from being redirected from restricted interests and activities. In school, he refused to follow rules and argued with adults. Parents reported that A.'s oppositional behaviors disrupted his learning, and as a result, his grades declined. A.'s irritability was reported to intensify in school, despite support from a classroom aide. A. was subsequently referred for behavioral therapy, including applied behavior analysis (ABA), and family therapy. He participated in family therapy for two years, but the family did not follow through on the ABA referral. They also underwent a two-week intensive family intervention program at the regional center. …