Valproate-induced hyperammonemic encephalopathy (VHE) is a rare and severe side effect that can occur with valproic acid (VPA) therapy, despite therapeutic doses and normal serum levels of valproate. The typical signs of this condition include a sudden onset of impaired consciousness, focal neurologic symptoms, and an increase in seizure frequency. The exact cause of VHE is unknown, but it is believed to be related to the accumulation of toxic VPA metabolites and increased levels of ammonia that can cause swelling of the astrocytes and cerebral edema. We present a case of a 19-year-old male patient with a history of bipolar disorder on valproic acid 250 mg daily, admitted to the hospital after a new-onset seizure. He was found to have elevated levels of ammonia in his blood, despite having therapeutic levels of valproate and no liver dysfunction. His symptoms improved with discontinuation of the medication and his ammonia levels decreased. We discuss possible mechanisms and risk factors leading to encephalopathy while on valproate therapy. VHE should be considered a possibility when patients treated with valproate show signs of impaired consciousness.

Gastrointestinal (GI) problems are common in Phelan-McDermid syndrome (PMS). Chewing and swallowing difficulties, dental problems, reflux disease, cyclic vomiting, constipation, incontinence, diarrhoea, and nutritional deficiencies have been most frequently reported. Therefore, this review summarises current findings on GI problems and addresses the fundamental questions, which were based on parental surveys, of how frequent GI problems occur in PMS, what GI problems occur, what consequences (e.g., nutritional deficiencies) GI problems cause for individuals with PMS, and how GI problems can be treated in individuals with PMS. Our findings show that gastrointestinal problems have a detrimental effect on the health of people with PMS and are a significant burden for their families. Therefore, we advise evaluation for these problems and formulate care recommendations.

The 22q13.3 deletion, or Phelan-McDermid syndrome, is characterized by global intellectual disability, generalized hypotonia, severely delayed or absent speech associated with features of autism spectrum disorder, and minor dysmorphisms. Its behavioral phenotype comprises sleep disturbances, communication deficits, and motor perseverations. Data on psychological dysfunctions are so far not available. Previous studies have suggested that the loss of one copy of the gene SH3 and multiple ankyrin repeat domains 3 (SHANK3) is related to the neurobehavioral phenotype. Additional genes proximal to SHANK3 are also likely to play a role in the phenotype of patients with larger deletions. The present paper describes two adult brothers with an identical 2.15 Mb 22qter (22q13.32q13.33) deletion, of whom the youngest was referred for evaluation of recurrent mood changes. In both patients, magnetic resonance imaging of the brain showed hypoplasia of the vermis cerebelli. Extensive clinical examinations led to a final diagnosis of atypical bipolar disorder, of which symptoms fully remitted during treatment with a mood stabilizer. In the older brother, a similar psychopathological picture appeared to be present, although less severe and with a later onset. It is concluded that the behavioral phenotype of the 22q13.3 deletion syndrome comprises absent or delayed speech and perseverations with associated autistic-like features, whereas its psychopathological phenotype comprises an atypical bipolar disorder. The latter may have implications for the treatment regime of the syndrome-related behavioral disturbances.