Cheema, Anvir

Introduction: Alexander disease is a rare neurodegenerative disease caused by variants in the glial fibrillary acidic protein gene (GFAP). This disorder can develop as an infantile, juvenile or adult-onset form and is characterized by several clinical features, including macrocephaly, seizures, ataxia, and bulbar/pseudobulbar signs. While the majority of these patients have the more progressive infantile form which causes severe leukodystrophy and early death; the less common adult form is more variable (ie, onset age, symptoms), with bulbar dysfunction as the primary feature. Case Report: In our investigation, we describe a patient with progressive neuromuscular issues including dyspnea, dysphagia, dysarthria and progressive ataxia with palatal tremor. Conclusions: Through genetic testing, we determined that our patient has a novel variant in GFAP typical of Alexander disease.

Cardiotoxicity has been extensively reported in venlafaxine (VEN) overdoses. Asthenia is also among the common side effects described for this antidepressant. VEN is metabolized mainly by CYP2D6 and to a minor extent by CYP2C19 to the major active metabolite O-desmethylvenlafaxine (ODV). Altered pharmacokinetic parameters in patients with polymorphisms in the CYP2D6 and CYP2C19 genes that result in decreased enzymatic activity have been documented. Here we describe a patient case of VEN associated palpitations and asthenia. The patient takes VEN extended release 150 mg twice daily. Genotyping confirmed the patient is a poor metabolizer for CYP2D6 and an intermediate metabolizer for CYP2C19. We propose that the palpitations and asthenia are related to sustained VEN exposure due to reduced metabolism.