RESUMO
Fanconi-Bickel syndrome (FBS) is a rare metabolic disorder caused by decreased glucose transporter 2 (GLUT2) function due to several known mutations in the SLC2A2 gene. As of 2020, 144 cases of FBS have been described in the literature. Metabolic and somatic sequelae include dysglycemia and accumulation of glycogen in the kidney and liver. However, there are no descriptions in the literature of possible neuropsychiatric manifestations of FBS. This case report is to our knowledge the first in this regard, describing a patient with FBS who was admitted to our psychiatric inpatient unit while experiencing acute mania. We conceptualize the case as a novel psychiatric presentation of acute mania in FBS, which may inform our understanding of bipolar disorder pathophysiology because of the hypothesized functional changes in neural pathways involving the paraventricular thalamus induced by decreased GLUT2 activity in FBS.
Assuntos
Transtorno da Compulsão Alimentar , Transtorno Bipolar , Estimulantes do Sistema Nervoso Central , Humanos , Dimesilato de Lisdexanfetamina/efeitos adversos , Transtorno da Compulsão Alimentar/complicações , Transtorno da Compulsão Alimentar/diagnóstico , Transtorno da Compulsão Alimentar/tratamento farmacológico , Transtorno Bipolar/complicações , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/efeitos adversos , Resultado do TratamentoRESUMO
A potential link between switching to aripiprazole and worsening of psychosis was first reported in the early 2000s. There have since been numerous published case reports describing this phenomenon, but only recently has the concept of a theoretical aripiprazole-induced dopamine supersensitivity psychosis (DSP) caused by D2 receptor activation in patients undergoing a switch to aripiprazole appeared in the literature. There is less awareness in clinical practice of the possibility of inducing DSP with aripiprazole, which may be particularly severe in some patients. The objective of this article is to present four cases demonstrating rapid and dramatic onset of DSP during switching to aripiprazole. In each case, a patient with a Diagnostic and statistical manual of mental disorders (5th ed.) diagnosis of schizophrenia experienced severe worsening of psychosis within 4-5 days of abrupt switching to aripiprazole from a full D2 antagonist. To our knowledge, this is the first case series characterizing the previously well-documented worsening of psychosis during switching to aripiprazole specifically as aripiprazole-induced DSP. We discuss clinical relevance, prevention and future directions. Careful cross-titration per clinical practice guidelines may reduce occurrence of DSP during aripiprazole switching or augmentation treatment.
Assuntos
Antipsicóticos , Transtornos Psicóticos , Esquizofrenia , Antipsicóticos/efeitos adversos , Aripiprazol/efeitos adversos , Dopamina/fisiologia , Humanos , Transtornos Psicóticos/tratamento farmacológico , Esquizofrenia/tratamento farmacológicoRESUMO
Ubxd8, a multidomain protein sensor for long-chain unsaturated fatty acids (FAs), plays a crucial role to maintain cellular homeostasis of FAs. Ubxd8 polymerizes upon interaction with long-chain unsaturated FAs, but the molecular mechanism involved in this polymerization remains unclear. Here we report that the UAS domain of Ubxd8 mediates this polymerization. We show that a positively charged surface area in the domain is required for the reaction. Mutations changing the positively charged residues in this area to glutamates prevented long-chain unsaturated FAs from inducing oligomerization of Ubxd8. Consequently, the mutant protein no longer responded to regulation by long-chain unsaturated FAs in cultured cells. Long-chain unsaturated FAs also induced polymerization of Fas-associated factor 1 (FAF1), the only other mammalian protein that contains a UAS domain homologous to that of Ubxd8. These results provide further insights into protein-FA interactions by identifying the UAS domain as a motif interacting with long-chain unsaturated FAs.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/química , Proteínas Sanguíneas/química , Ácidos Graxos Insaturados/química , Proteínas de Membrana/química , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Proteínas Reguladoras de Apoptose , Proteínas Sanguíneas/metabolismo , Células CHO , Células Cultivadas , Cricetulus , Ácidos Graxos Insaturados/metabolismo , Humanos , Proteínas de Membrana/metabolismo , Modelos Moleculares , Polimerização , Estrutura Terciária de ProteínaRESUMO
An elderly patient with no abnormal bleeding presented with prolongation of the activated partial thromboplastin time (aPTT). Preincubation of plasma with aPTT reagent caused shortening of the abnormal clotting time. Plasma prekallikrein (PK) activity and antigen were <5 u/dL. Molecular analysis showed a homozygous Arg94Stop substitution in the PK gene, predicted to prevent expression of the mutant allele. The five heterozygous offspring of the proband each showed a normal aPTT but reduced PK activity and antigen. This is the first description of a kindred in which absence of expression of one or both PK alleles has been confirmed by genotype.