Depression and cognitive deficits in AIDS patients : preliminary findings - Hospital de Clínicas de Porto Alegre (HCPA)

Os autores a partir de revisão bibliográfica e experiência clínica evidenciam alta prevalência de transtornos depressivos e déficit cognitivo (OC) em pacientes com AIDS, e a partir disto elaboram protocolo de pesquisa para avaliar estes transtornos em pacientes aidéticos internados no Hospital de Clínicas de Porto Alegre (HCPA), com o uso de instrumentos objetivos de medida de depressão e DC. São aplicados o MiniExame do Estado Psiquiátrico (MMSE - Mini-MentaiState- Examination) de Folstein e o Inventário de Beck para Depressão (Beck Depression lnventory - BOI) para medida de DC e Depressão, respectivamente em uma amostra de 30 pacientes. Foi encontrada prevalência de 27,6% de DC e 60% de depressão (incluindo intensidades leves, moderada e severa). Os subitens mais afetados são, para DC, os de cálculo numérico, construção gráfica e escrita, e obediência a registros gráficos; e para depressão, queixas de insatisfação, inibição no trabalho, irritabilidade, fadiga, isolamento e indecisão, diminuição do sono e pessimismo. Os itens globais dão uma dimensão considerável de problemas depressivos e cognitivos em {.:acientes aidéticos hospitalizados, com subescores apontando para especificidades nas áreas cognitivas, envolvendo os aspectos mais complexos de desempenho como expressão e construção verbal e gráfica (redacão de frase, construção de pentágonos em interseccÍio) cálculo numérico (subtração seriada de sete em ~eteJ e execução de comando verbal.The authors describe the preliminary findings of a clinicai research designed to measure the prevalence of depression and cognitive deficits in AIDS patients hospitalized at the Hospital de Clínicas de Porto Alegre (HCPA), utilizing the Beck Depression lnventory (BOI) and the Mini-Mental State Examination (MMSE). The prevalence was 21.6% for cognit ive deficits and 60% for depression. The items that were answered most frequently wrong among those with cognitive deficit were those for numeric calculation, written and graphic construction and graphic analysis and interpretation. The depressives failed to answer correctly mostly the items for insatisfaction, irritability, work inhibition, fatigue, withdrawal, indecisiveness, sleep and pessimism. These findings provide preliminary estlmates for those psychiatric syndromes (cognitive deficit and depression) and suggest that the symptom profile of these states may display specific deficits and problems, and require further studies with larger samples to confirm that prevalence and specificity

Biallelic variants in HPDL cause pure and complicated hereditary spastic paraplegia.

Human 4-hydroxyphenylpyruvate dioxygenase-like (HPDL) is a putative iron-containing non-heme oxygenase of unknown specificity and biological significance. We report 25 families containing 34 individuals with neurological disease associated with biallelic HPDL variants. Phenotypes ranged from juvenile-onset pure hereditary spastic paraplegia to infantile-onset spasticity and global developmental delays, sometimes complicated by episodes of neurological and respiratory decompensation. Variants included bona fide pathogenic truncating changes, although most were missense substitutions. Functionality of variants could not be determined directly as the enzymatic specificity of HPDL is unknown; however, when HPDL missense substitutions were introduced into 4-hydroxyphenylpyruvate dioxygenase (HPPD, an HPDL orthologue), they impaired the ability of HPPD to convert 4-hydroxyphenylpyruvate into homogentisate. Moreover, three additional sets of experiments provided evidence for a role of HPDL in the nervous system and further supported its link to neurological disease: (i) HPDL was expressed in the nervous system and expression increased during neural differentiation; (ii) knockdown of zebrafish hpdl led to abnormal motor behaviour, replicating aspects of the human disease; and (iii) HPDL localized to mitochondria, consistent with mitochondrial disease that is often associated with neurological manifestations. Our findings suggest that biallelic HPDL variants cause a syndrome varying from juvenile-onset pure hereditary spastic paraplegia to infantile-onset spastic tetraplegia associated with global developmental delays

Biallelic variants in HPDL cause pure and complicated hereditary spastic paraplegia

Human 4-hydroxyphenylpyruvate dioxygenase-like (HPDL) is a putative iron-containing non-heme oxygenase of unknown specificity and biological significance. We report 25 families containing 34 individuals with neurological disease associated with biallelic HPDL variants. Phenotypes ranged from juvenile-onset pure hereditary spastic paraplegia to infantile-onset spasticity and global developmental delays, sometimes complicated by episodes of neurological and respiratory decompensation. Variants included bona fide pathogenic truncating changes, although most were missense substitutions. Functionality of variants could not be determined directly as the enzymatic specificity of HPDL is unknown; however, when HPDL missense substitutions were introduced into 4-hydroxyphenylpyruvate dioxygenase (HPPD, an HPDL orthologue), they impaired the ability of HPPD to convert 4-hydroxyphenylpyruvate into homogentisate. Moreover, three additional sets of experiments provided evidence for a role of HPDL in the nervous system and further supported its link to neurological disease: (i) HPDL was expressed in the nervous system and expression increased during neural differentiation; (ii) knockdown of zebrafish hpdl led to abnormal motor behaviour, replicating aspects of the human disease; and (iii) HPDL localized to mitochondria, consistent with mitochondrial disease that is often associated with neurological manifestations. Our findings suggest that biallelic HPDL variants cause a syndrome varying from juvenile-onset pure hereditary spastic paraplegia to infantile-onset spastic tetraplegia associated with global developmental delays