CLARISSA BUENO
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/63, Hospital das Clínicas, Faculdade de Medicina
LIM/63, Hospital das Clínicas, Faculdade de Medicina
15 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 15
- BCKDK deficiency: a treatable neurodevelopmental disease amenable to newborn screening(2023) TANGERAAS, Trine; CONSTANTE, Juliana R.; BACKE, Paul Hoff; OYARZABAL, Alfonso; NEUGEBAUER, Julia; WEINHOLD, Natalie; BOEMER, Francois; DEBRAY, Francois G.; OZTURK-HISM, Burcu; EVREN, Gumus; TUBA, Eminoglu F.; UMMUHAN, Oncul; FOOTITT, Emma; DAVISON, James; MARTINEZ, Caroline; BUENO, Clarissa; MACHADO, Irene; RODRIGUEZ-POMBO, Pilar; AL-SANNAA, Nouriya; SANTOS, Mariela de los; LOPEZ, Jordi Muchart; OZTURKMEN-AKAY, Hatice; KARACA, Meryem; TEKIN, Mustafa; PAJARES, Sonia; ORMAZABAL, Aida; STOWAY, Stephanie D.; ARTUCH, Rafael; DIXON, Marjorie; MORKRID, Lars; GARCIA-CAZORLA, AngelesThere are few causes of treatable neurodevelopmental diseases described to date. Branched-chain ketoacid dehydrogenase kinase (BCKDK) deficiency causes branched-chain amino acid (BCAA) depletion and is linked to a neurodevelopmental disorder characterized by autism, intellectual disability and microcephaly. We report the largest cohort of patients studied, broadening the phenotypic and genotypic spectrum. Moreover, this is the first study to present newborn screening findings and mid-term clinical outcome. In this cross-sectional study, patients with a diagnosis of BCKDK deficiency were recruited via investigators' practices through a MetabERN initiative. Clinical, biochemical and genetic data were collected. Dried blood spot (DBS) newborn screening (NBS) amino acid profiles were retrieved from collaborating centres and compared to a healthy newborn reference population. Twenty-one patients with BCKDK mutations were included from 13 families. Patients were diagnosed between 8 months and 16 years (mean: 5.8 years, 43% female). At diagnosis, BCAA levels (leucine, valine and isoleucine) were below reference values in plasma and in CSF. All patients had global neurodevelopmental delay; 18/21 had gross motor function (GMF) impairment with GMF III or worse in 5/18, 16/16 intellectual disability, 17/17 language impairment, 12/17 autism spectrum disorder, 9/21 epilepsy, 12/15 clumsiness, 3/21 had sensorineural hearing loss and 4/20 feeding difficulties. No microcephaly was observed at birth, but 17/20 developed microcephaly during follow-up. Regression was reported in six patients. Movement disorder was observed in 3/21 patients: hyperkinetic movements (1), truncal ataxia (1) and dystonia (2). After treatment with a high-protein diet (>= 2 g/kg/day) and BCAA supplementation (100-250 mg/kg/day), plasma BCAA increased significantly (P < 0.001), motor functions and head circumference stabilized/improved in 13/13 and in 11/15 patients, respectively. Among cases with follow-up data, none of the three patients starting treatment before 2 years of age developed autism at follow-up. The patient with the earliest age of treatment initiation (8 months) showed normal development at 3 years of age. NBS in DBS identified BCAA levels significantly lower than those of the normal population. This work highlights the potential benefits of dietetic treatment, in particular early introduction of BCAA. Therefore, it is of utmost importance to increase awareness about this treatable disease and consider it as a candidate for early detection by NBS programmes. Tangeraas et al. describe the largest series of BCKDK deficiency patients to date, including responses to dietetic treatment. Early introduction of BCAA ameliorates the BCKDK deficiency phenotype. This treatable neurodevelopmental disease should be considered for inclusion in newborn screening programmes.
- Subacute Partially Reversible Leukoencephalopathy Expands the Aicardi-Goutieres Syndrome Phenotype(2023) BARCELOS, Isabella Peixoto de; BUENO, Clarissa; GODOY, Luis Filipe S.; PESSOA, Andre; COSTA, Larissa A.; MONTI, Fernanda C.; SOUZA-CABRAL, Katiane; LISTIK, Clarice; CASTRO, Diego; DELLA-RIPA, Bruno; FREUA, Fernando; PIRES, Lais C.; KRUGER, Lia T.; GHERPELLI, Jose Luiz D.; PIAZZON, Flavia B.; MONTEIRO, Fabiola P.; LUCATO, Leandro T.; KOK, FernandoObjective: To report a series of atypical presentations of Aicardi-Goutieres syndrome. Methods: Clinical, neuroimaging, and genetic data. Results: We report a series of six unrelated patients (five males) with a subacute loss of developmental milestones, pyramidal signs, and regression of communication abilities, with onset at ages ranging from 7 to 20 months, reaching a nadir after 4 to 24 weeks. A remarkable improvement of lost abilities occurred in the follow-up, and they remained with residual spasticity and dysarthria but preserved cognitive function. Immunization or febrile illness occurred before disease onset in all patients. CSF was normal in two patients, and in four, borderline or mild lymphocytosis was present. A brain CT scan disclosed a subtle basal ganglia calcification in one of six patients. Brain MRI showed asymmetric signal abnormalities of white matter with centrum semi-ovale involvement in five patients and a diffuse white matter abnormality with contrast enhancement in one. Four patients were diagnosed and treated for acute demyelinating encephalomyelitis (ADEM). Brain imaging was markedly improved with one year or more of follow-up (average of 7 years), but patients remained with residual spasticity and dysarthria without cognitive impairment. Demyelination relapse occurred in a single patient four years after the first event. Whole-exome sequencing (WES) was performed in all patients: four of them disclosed biallelic pathogenic variants in RNASEH2B (three homozygous p.Ala177Thr and one compound heterozygous p.Ala177Thr/p.Gln58*) and in two of them the same homozygous deleterious variants in RNASEH2A (p.Ala249Val). Conclusions: This report expands the phenotype of AGS to include subacute developmental regression with partial clinical and neuroimaging improvement. Those clinical features might be misdiagnosed as ADEM.
conferenceObject UPPER AIRWAY RESISTANCE SYNDROME IS ASSOCIATED WITH HIGH CYCLIC ALTERNATING PATTERN(2022) GODOY, L.; SOSTER, L.; BUENO, C.; TOGEIRO, S.; POYARES, D.; TUFIK, S.; PALOMBINI, L.- Haploidentical bone marrow transplantation with post transplant cyclophosphamide for patients with X-linked adrenoleukodystrophy: a suitable choice in an urgent situation(2018) FERNANDES, Juliana Folloni; BONFIM, Carmem; KERBAUY, Fabio Rodrigues; RODRIGUES, Morgani; ESTEVES, Iracema; SILVA, Nathalia Halley; AZAMBUJA, Alessandra Prandini; MANTOVANI, Luiz Fernando; KUTNER, Jose Mauro; LOTH, Gisele; KUWAHARA, Cilmara Cristina; BUENO, Clarissa; KONDO, Andrea Tiemi; RIBEIRO, Andreza Alice Feitosa; KOK, Fernando; HAMERSCHLAK, NelsonAllogeneic hematopoietic stem cell transplantation (HSCT) is the only treatment that enhances survival and stabilizes neurologic symptoms in X-linked adrenoleukodystrophy (X-ALD) with cerebral involvement, a severe demyelinating disease of childhood. Patients with X-ALD who lack a well-matched HLA donor need a rapid alternative. Haploidentical HSCT using post transplant cyclophosphamide (PT/Cy) has been performed in patients with malignant and nonmalignant diseases showing similar outcomes compared to other alternative sources. We describe the outcomes of transplants performed for nine X-ALD patients using haploidentical donors and PT/Cy. Patients received conditioning regimen with fludarabine 150 mg/m(2) , cyclophosphamide 29 mg/kg and 2 Gy total body irradiation (TBI) with or without antithymocyte globulin. Graft-vs.-host disease prophylaxis consisted of cyclophosphamide 50 mg/kg/day on days +3 and +4, tacrolimus or cyclosporine A and mycophenolate mofetil. One patient had a primary graft failure and was not eligible for a second transplant. Three patients had secondary graft failure and were successfully rescued with second haploidentical transplants. Trying to improve engraftment, conditioning regimen was changed, substituting 2 Gy TBI for 4 Gy total lymphoid irradiation. Eight patients are alive and engrafted (17-37 months after transplant). Haploidentical HSCT with PT/Cy is a feasible alternative for X-ALD patients lacking a suitable matched donor. Graft failure has to be addressed in further studies.
- Electrical status epilepticus during sleep in patients with congenital Zika virus syndrome: An unprecedented clinical finding(2020) KRUEGER, Mariana Braatz; MAGALHAES, Samir Camara; PESSOA, Andre; BUENO, Clarissa; MASRUHA, Marcelo Rodrigues; SOBREIRA-NETO, Manoel AlvesBackground: Brazil experienced a disproportionately higher rate of microcephaly cases in November 2015 with evidence of a causal link with Zika virus (ZIKV) infections during pregnancy. Epilepsy is a major neurological feature seen as part of congenital Zika virus syndrome (CZVS). Different seizure types and electroencephalo-graphic (EEG) abnormalities have been described in association with this syndrome. However, clinical and neurophysiological features of epilepsy seen in children with CZVS are not fully understood. Methods: We evaluated children with CZVS showing an EEG pattern of electrical status epilepticus during slow-wave sleep (ESES). Information on gender, age of onset of seizures, head circumference at birth, gross motor function at the time of diagnosis, of clinical and EEG aspects of seizures, EEG features and response to drug treatment was assessed. Results: Our case series included four patients. They were diagnosed with epilepsy between one month to 18 months of age and showed an ESES pattern at the age of three. They presented with a wide range of epileptic symptoms, but all experienced tonic seizures. Multiple drug treatment was the management approach for three patients; however, they showed poor response to treatment with conventional drugs used in the treatment of ESES. Conclusions: Children with CZVS may develop an EEG pattern of ESES. Clinicians and neurologists should be aware of this neurological presentation to improve the management of these patients.
- Editorial: Melatonin and biological rhythms: from bench to bedside(2023) BUENO, Clarissa; AMARAL, Fernanda Gaspar Do; SPRUYT, Karen
- Melatonin Therapy Improves Cardiac Autonomic Modulation in Pinealectomized Patients(2020) CAMPOS, Luciana Aparecida; BUENO, Clarissa; BARCELOS, Isabella P.; HALPERN, Bruno; BRITO, Leandro C.; AMARAL, Fernanda G.; BALTATU, Ovidiu Constantin; CIPOLLA-NETO, JoseThe purpose of this investigational study was to assess the effects of melatonin replacement therapy on cardiac autonomic modulation in pinealectomized patients. This was an open-label, single-arm, single-center, proof-of-concept study consisting of a screening period, a 3-month treatment period with melatonin (3 mg/day), and a 6-month washout period. The cardiac autonomic function was determined through heart rate variability (HRV) measures during polysomnography. Pinealectomized patients (n = 5) with confirmed absence of melatonin were included in this study. Melatonin treatment increased vagal-dominated HRV indices including root mean square of the successive R-R interval differences (RMSSD) (39.7 ms, 95% CI 2.0-77.4, p = 0.04), percentage of successive R-R intervals that differ by more than 50 ms (pNN50) (17.1%, 95% CI 9.1-25.1, p = 0.003), absolute power of the high-frequency band (HF power) (1,390 ms(2), 95% CI 511.9-2,267, p = 0.01), and sympathetic HRV indices like standard deviation of normal R-R wave interval (SDNN) (57.6 ms, 95% CI 15.2-100.0, p = 0.02), and absolute power of the low-frequency band (LF power) (4,592 ms(2), 95% CI 895.6-8,288, p = 0.03). These HRV indices returned to pretreatment values when melatonin treatment was discontinued. The HRV entropy-based regularity parameters were not altered in this study, suggesting that there were no significant alterations of the REM-NREM ratios between the time stages of the study. These data show that 3 months of melatonin treatment may induce an improvement in cardiac autonomic modulation in melatonin-non-proficient patients. ClinicalTrials.gov Identifier: NCT03885258.
- Cardiac autonomic control during non-REM and REM sleep stages in paediatric patients with Prader-Willi syndrome(2021) BRITO, Leandro C.; QUEIROGA, Thereza; FRANCO, Ruth R.; PASSONE, Caroline G. B.; LOPES, Maria-Cecilia; SHEA, Steven A.; BUENO, Clarissa; SOSTER, Leticia M. S. F. A.Cardiac death is the second most prevalent cause in Prader-Willi syndrome (PWS). Paediatric patients with PWS often present cardiac autonomic dysfunction during wakefulness, obesity and sleep-disordered breathing. However, the extent of cardiac autonomic modulation during sleep in PWS has not been documented. The objective of this study was to assess alterations in cardiac autonomic modulation of paediatric patients with PWS during different sleep stages. Thirty-nine participants in three groups: 14 PWS, 13 sex and age-matched lean controls (LG) and 12 obese-matched controls (OB). All participants underwent overnight polysomnography, including continuous electrocardiogram recordings. Heart rate variability (HRV) was analysed during representative periods of each sleep stage through time and frequency domains calculated across 5-min periods. Between-within ANOVAs were employed (p < .05). The results show that total HRV was lower in PWS than OB and LG during slow-wave sleep (SWS) (standard deviation of all NN intervals [SDNN] ms,p = .006). Parasympathetic modulation assessed by time-domain analysis was lower during SWS in PWS compared to both OB and LG (square root of the mean of the sum of the squares of differences between adjacent NN intervals [RMSSD] ms,p = .004; SDSD, standard deviation of differences between adjacent NN intervals [SDSD] ms,p = .02; number of adjacent NN intervals differing by >50 ms [NN50] ms,p = .03; proportion of adjacent NN intervals differing by >50 ms [pNN50] ms,p = .01). Sympathovagal balance assessed by frequency-domain analysis was lower during both N2 and SWS than during the rapid eye movement (REM) sleep stage, but not different among groups. In conclusion, this group of paediatric patients with PWS had impaired cardiac autonomic balance due to reduced parasympathetic modulation during SWS. This result could imply an underlying increased cardiovascular risk in PWS even during early age and independent of obesity.
- A questionnaire study on sleep disturbances associated with Prader-Willi syndrome(2020) QUEIROGA, Thereza Lemos de Oliveira; DAMIANI, Durval; LOPES, Maria Cecilia; FRANCO, Ruth; BUENO, Clarissa; SOSTER, LeticiaBackground: This study aimed to investigate the presence of sleep disturbances in children with Prader-Willi syndrome (PWS) using the Sleep Disturbance Scale for Children (SDSC). Methods: The SDSC, which was designed to identify the presence and severity of different sleep disorders, was applied to 50 patients with PWS and 112 controls. Results: Patients with PWS achieved worse scores in the sleep-disordered breathing and disorders in initiating and maintaining sleep in the SDSC questionnaire as compared with controls. We also observed that patients with PWS were more prone to having hyperhidrosis. We did not observe significant differences in the presence of other types of sleep disorders (such as hypersomnolence) between the PWS and control groups. Conclusions: The results obtained with the SDSC questionnaire showed that children with PWS have more sleep breathing disorders and disorders in initiating and maintaining sleep as compared to controls. Additionally, we demonstrated that patients with PWS associates significantly with the presence of hyperhidrosis during sleep. However, SDSC was not reliable to identify the excessive daytime somnolence in patients with PWS, as previously reported in the literature.
- Arginase 1 deficiency presenting as complicated hereditary spastic paraplegia(2022) FREUA, Fernando; ALMEIDA, Mariana Espindola de Castro; NOBREGA, Paulo Ribeiro; PAIVA, Anderson Rodrigues Brandao de; DELLA-RIPA, Bruno; CUNHA, Paulina; MACEDO-SOUZA, Lucia Ines; BUENO, Clarissa; LYNCH, David S. S.; HOULDEN, Henry; LUCATO, Leandro Tavares; KOK, FernandoArgininemia or arginase deficiency is a metabolic disorder caused by pathogenic variants in ARG1 and consists of a variable association of progressive spastic paraplegia, intellectual disability, and seizures. Hereditary spastic paraplegia (HSP) is a group of inherited diseases whose main feature is a progressive gait disorder characterized by lower limb spasticity. This study presents seven patients with arginase 1 deficiency from six different families, all with an initial diagnosis of complicated HSP. We evaluated the clinical data of seven patients belonging to six independent families who were diagnosed with hyperargininemia in a neurogenetics outpatient clinic. All patients had lower limb spasticity and six had global developmental delay. Five individuals had intellectual disability and two had epilepsy. Psychiatric abnormalities were seen in two patients. In two participants of this study, magnetic resonance imaging (MRI) disclosed thinning of the corpus callosum. Molecular diagnosis was made by whole-exome sequencing. All variants were present in homozygosis; we identified two novel missense variants, one novel frameshift variant, and one previously published missense variant. A clinical diagnosis of early-onset complicated hereditary spastic paraplegia was made in all patients. Two patients were initially suspected of having SPG11 because of thinning of the corpus callosum. As argininemia may present with a highly penetrant phenotype of spastic paraplegia associated with additional symptoms, this disease may represent a specific entity among the complicated HSPs.