DEBORA ROMEO BERTOLA
Projetos de Pesquisa
Unidades Organizacionais
Instituto da Criança, Hospital das Clínicas, Faculdade de Medicina - Médico
BIO, IB
LIM/36 - Laboratório de Pediatria Clínica, Hospital das Clínicas, Faculdade de Medicina
BIO, IB
LIM/36 - Laboratório de Pediatria Clínica, Hospital das Clínicas, Faculdade de Medicina
17 resultados
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- Mucopolysaccharidosis Type IVA: Evidence of Primary and Secondary Central Nervous System Involvement(2014) BORLOT, Felippe; ARANTES, Paula Ricci; QUAIO, Caio Robledo; FRANCO, Jose Francisco da Silva; LOURENCO, Charles Marques; GOMY, Israel; BERTOLA, Debora Romeo; KIM, Chong AeMucopolysaccharidosis type IVA is a rare lysosomal storage disease caused by a deficiency of N-acetylgalactosamine 6-sulfatase. Studies usually focus on skeletal abnormalities and their consequences. This study explores the neurological manifestations in a cohort of mucopolysaccharidosis type IVA patients, with a detailed focus on brain and spinal magnetic resonance imaging (MRI) findings. We performed a cross-sectional study involving nine patients with a biochemical confirmation of mucopolysaccharidosis type IVA. The protocol consists of a comprehensive clinical examination and brain and spinal cord MRI analysis for all subjects. The mean age was 16.4 years (+/- 5.7) and the mean onset of symptoms was 11.5 months (+/- 6.3). Overall, cognition was spared in all but one patient and motor weakness was a constant finding in all patients. Deep sensation impairment was found in six patients. The brain MRIs showed non-specific white matter changes in two patients. Other abnormalities such as clival hypoplasia, basilar invagination, and arachnoid cists appeared in seven of the nine patients. Eight patients presented spinal cord compression, and in three of them, two spinal levels were compromised. Odontoid hypoplasia and degenerative features in the neuroaxis were present in all patients. Our experience with mucopolysaccharidosis type IVA patients supports the evidence of central nervous system involvement. We emphasize the importance of regular clinical assessments with complete MRI studies, as an attempt to detect the early signs of spinal cord compression. This evaluation may be especially important before surgical interventions, as occult lesions may become symptomatic and promote postoperative unfavorable outcomes. (c) 2014 Wiley Periodicals, Inc.
- Impact of ERT and follow-up of 17 patients from the same family with a mild form of MPS II(2022) STEPHAN, Bruno de Oliveira; QUAIO, Caio Robledo; SPOLADOR, Gustavo Marquezani; PAULA, Ana Carolina de; CURIATI, Marco Antonio; MARTINS, Ana Maria; LEAL, Gabriela Nunes; TENORIO, Artur; FINZI, Simone; CHIMELO, Flavia Teixeira; MATAS, Carla Gentile; HONJO, Rachel Sayuri; BERTOLA, Debora Romeo; KIM, Chong AeBackground: Mucopolysaccharidosis type II, also known as Hunter syndrome, is a rare X-linked recessive disorder caused by deficiency of the lysosomal enzyme Iduronate-2-Sulfatase (IDS), leading to progressive accumulation of Glycosaminoglycans (GAGs) in several organs. Over the years, Enzyme Replacement Therapy (ERT) has provided significant benefits for patients, retarding the natural progression of the disease. Results: The authors evaluated 17 patients from the same family with a mild form of MPS type II; the proband had developed acute decompensated heart failure refractory to clinical measurements at 23 years and needed a rather urgent heart transplant; however, he died from surgical complications shortly after the procedure. Nevertheless, subsequent to his tragic death, 16 affected male relatives were detected after biochemical tests identifying the low or absent activity of the IDS enzyme and confirmed by molecular analysis of the IDS gene. Following diagnosis, different options of treatment were chosen: 6 patients started ERT with Elaprase (R) (Idursulfase) soon after, while the other 10 remained without ERT. Eventually, 4 patients in the latter group began ERT with Hunterase (R) (Idursulfase Beta). None presented adverse effects to either form of the enzyme. Among the 6 individuals without any ERT, two died of natural causes, after reaching 70 years. Despite the variable phenotype within the same family (mainly heart dysfunctions and carpal tunnel syndrome), all 14 remaining patients were alive with an independent lifestyle. Conclusion: Here, the authors report the variable progress of the disease with and without ERT in a large Brazilian family with a slowly progressive form of MPS II, harboring the same missense variant in the IDS gene.
- New insights in mucopolysaccharidosis type VI: Neurological perspective(2014) BORLOT, Felippe; ARANTES, Paula Ricci; QUAIO, Caio Robledo; FRANCO, Jose Francisco da Silva; LOURENCO, Charles Marques; BERTOLA, Debora Romeo; KIM, Chong AeObjective: Mucopolysaccharidosis type VI is a rare autosomal recessive storage disorder, caused by deficiency of arylsulfatase B. Data on neurological involvement in mucopolysaccharidosis type VI patients under enzyme-replacement therapy are limited. This study explores the neurological and magnetic resonance imaging findings in a sample of mucopolysaccharidosis type VI patients receiving enzyme-replacement therapy. Methods: We performed a cross-sectional study including six patients with biochemical confirmation of mucopolysaccharidosis type VI and at least 105 consecutive weeks (two years) receiving intravenous enzyme-replacement therapy. The protocol included a comprehensive clinical examination, brain and spinal cord magnetic resonance imaging for all subjects. Results: Overall, cognition was spared, while we found presence of hearing impairment, increasing in deep tendon reflexes and deep sensation reduction in three patients. In addition to the classical abnormalities related to other types of mucopolysaccharidosis, imaging studies demonstrated morphological changes in anatomy of middle cranial fossa and sella shape. Even in asymptomatic or mild compromised patients, spinal cord compression was found. In four patients we noticed atlantoaxial joint subluxation and three had cervical spinal stenosis. Degenerative processes involving vertebral column, including discal protrusion and axis abnormalities, were present in all patients. Conclusions: Neuroaxis involvement was a universal finding and neurological examination might not predict the severity of the disease in course. Image studies should not be performed according exclusively clinical parameters for these patients, once we have demonstrated that neurological involvement may be silent in these patients.
- Report of a Large Brazilian Family With a Very Attenuated Form of Hunter Syndrome (MPS II)(2012) QUAIO, C. R. D. C.; GRINBERG, H.; VIEIRA, M. L. C.; PAULA, A. C.; LEAL, G. N.; GOMY, I.; LEISTNER-SEGAL, S.; GIUGLIANI, R.; BERTOLA, D. R.; KIM, C. A.Hunter syndrome, or Mucopolysaccharidosis type II (MPS II), is a rare X-linked recessive disorder caused by a deficiency of the lysosomal enzyme iduronate-2-sulfatase (IDS). The phenotypic spectrum varies from severe to attenuated clinical forms. We report a large Brazilian family with 16 affected individuals exhibiting a very attenuated form of MPS II. Fourteen female carriers were also identified. Twelve affected male patients, whose ages ranged from 1 to 35 years, were examined. Molecular analysis showed a novel missense mutation (p.A77D) in the IDS gene, confirming the diagnosis. Nine of the family members presented some degree of heart damage, though only the proband became symptomatic and required heart transplantation. One 19-year-old adult and 1-year-old twin boys each had a normal echocardiogram. Short stature was found in two adults while macrocephaly was found in one; the remaining adults had anthropometric measures within normal range. All affected adults had normal cognitive development and were able to perform normal daily activities, except one who had mild learning disability. Two patients died due to natural causes beyond 70 years of age. The female carriers did not present any signs of disease. In this large family with a mild form of MPS II and variable degree of clinical manifestations, it is noteworthy that several affected individuals have remained asymptomatic even at advanced age and even without enzyme replacement therapy.
- A Possible Role of Different PTPN Genes in Immune Regulation(2012) QUAIO, C. R. D. C.; DUTRA, R. L.; BRASIL, A. S.; PEREIRA, A. C.; KIM, C. A.; BERTOLA, D. R.
- Vertebral segmentation defects in a Brazilian cohort: Clinical and molecular analysis focused on spondylocostal dysostosis(2022) LINNENKAMP, Bianca; GIRARDI, Raissa; ROCHA, Leticia; YAMAMOTO, Guilherme; CERONI, Jose Ricardo; MENDES, Antonia Elisabeth Cristhina; HONJO, Rachel; OLIVEIRA, Luiz Antonio; AMEMIYA, Raphael Bruno; QUAIO, Caio; OLIVEIRA FILHO, Joao Bosco de; KIM, Chong Ae; BERTOLA, Debora
- Multicentric study on the diagnosis of Fabry's disease using angiokeratoma biopsy registries(2015) KELMANN, Samantha Vernaschi; QUAIO, Caio Robledo D'Angioli Costa; HONJO, Rachel Sayuri; BERTOLA, Debora Romeo; ROSA NETO, Nilton Salles; LOURENCO, Charles Marques; D'ALMEIDA, Vania; LELLIS, Rute Facchini; RIVITTI-MACHADO, Maria Cecilia; ENOKIHARA, Milvia Maria Simoes e Silva; MICHALANY, Nilceo S.; KIM, Chong Ae
conferenceObject NATURAL KILLER CELL DEFICIENCY IN PATIENTS WITH MUCOPOLYSACCHARIDOSES(2012) TORRES, L. C.; QUAIO, C. R. D. C.; FRANCO, J. F.; GOMY, I.; BERTOLA, D. R.; KULIKOWSKI, L. D.; SAMPAIO, M. Carneiro; KIM, C. A.Mucopolysaccharidoses (MPSs) are a group of inherited metabolic disorders characterized by the deficient activity of catabolic enzymes in the lysosomes and its consequent abnormal accumulation of deposits of glycosaminoglycans. The lysosomal dysfuction caused by this irregular storage is responsible for the clinical manifestations seen in MPS. Once the lysosome is also important for normal functioning of the immune system, playing a key role in the expression of cellular membrane receptors, the presentation of antigens, the secretion of cytokines and phagocytosis, we presume that these processes may be impaired in patients with MPS. The presence of recurrent respiratory infections in these individuals may be a clinical clue of the immune dysregulation in MPSs. Natural Killer (NK) cells play an important role in first-line, innate defense against viral infection and tumor transformation. Their activation is the net result of signals emanating of inhibitory and activating receptors, among which the NKG2D activating receptor plays a major role. We evaluated the innate immunity of 15 patients with MPSs types I, II, IV and VI and performed the immunophenotyping of NK cells and the NKG2D receptors expression by Flow Cytometry. All MPSs patients have NK cells deficiency and decreased NKG2D receptors expression on NK cells in 2 patients. We report here that MPSs patients have a deficiency of innate immunity with NK cells deficiency. To the best of our knowledge, these findings have not been previously described.- Tegumentary manifestations of Noonan and Noonan-related syndromes(2013) QUAIO, Caio Robledo D'Angioli Costa; ALMEIDA, Tatiana Ferreira de; BRASIL, Amanda Salem; PEREIRA, Alexandre C.; JORGE, Alexander A. L.; MALAQUIAS, Alexsandra C.; KIM, Chong Ae; BERTOLA, Debora RomeoOBJECTIVES: Noonan and Noonan-related syndromes are common autosomal dominant disorders with neuro-cardio-facial-cutaneous and developmental involvement. The objective of this article is to describe the most relevant tegumentary findings in a cohort of 41 patients with Noonan or Noonan-related syndromes and to detail certain aspects of the molecular mechanisms underlying ectodermal involvement. METHODS: A standard questionnaire was administered. A focused physical examination and a systematic review of clinical records was performed on all patients to verify the presence of tegumentary alterations. The molecular analysis of this cohort included sequencing of the following genes in all patients: PTPN1, SOS1, RAF1, KRAS, SHOC2 and BRAF. RESULTS: The most frequent tegumentary alterations were xeroderma (46%), photosensitivity (29%), excessive hair loss (24%), recurrent oral ulcers (22%), curly hair (20%), nevi (17%), markedly increased palmar and plantar creases (12%), follicular hyperkeratosis (12%), palmoplantar hyperkeratosis (10%), cafe-au-lait spots (10%) and sparse eyebrows (7%). Patients with mutations in PTPN11 had lower frequencies of palmar and plantar creases and palmar/plantar hyperkeratosis compared with the other patients. CONCLUSIONS: We observed that patients with mutations in genes directly involved in cell proliferation kinase cascades (SOS1, BRAF, KRAS and RAF1) had a higher frequency of hyperkeratotic lesions compared with patients with mutations in genes that have a more complex interaction with and modulation of cell proliferation kinase cascades (PTPN11).
- Clinical description of 41 Brazilian patients with oculo-auriculo-vertebral dysplasia(2016) PEGLER, José Roberto Mendes; SOARES, Diogo Cordeiro de Queiroz; QUAIO, Caio Robledo D’Angioli Costa; FERNANDES, Natalia; OLIVEIRA, Luiz Antonio Nunes de; HONJO, Rachel Sayuri; BERTOLA, Debora Romeo; KIM, Chong AeSUMMARY Objective: To describe the most prominent clinical features of a cohort of patients with oculo-auriculo-vertebral (OAV) dysplasia in Brazil. Method: A review of medical records of patients with diagnosis of OAV from 1990 to 2010 was performed in a medical genetics center. Results: 41 patients were included in the study. Their average age at diagnosis was 2y 10mo (34,4±48,8 months) and the female proportion was 53.7%. Mean maternal age at patient’s birth was 28.5y (min: 17, max: 46y) for mothers and 31.4y (min: 21, max: 51y) for fathers. Most patients (97.5%) had auricular involvement, with facial manifestation in 90.2%, spinal in 65.9%, ocular in 53.7%, 36.6% with cardiovascular involvement, 29.3% urogenital, and 17% of the cases with central nervous system (CNS) involvement. The classic OAV triad was present in only 34%. All patients except one had concomitant problems in other organs or systems. Conclusion: Since the diagnosis of OAV dysplasia relies only on a comprehensive medical evaluation, it is imperative that clinicians be aware of the most common presentation of the syndrome. Once suspected, every patient should undergo a complete medical evaluation of multiple systems including complementary exams. Treatment of these patients is based on surgical correction of malformations and rehabilitation.