JOSE FRANCISCO DA SILVA FRANCO
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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.
- Mucopolysaccharidosis VII in Brazil: natural history and clinical findings(2021) GIUGLIANI, Roberto; BARTH, Anneliese Lopes; DUMAS, Melissa Rossi Calvao; FRANCO, Jose Francisco da Silva; GIULIANI, Liane de Rosso; GRANGEIRO, Carlos Henrique Paiva; HOROVITZ, Dafne Dain Gandelman; KIM, Chong Ae; LEAO, Emilia Katiane Embirucu de Araujo; MEDEIROS, Paula Frassinetti Vasconcelos de; MIGUEL, Diego Santana Chaves Geraldo; MOREIRA, Maria Espirito Santo Almeida; SANTOS, Helena Maria Guimaraes Pimentel dos; SILVA, Luiz Carlos Santana da; SILVA, Luiz Roberto da; SOUZA, Isabel Neves de; NALIN, Tatiele; GARCIA, DanielBackground Mucopolysaccharidosis type VII (MPS VII), also known as Sly syndrome, caused by deficiency of the lysosomal enzyme beta-glucuronidase, is an ultra-rare disorder with scarce epidemiological data and few publications about natural history and clinical spectrum. Methods We conducted a case series report which included retrospective data from all MPS VII patients diagnosed through the ""MPS Brazil Network"" who were known to be alive in 2020 in Brazil (N = 13). Clinical data were obtained from a review of the medical records and descriptive statistics and variables were summarized using counts and percentages of the total population. Results The majority of the patients were from the Northeast region of Brazil. Among the signs and symptoms that raised the clinical suspicion of MPS, coarse face was the most frequent; 58% of the patients had a history of non-immune hydrops fetalis. All the subjects presented short neck and trunk. The majority presented typical phenotypical signs of MPS disorders. They all presented neurodevelopmental delay and cognitive impairment. About half of this cohort had knees deformities. Dysostosis multiplex was identified in almost all patients and cardiomyopathy was less frequent than observed in other types of MPSs. The mean age at diagnosis was 5 years, ranging from 1 to 14 years. Almost all patients (12/13) were homozygous for the c.526C>T (p.Leu176Phe) mutation. A novel variant of the GUSB gene was found, the c.875T>C (p.Leu292Pro), in a compound heterozygous with the c.526C>T (p.Leu176Phe) variant. Conclusions This case series is the biggest data collection of MPS VII patients alive in Latin America. The overall clinical picture of the MPS VII patients is very similar to other MPS disorders, including a spectrum of severity and delayed diagnosis.
- 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.
- Impact of early enzyme-replacement therapy for mucopolysaccharidosis VI: results of a long-term follow-up of Brazilian siblings(2016) FRANCO, J. F.; SOARES, D. C.; TORRES, L. C.; LEAL, G. N.; CUNHA, M. T.; HONJO, R. S.; BERTOLA, D. R.; KIM, C. A.Mucopolysaccharidosis type VI (MPS VI) is an autosomal recessive multisystem lysosomal storage disorder, which is characterized by the deficiency of the enzyme arylsulfatase B encoded by the ARSB gene. Treatment of this disease with enzyme-replacement therapy (ERT) improves the clinical status of and generates hope for MPS VI patients. However, only few reports on patients with MPS VI treated before 5 years of age have been published. Thus, the objective of this study was to compare the clinical parameters of two sisters affected by MPS VI who started ERT at different ages (9 years and 1 year 5 months, respectively) and to determine the most relevant clinical impacts of early treatment after 85 months of evaluation. The treatment was well tolerated by both siblings. ERT in the younger sibling resulted in increased growth, an improved 6-minute walk test, less coarse face, slower progression of cardiac valve disease, and the absence of compressive myelopathy compared to that in her older sister. On the other hand, the older sibling had typical MPS VI phenotypic features before the commencement of ERT. Corneal clouding, clawed hands, and progressive skeletal changes were observed in both siblings despite the treatment. Both siblings displayed reduced frequencies of upper respiratory infections and apnea indices. This study emphasizes that early diagnosis and treatment of MPS VI are critical for a better disease outcome and to enhance the quality of life for these patients.
- NK and B cell deficiency in a MPS type II family with novel mutation in the IDS gene(2014) TORRES, Leuridan Cavalcante; SOARES, Diogo Cordeiro de Queiroz; KULIKOWSKI, Leslie Domenici; FRANCO, Jose Francisco; KIM, Chong AeThe mucopolysaccharidoses (MPSs) are a group of rare, inherited lysosomal storage disorders that are clinically characterized by abnormalities in multiple organ systems and reduced life expectancy. Whereas the lysosome is essential to the functioning of the immune system, some authors suggest that the MPS patients have abnormalities in the immune system similar to the patients with primary immunodeficiency. In this study, we evaluated 8 male MPS type II patients of the same family with novel mutation in the IDS gene. We found in this MPS family a quantitative deficiency of NK and B cells with normal values of IgG, IgM and IgA serum antibodies and normal response to polysaccharide antigens. Interestingly, abnormalities found in these patients were not observed in other MPS patients, suggesting that the type of mutation found in the IDS gene can be implicated in the immunodeficiency.
- Wiedemann-Rautenstrauch syndrome: A phenotype analysis(2017) PAOLACCI, Stefano; BERTOLA, Debora; FRANCO, Jose; MOHAMMED, Shehla; TARTAGLIA, Marco; WOLLNIK, Bernd; HENNEKAM, Raoul C.Wiedemann-Rautenstrauch syndrome (WRS) is a neonatal progeroid disorder characterized by growth retardation, lipodystrophy, a distinctive face, and dental anomalies. Patients reported to date demonstrate a remarkable variability in phenotype, which hampers diagnostics. We performed a literature search, and analyzed 51 reported patients, using the originally reported patients as ""gold standard."" In 15 patients sufficient information and photographic evidence was available to confirm the clinical diagnosis. In 12 patients the diagnosis was suggestive but lack of data prevented a definite diagnosis, and in 24 patients an alternative diagnosis was likely. Core manifestations of the syndrome are marked pre-natal and severe post-natal growth retardation, an unusual face (triangular shape, sparse hair, small mouth, pointed chin), dental anomalies (natal teeth; hypodontia), generalized lipodystrophy with localized fat masses, and-in some cases-progressive ataxia and tremor. It has been suggested that the syndrome might be caused by biallelic variants in POLR3A, identified by exome sequencing in a single patient only. Therefore, we compared the WRS phenotype with characteristics of conditions known to be caused by autosomal recessively inherited POLR3A mutations. There are major differences but there are also similarities in phenotype, which sustain the suggestion that the syndrome can be caused by disturbed POLR3A functioning.