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  1. Article ; Online: Demographic, clinical, and ancestry characterization of a large cluster of mucopolysaccharidosis IV A in the Brazilian Northeast region.

    Dos Santos-Lopes, Simone Silva / de Oliveira, Jessica Maria Florêncio / de Queiroga Nascimento, Denise / Montenegro, Yorran Hardman Araújo / Leistner-Segal, Sandra / Brusius-Facchin, Ana Carolina / Eufrazino Gondim, Cátia / Giugliani, Roberto / de Medeiros, Paula Frassinetti Vasconcelos

    American journal of medical genetics. Part A

    2021  Volume 185, Issue 10, Page(s) 2929–2940

    Abstract: Mucopolysaccharidosis (MPS) IVA is a rare autosomal recessive disease with a highly variable distribution worldwide. Discrepancies in the incidence of MPS IVA among populations of different ethnicities are mostly attributed to founder effects. ... ...

    Abstract Mucopolysaccharidosis (MPS) IVA is a rare autosomal recessive disease with a highly variable distribution worldwide. Discrepancies in the incidence of MPS IVA among populations of different ethnicities are mostly attributed to founder effects. Demographic and clinical data from 28 MPS IVA patients, followed at a single center, and ancestry (Y chromosome and mitochondrial markers) of a subsample of 17 patients, most with the p.Ser341Arg (c.1023C>G) mutation were analyzed. Parental consanguinity was observed in 15/20 couples; a rare homozygous N-acetylgalactosamine-6-sulfatase (GALNS) mutation was found in 7/16 families with intra-familial phenotypic heterogeneity. Paternal ancestry was 94.2% (16/17) European, 5.8% (1/17) African, and 0% Amerindian. The European paternal haplogroups R1a, R1b, and R* accounted for 94.2% (16/17) of the patients. The R1b haplogroup, identified in 59% (10/17) of the patients, is frequently found in populations from the Iberian Peninsula. European, Amerindian, and African maternal ancestry was observed in 46.9% (8/17), 35.4% (6/17), and 17.7% (3/17) of the patients, respectively. Study of a cluster of MPS IVA patients from Northeastern Brazil, with high parental consanguinity and phenotypic heterogeneity showed predominantly European parental ancestry. This ancestry finding corroborates historical data on the local settlement, formed predominantly by European men.
    MeSH term(s) Adolescent ; Adult ; Amino Acid Sequence/genetics ; Blacks/genetics ; Brazil/epidemiology ; Child ; Chondroitinsulfatases/genetics ; Chromosomes, Human, Y ; Consanguinity ; DNA, Mitochondrial/genetics ; Demography/statistics & numerical data ; Female ; Genetic Heterogeneity ; Haplotypes/genetics ; Humans ; Male ; Middle Aged ; Mucopolysaccharidosis IV/epidemiology ; Mucopolysaccharidosis IV/genetics ; Mucopolysaccharidosis IV/pathology ; Mutation, Missense ; Young Adult
    Chemical Substances DNA, Mitochondrial ; Chondroitinsulfatases (EC 3.1.6.-) ; GALNS protein, human (EC 3.1.6.4)
    Language English
    Publishing date 2021-06-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2108614-X
    ISSN 1552-4833 ; 0148-7299 ; 1552-4825
    ISSN (online) 1552-4833
    ISSN 0148-7299 ; 1552-4825
    DOI 10.1002/ajmg.a.62375
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  2. Article ; Online: Achondroplasia in Latin America: practical recommendations for the multidisciplinary care of pediatric patients.

    Llerena, Juan / Kim, Chong Ae / Fano, Virginia / Rosselli, Pablo / Collett-Solberg, Paulo Ferrez / de Medeiros, Paula Frassinetti Vasconcelos / Del Pino, Mariana / Bertola, Débora / Lourenço, Charles Marques / Cavalcanti, Denise Pontes / Félix, Têmis Maria / Rosa-Bellas, Antonio / Rossi, Norma Teresa / Cortes, Fanny / Abreu, Flávia / Cavalcanti, Nicolette / Ruz, Maria Cecilia Hervias / Baratela, Wagner

    BMC pediatrics

    2022  Volume 22, Issue 1, Page(s) 492

    Abstract: Background: Achondroplasia is the most common bone dysplasia associated with disproportionate short stature, and other comorbidities, such as foramen magnum stenosis, thoracolumbar kyphosis, lumbar hyperlordosis, genu varum and spinal compression. ... ...

    Abstract Background: Achondroplasia is the most common bone dysplasia associated with disproportionate short stature, and other comorbidities, such as foramen magnum stenosis, thoracolumbar kyphosis, lumbar hyperlordosis, genu varum and spinal compression. Additionally, patients affected with this condition have higher frequency of sleep disorders, ear infections, hearing loss and slowed development milestones. Considering these clinical features, we aimed to summarize the regional experts' recommendations for the multidisciplinary management of patients with achondroplasia in Latin America, a vast geographic territory with multicultural characteristics and with socio-economical differences of developing countries.
    Methods: Latin American experts (from Argentina, Brazil, Chile and Colombia) particiáted of an Advisory Board meeting (October 2019), and had a structured discussion how patients with achondroplasia are followed in their healthcare centers and punctuated gaps and opportunities for regional improvement in the management of achondroplasia.
    Results: Practical recommendations have been established for genetic counselling, prenatal diagnosis and planning of delivery in patients with achondroplasia. An outline of strategies was added as follow-up guidelines to specialists according to patient developmental phases, amongst them neurologic, orthopedic, otorhinolaryngologic, nutritional and anthropometric aspects, and related to development milestones. Additionally, the role of physical therapy, physical activity, phonoaudiology and other care related to the quality of life of patients and their families were discussed. Preoperative recommendations to patients with achondroplasia were also included.
    Conclusions: This study summarized the main expert recommendations for the health care professionals management of achondroplasia in Latin America, reinforcing that achondroplasia-associated comorbidities are not limited to orthopedic concerns.
    MeSH term(s) Achondroplasia/diagnosis ; Achondroplasia/genetics ; Achondroplasia/therapy ; Child ; Female ; Genetic Counseling ; Humans ; Kyphosis ; Latin America/epidemiology ; Quality of Life
    Language English
    Publishing date 2022-08-19
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2041342-7
    ISSN 1471-2431 ; 1471-2431
    ISSN (online) 1471-2431
    ISSN 1471-2431
    DOI 10.1186/s12887-022-03505-w
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  3. Article ; Online: Evaluation of oral manifestations of patients with mucopolysaccharidosis IV and VI: clinical and imaging study.

    de Almeida-Barros, Renata Quirino / de Medeiros, Paula Frassinetti Vasconcelos / de Almeida Azevedo, Marcella Quirino / de Oliveira Lira Ortega, Adriana / Yamamoto, Angela Toshie Araki / Dornelas, Sheyla Kátia Lúcio / Bento, Patrícia Meira

    Clinical oral investigations

    2017  Volume 22, Issue 1, Page(s) 201–208

    Abstract: Objective: The aim of this study is to assess oral manifestations in patients with mucopolysaccharidosis IV (MPS IVA) and mucopolysaccharidosis VI (MPS VI).: Materials and methods: Seventeen patients were assessed, nine with MPS IVA and eight with ... ...

    Abstract Objective: The aim of this study is to assess oral manifestations in patients with mucopolysaccharidosis IV (MPS IVA) and mucopolysaccharidosis VI (MPS VI).
    Materials and methods: Seventeen patients were assessed, nine with MPS IVA and eight with MPS VI, treated at the Medical Genetics Outpatient Clinic of Hospital Universitário Alcides Carneiro (HUAC) in Campina Grande, Paraíba State, Brazil. Assessments included clinical and intraoral examinations, analysis of occlusal function, and panoramic X-rays.
    Results: Among all, 64.7% of the patients had unerupted teeth and 52.9% of them had enamel hypoplasia. Regarding the temporomandibular joint, 88.2% of the patients showed flattening of the mandibular condyle, 52.9% showed condylar hypoplasia, and all of them showed decreased mobility. Enamel hypoplasia was observed only in patients with MPS IVA (p < 0.05). On the other hand, only MPS VI patients presented with anterior open bite, restricted mouth opening (p < 0.05), and a higher rate of unerupted teeth, hyperplastic tooth follicle, and condylar defects (p < 0.05).
    Conclusions: Enamel hypoplasia was observed only in patients with MPS IVA, whereas anterior open bite was observed only in patients with MPS VI. Abnormal findings in the maxillomandibular complex were more frequent in patients with MPS VI.
    Clinical relevance: The relevant frequency of MPS VI and IVA in the sample allows us to compare the changes occurring in both groups of patients, therefore enabling us to further comprehend the oral manifestations in specific types of MPS.
    MeSH term(s) Adolescent ; Adult ; Child ; Cross-Sectional Studies ; Female ; Humans ; Male ; Mouth Diseases/diagnosis ; Mouth Diseases/etiology ; Mucopolysaccharidosis IV/complications ; Mucopolysaccharidosis VI/complications ; Radiography, Panoramic
    Language English
    Publishing date 2017-03-19
    Publishing country Germany
    Document type Journal Article ; Observational Study
    ZDB-ID 1364490-7
    ISSN 1436-3771 ; 1432-6981
    ISSN (online) 1436-3771
    ISSN 1432-6981
    DOI 10.1007/s00784-017-2100-8
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    Zs.A 4788: Show issues Location:
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  4. Article ; Online: Mucopolysaccharidosis VII in Brazil: natural history and clinical findings.

    Giugliani, Roberto / Barth, Anneliese Lopes / Dumas, Melissa Rossi Calvão / da Silva Franco, José Francisco / de Rosso Giuliani, Liane / Grangeiro, Carlos Henrique Paiva / Horovitz, Dafne Dain Gandelman / Kim, Chong Ae / de Araújo Leão, Emilia Katiane Embiruçu / de Medeiros, Paula Frassinetti Vasconcelos / Miguel, Diego Santana Chaves Geraldo / Moreira, Maria Espírito Santo Almeida / Dos Santos, Helena Maria Guimarães Pimentel / da Silva, Luiz Carlos Santana / da Silva, Luiz Roberto / de Souza, Isabel Neves / Nalin, Tatiele / Garcia, Daniel

    Orphanet journal of rare diseases

    2021  Volume 16, Issue 1, Page(s) 238

    Abstract: Background: Mucopolysaccharidosis type VII (MPS VII), also known as Sly syndrome, caused by deficiency of the lysosomal enzyme β-glucuronidase, is an ultra-rare disorder with scarce epidemiological data and few publications about natural history and ... ...

    Abstract Background: Mucopolysaccharidosis type VII (MPS VII), also known as Sly syndrome, caused by deficiency of the lysosomal enzyme β-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.
    MeSH term(s) Brazil/epidemiology ; Humans ; Mucopolysaccharidosis VII/genetics ; Mutation ; Retrospective Studies
    Language English
    Publishing date 2021-05-22
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ISSN 1750-1172
    ISSN (online) 1750-1172
    DOI 10.1186/s13023-021-01870-w
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  5. Article ; Online: Genotype-phenotype studies in a large cohort of Brazilian patients with Hunter syndrome.

    Josahkian, Juliana Alves / Brusius-Facchin, Ana Carolina / Netto, Alice Brinckmann Oliveira / Leistner-Segal, Sandra / Málaga, Diana Rojas / Burin, Maira Graeff / Michelin-Tirelli, Kristiane / Trapp, Franciele Barbosa / Cardoso-Dos-Santos, Augusto César / Ribeiro, Erlane Marques / Kim, Chong Ae / de Siqueira, Ana Cecília Menezes / Santos, Mara Lucia / do Valle, Daniel Almeida / da Silva, Raquel Tavares Boy / Horovitz, Dafne Dain Gandelman / de Medeiros, Paula Frassinetti Vasconcelos / de Souza, Carolina Fischinger Moura / Giuliani, Liane de Rosso /
    Miguel, Diego Santana Chaves Geraldo / Santana-da-Silva, Luiz Carlos / Galera, Marcial Francis / Giugliani, Roberto

    American journal of medical genetics. Part C, Seminars in medical genetics

    2021  Volume 187, Issue 3, Page(s) 349–356

    Abstract: Mucopolysaccharidosis type II (MPS II) is an X-linked inherited disease caused by pathogenic variants in the IDS gene, leading to deficiency of the lysosomal enzyme iduronate-2-sulfatase and consequent widespread storage of glycosaminoglycans, leading to ...

    Abstract Mucopolysaccharidosis type II (MPS II) is an X-linked inherited disease caused by pathogenic variants in the IDS gene, leading to deficiency of the lysosomal enzyme iduronate-2-sulfatase and consequent widespread storage of glycosaminoglycans, leading to several clinical consequences, with progressive manifestations which most times includes cognitive decline. MPS II has wide allelic and clinical heterogeneity and a complex genotype-phenotype correlation. We evaluated data from 501 Brazilian patients diagnosed with MPS II from 1982 to 2020. We genotyped 280 of these patients (55.9%), which were assigned to 206 different families. Point mutations were present in 70% of our patients, being missense variants the most frequent. We correlated the IDS pathogenic variants identified with the phenotype (neuronophatic or non-neuronopathic). Except for two half-brothers, there was no discordance in the genotype-phenotype correlation among family members, nor among MPS II patients from different families with the same single base-pair substitution variant. Mothers were carriers in 82.0% of the cases. This comprehensive study of the molecular profile of the MPS II cases in Brazil sheds light on the genotype-phenotype correlation and helps the better understanding of the disease and the prediction of its clinical course, enabling the provision of a more refined genetic counseling to the affected families.
    MeSH term(s) Brazil ; Genotype ; Humans ; Male ; Mucopolysaccharidosis II/genetics ; Mutation ; Phenotype
    Language English
    Publishing date 2021-05-07
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2108622-9
    ISSN 1552-4876 ; 0148-7299 ; 1552-4868
    ISSN (online) 1552-4876
    ISSN 0148-7299 ; 1552-4868
    DOI 10.1002/ajmg.c.31915
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  6. Article ; Online: Molecular analysis of the CTSK gene in a cohort of 33 Brazilian families with pycnodysostosis from a cluster in a Brazilian Northeast region.

    Araujo, Thaís Fenz / Ribeiro, Erlane Marques / Arruda, Anderson Pontes / Moreno, Carolina Araujo / de Medeiros, Paula Frassinetti Vasconcelos / Minillo, Renata Moldenhauer / Melo, Débora Gusmão / Kim, Chong Ae / Doriqui, Maria Juliana Rodovalho / Felix, Têmis Maria / Fock, Rodrigo Ambrosio / Cavalcanti, Denise Pontes

    European journal of medical research

    2016  Volume 21, Issue 1, Page(s) 33

    Abstract: Background: Pycnodysostosis is an autosomal recessive skeletal dysplasia, the prevalence of which is estimated to be low (1 per million). Nevertheless, in recent years we have found 27 affected individuals from 22 families in Ceará State, a region of ... ...

    Abstract Background: Pycnodysostosis is an autosomal recessive skeletal dysplasia, the prevalence of which is estimated to be low (1 per million). Nevertheless, in recent years we have found 27 affected individuals from 22 families in Ceará State, a region of the Brazilian Northeast, giving a local prevalence of 3 per million. This local prevalence associated with a high parental consanguinity, suggesting a possible founder effect, prompted us to perform a molecular investigation of these families to test this hypothesis.
    Methods: The CTSK gene was sequenced by the Sanger method in the patients and their parents. In addition to 18 families from Ceará, this study also included 15 families from other Brazilian regions. We also investigated the origin of each family from the birthplace of the parents and/or grandparents.
    Results: We have studied 39 patients, including 33 probands and 6 sibs, from 33 families with pycnodysostosis and identified six mutations, five previously described (c.436G>C, c.580G>A, c.721C>T, c.830C>T and c.953G>A) and one novel frameshift (c.83dupT). This frameshift variant seems to have a single origin in Ceará State, since the haplotype study using the polymorphic markers D1S2344, D1S442, D1S498 and D1S2715 suggested a common origin. Most of the mutations were found in homozygosity in the patients from Ceará (83.3 %) while in other states the mutations were found in homozygosity in half of patients. We have also shown that most of the families currently living outside of Ceará have northeastern ancestors, suggesting a dispersion of these mutations from the Brazilian Northeast.
    Conclusions: The high frequency of pycnodysostosis in Ceará State is the consequence of the high inbreeding in that region. Several mutations, probably introduced a long time ago in Ceará, must have spread due to consanguineous marriages and internal population migration. However, the novel mutation seems to have a single origin in Ceará, suggestive of a founder effect.
    MeSH term(s) Brazil ; Cathepsin K/genetics ; Female ; Founder Effect ; Homozygote ; Humans ; Male ; Mutation ; Pedigree ; Polymorphism, Genetic ; Pycnodysostosis/genetics
    Chemical Substances CTSK protein, human (EC 3.4.22.38) ; Cathepsin K (EC 3.4.22.38)
    Language English
    Publishing date 2016-08-24
    Publishing country England
    Document type Journal Article
    ZDB-ID 1329381-3
    ISSN 2047-783X ; 0949-2321
    ISSN (online) 2047-783X
    ISSN 0949-2321
    DOI 10.1186/s40001-016-0228-7
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    Zs.A 4636: Show issues Location:
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  7. Article ; Online: Oral and systemic manifestations of mucopolysaccharidosis type VI: a report of seven cases.

    de Almeida-Barros, Renata Quirino / Oka, Salomão Cury-Rad / Pordeus, Ana Carolina Barbosa / de Medeiros, Paula Frassinetti Vasconcelos / Bento, Patricia Meira / Godoy, Gustavo Pina

    Quintessence international (Berlin, Germany : 1985)

    2012  Volume 43, Issue 3, Page(s) e32–8

    Abstract: Mucopolysaccharidosis (MPS) is a group of rare metabolic diseases characterized by intralysosomal accumulation of glycosaminoglycans. MPS type VI or Maroteaux-Lamy syndrome is an autosomal-recessive syndrome caused by mutations in the lysosomal enzyme ... ...

    Abstract Mucopolysaccharidosis (MPS) is a group of rare metabolic diseases characterized by intralysosomal accumulation of glycosaminoglycans. MPS type VI or Maroteaux-Lamy syndrome is an autosomal-recessive syndrome caused by mutations in the lysosomal enzyme arylsulfatase B. A defect in the gene leads to accumulation of nondegraded mucopolysaccharides, resulting in severe cellular dysfunction with multisystem expression. The oral manifestations of MPS VI are not well described in the literature. This paper presents a series of seven patients with MPS VI, with the description of the general clinical manifestations and focus on the still rarely studied oral manifestations of the syndrome. Among them were high palate, open bite, impacted and/or included teeth, thickening of the pericoronal follicle, and changes in the temporomandibular joint.
    MeSH term(s) Adolescent ; Child ; Child, Preschool ; Dental Sac/pathology ; Diastema/etiology ; Female ; Humans ; Macroglossia/etiology ; Male ; Malocclusion/etiology ; Mouth Diseases/etiology ; Mucopolysaccharidosis VI/complications ; Open Bite/etiology ; Palate/abnormalities ; Temporomandibular Joint Disorders/etiology ; Tooth, Impacted/etiology
    Language English
    Publishing date 2012-02-02
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 7436-6
    ISSN 1936-7163 ; 0033-6572
    ISSN (online) 1936-7163
    ISSN 0033-6572
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