RESUMO
Eleven patients from Yakutia with a new lysosomal disease assumed then as mucopolysaccharidosis-plus syndrome (MPS-PS) were reported by Gurinova et al. in 2014. Up to now, a total number of 39 patients have been reported; in all of them, the c.1492C>T (p.Arg498Trp) variant of the VPS33A gene was detected. Here, we describe the first Polish MPS-PS patient with a novel homozygous c.599G>C (p.Arg200Pro) VPS33A variant presenting over 12 years of follow-up with some novel clinical features, including fetal ascites (resolved spontaneously), recurrent joint effusion and peripheral edemas, normal growth, and visceral obesity. Functional analyses revealed a slight presence of chondroitin sulphate (only) in urine glycosaminoglycan electrophoresis, presence of sialooligosaccharides in urine by thin-layer chromatography, and normal results of lysosomal enzymes activity and lysosphingolipids concentration in dried blood spot. The comparison with other MPS-PS described cases was also provided. The presented description of the natural history of MPS-PS in our patient may broaden the spectrum of phenotypes in this disease.
Assuntos
Mucopolissacaridoses , Proteínas de Transporte Vesicular , Sulfatos de Condroitina/urina , Glicosaminoglicanos/urina , Humanos , Mucopolissacaridoses/sangue , Mucopolissacaridoses/diagnóstico , Mucopolissacaridoses/genética , Mucopolissacaridoses/urina , Mutação , Polônia , Esfingolipídeos/sangue , Proteínas de Transporte Vesicular/genéticaRESUMO
Glutaric aciduria type 1 is a neurometabolic disorder, caused by riboflavin-dependent glutaryl-CoA dehydrogenase deficiency. As its consequence, accumulation of the putatively neurotoxic metabolites (glutaric and 3-hydroxyglutaric acids) in body tissues, but especially within the brain, is observed. Estimated incidence of the disease is 1 in 110,000 newborns, The prevalence however may be higher, depending on a specific ethnic group, and result in phenotypic variation as well. In this paper we present clinical data of 13 patients of Polish nationality. They all present a mild phenotype and clinical course of glutaric aciduria type 1. Based on their clinical data, presented herein, we like to pay attention to the phenotypic and neuroimaging features important for the diagnosis of mild form of this disease. Moreover, we present novel molecular data, which may correlate with such a manifestation.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Encefalopatias Metabólicas/diagnóstico , Encéfalo/diagnóstico por imagem , Glutaril-CoA Desidrogenase/deficiência , Neuroimagem , Fenótipo , Encéfalo/metabolismo , Feminino , Glutaratos/metabolismo , Humanos , Recém-Nascido , Masculino , PolôniaRESUMO
BACKGROUND: Resistance to thyroid hormone is characterised by a lack of response of peripheral tissues to the active form of thyroid hormone (triiodothyronine, T3). In about 85% of cases, a mutation in THRB, the gene coding for thyroid receptor ß (TRß), is the cause of this disorder. Recently, individual reports described the first patients with thyroid hormone receptor α gene (THRA) defects. METHODS: We used longitudinal clinical assessments over a period of 18 years at one hospital setting combined with biochemical and molecular studies to characterise a novel thyroid hormone resistance syndrome in a cohort of six patients from five families. FINDINGS: Using whole exome sequencing and subsequent Sanger sequencing, we identified truncating and missense mutations in the THRA gene in five of six individuals and describe a distinct and consistent phenotype of mild hypothyroidism (growth retardation, relatively high birth length and weight, mild-to-moderate mental retardation, mild skeletal dysplasia and constipation), specific facial features (round, somewhat coarse and flat face) and macrocephaly. Laboratory investigations revealed anaemia and slightly elevated cholesterol, while the thyroid profile showed low free thyroxine (fT4) levels coupled with high free T3 (fT3), leading to an altered T4 : T3 ratio, along with normal thyroid-stimulating hormone levels. We observed a genotype-phenotype correlation, with milder outcomes for missense mutations and more severe phenotypical effects for truncating mutations. INTERPRETATION: THRA mutations may be more common than expected. In patients with clinical symptoms of mild hypothyreosis without confirmation in endocrine studies, a molecular study of THRA defects is strongly recommended.
Assuntos
Estudos de Associação Genética , Mutação , Receptores alfa dos Hormônios Tireóideos/genética , Síndrome da Resistência aos Hormônios Tireóideos/genética , Adolescente , Adulto , Criança , Pré-Escolar , Análise Mutacional de DNA , Fácies , Feminino , Genótipo , Humanos , Masculino , Fenótipo , Síndrome da Resistência aos Hormônios Tireóideos/diagnóstico , Síndrome da Resistência aos Hormônios Tireóideos/tratamento farmacológico , Tiroxina , Falha de Tratamento , Adulto JovemRESUMO
BACKGROUND: The aim of this study was to describe the natural clinical course, incidence and prevalence of mucopolysaccharidosis type VI (MPS VI) in Russia, Kazakhstan, and Central and Eastern Europe. METHODS: Patients (n = 49) were identified by retrieving the data from eight international centers for MPS VI. RESULTS: A large number of patients presented with an attenuated phenotype (33%). Height and genotype were related to the severity of the disease, while no clear trend was observed between height and urinary glycosaminoglycan level. A high prevalence of the p.R152W mutation was observed both in the whole series (42%) as well as in Russian patients (43%). The incidence rate ranged from 0.0363 to 0.64 per 100,000 live births in Poland and Lithuania, respectively. CONCLUSIONS: The observed high p.R152W carrier frequency in the Lithuanian population may indicate a possible founder effect in this region. The high prevalence of this mutation observed in the whole series, as well as the Slavic origin of the majority of patients homozygous for this mutation, suggest that p.R152W may be of Slavic, not Lithuanian origin. Resettlement of the Polish population after World War II resulted in dilution of the prevalence of carriers in Poland and a very low MPS VI incidence.
Assuntos
Mucopolissacaridose VI , Criança , Pré-Escolar , Europa (Continente)/epidemiologia , Feminino , Humanos , Incidência , Cazaquistão/epidemiologia , Masculino , Mucopolissacaridose VI/diagnóstico , Mucopolissacaridose VI/epidemiologia , Mucopolissacaridose VI/genética , Mutação , Fenótipo , Prevalência , Federação Russa/epidemiologiaRESUMO
UNLABELLED: Growth references are useful in monitoring a child's growth, which is an essential part of child care. The aim of this paper is to provide updated growth references for Polish preschool children and to assess how well children in Poland match or diverge from the World Health Organization (WHO) growth standards/references and recent German height-for-age references. The height-, weight-, body mass index-for-age, and weight-for-height references were constructed with the LMS method using data from a recent, large, population-representative sample of 4,941 preschool children aged 3 to 6 years (the OLA study). In the case of boys, the third, 50th, and 97th height percentiles of new Polish and German references overlap almost completely, whereas the WHO growth standards/references percentiles are systematically lower. In the case of girls, comparison between the new Polish and German height references showed conformity on the third and 50th percentile, whereas body height values of the WHO standards/references are shorter. Polish children aged 3 to 6 years from for the nation representative sample, had significantly greater than zero mean z scores of height-, weight-, and BMI-for-age and weight-for-height, relative to the WHO growth standards/references. The number of children in the sample with height-for-age below -2 SD was significantly lower than expected and number of children with height-for-age above +2 SD was significantly higher than expected. CONCLUSION: The OLA study growth references can be recommended as national references for preschool children in Poland.
Assuntos
Estatura , Índice de Massa Corporal , Peso Corporal , Gráficos de Crescimento , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Masculino , Modelos Estatísticos , Polônia , Organização Mundial da SaúdeRESUMO
Objective: This study assessed growth patterns in patients with mucopolysaccharidosis (MPS) VII before enzyme replacement therapy. Methods: Height, weight, and body mass index (BMI) measurements and Z-scores from patients from three clinical studies were compared with those from CDC healthy population growth charts. Relationships with age/sex and history of non-immune hydrops fetalis (NIHF) were assessed by linear regression and ANOVA, respectively. Results: Among 20 enrolled patients with MPS VII, height Z-scores were near normal until 1 year of age but declined thereafter, particularly among males. There was no consistent pattern in weight Z-score. BMI Z-scores were above normal and increased slightly with age among males and were slightly below normal among females. Male patients with a history of NIHF had greater declines in height and weight Z-scores over time versus males without history of NIHF. There was no clear effect of NIHF history on height and weight Z-scores in female patients. Conclusions: In patients with MPS VII, declines in height Z-score began early in life, particularly among males, while changes in BMI varied by sex. Patients with MPS VII and a history of NIHF had greater declines in height Z-score with age than did patients without a history of NIHF.Clinical trial registration: This retrospective analysis included patients enrolled in an open-label phase 2 study (UX003-CL203; ClinicalTrials.gov, NCT02418455), a randomized, placebo-controlled, blind-start phase 3 study (UX003-CL301; ClinicalTrials.gov, NCT02230566), or its open-label, long-term extension (UX003-CL202; ClinicalTrials.gov, NCT02432144). Requests for individual de-identified participant data and the clinical study report from this study are available to researchers providing a methodologically sound proposal that is in accordance with the Ultragenyx data sharing commitment. To gain access, data requestors will need to sign a data access and use agreement. Data will be shared via secured portal. The study protocol and statistical analysis plan for this study are available on the relevant clinical trial registry websites with the tabulated results.
RESUMO
Mucopolysaccharidosis type II (MPS II, Hunter syndrome) is an X-linked lysosomal storage disease caused by a deficiency of iduronate-2-sulfatase (IDS). Two affected girls with moderate and severe forms of MPS II with normal karyotypes and increased urinary dermatan sulphate and heparin sulphate excretion and marked deficiencies of IDS activity are reported. Molecular studies showed that case 1 has a heterozygous mutation c.1568A > G (p.Y523C) associated with almost totally skewed inactivation of the normal maternal X chromosome, and case 2 has a heterozygous deletion that includes exons 1-4 of IDS (minimal deletion range c.1-103_184del). The multi-exon deletion correlated with early onset of the disease and severe phenotype with intellectual disability, whereas the missense mutation was associated with moderate developmental delay. Although genotype-phenotype correlation in MPS II is difficult, gene deletions seem to correlate with more severe clinical manifestation of the disease. Enzyme replacement therapy (ERT) in these two females resulted in disease stabilization in both.
Assuntos
Terapia de Reposição de Enzimas , Iduronato Sulfatase/genética , Iduronato Sulfatase/uso terapêutico , Mucopolissacaridose II/enzimologia , Mucopolissacaridose II/genética , Mucopolissacaridose II/terapia , Criança , Pré-Escolar , Dermatan Sulfato/urina , Feminino , Heparina/urina , Heterozigoto , Humanos , Iduronato Sulfatase/metabolismo , Mucopolissacaridose II/diagnóstico , Mucopolissacaridose II/patologia , MutaçãoRESUMO
AIM: The aims of the study were to assess shoulder range of motion (ROM) in patients with mucopolysaccharidosis type II (MPS II) and to correlate joint mobility with patients' height, age and functional status. METHODS: Passive ROM and Z-score of height were followed in 29 patients with MPS II (mean age 11.5 years, range 2-29 years) between the years 2005 and 2010. Passive ROM was measured by a goniometer, and height, by a stadiometer. Functional status was assessed by an age-appropriate health assessment questionnaire (HAQ). RESULTS: (i) A strong correlation was observed between patients' age and Z-score of patients' height (R = 0.78, p < 0.001). (ii) A medium correlation was observed between Z-score of patients' height and passive shoulder flexion and abduction (R = 0.697, p < 0.001 and R = 0.63, p < 0.001, respectively). The progression of restriction was slower in attenuated patients. (iii) Restrictions in shoulder flexion and abduction were already observed before the second year of life. (iv) ROM limitations intensified and became more severe with age. (v) Activities of daily living depended on cognitive impairment of patients with MPS II. CONCLUSION: Range of motion limitations in patients with MPS II correlate with patients' height, increase with patients' age and are more pronounced in a severe form of MPS II.
Assuntos
Atividades Cotidianas , Estatura , Mucopolissacaridose II/fisiopatologia , Amplitude de Movimento Articular/fisiologia , Articulação do Ombro/fisiopatologia , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Feminino , Seguimentos , Inquéritos Epidemiológicos , Humanos , Masculino , Adulto JovemRESUMO
BACKGROUND: Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by deficient activity of enzymes responsible for the catabolism of glycosaminoglycans (GAGs), resulting in progressive damage to various tissues and organs. Affected individuals present with skeletal deformities, bone growth impairment, joint stiffness and frequently mental retardation. RESULTS: The objective of the study was to summarise over 30 years of observations of the growth dynamics in patients with different types of MPS, performed at the Children's Memorial Health Institute (CMHI, Warsaw, Poland). A retrospective analysis of anthropometric data collected from 1989 to 2020 was performed for 195 patients with MPS I, MPS II, MPS III, MPS IVA and MPS VI. Mean values for birth body length were statistically significantly greater than in the general population. The mean z-scores for other MPS groups showed that until the 24th month of life, the growth pattern for all patients was similar, and the average z-scores for body height were greater than in reference charts. Afterwards, growth patterns began to differentiate for MPS groups. CONCLUSIONS: The long-term follow up showed that the growth pattern in patients with all types of mucopolysaccharidoses significantly deviates from the general population. Patients with MPS IVA had the most severe growth impairments compared to other patients in the study group. Neuropathic MPS I and II demonstrated severe growth impairments compared to other patients in this study. Patients with MPS III showed the mildest growth impairments compared to other MPS patients and reached the 3rd percentile last.
Assuntos
Mucopolissacaridoses , Mucopolissacaridose III , Mucopolissacaridose IV , Mucopolissacaridose I , Mucopolissacaridose VI , Criança , Humanos , Estudos RetrospectivosRESUMO
Congenital Disorders of Glycosylation (CDG) are multisystemic metabolic disorders showing highly heterogeneous clinical presentation, molecular etiology, and laboratory results. Here, we present different transferrin isoform patterns (obtained by isoelectric focusing) from three female patients harboring the ALG13 c.320A>G mutation. Contrary to other known variants of type I CDGs, where transferrin isoelectric focusing revealed notably increased asialo- and disialotransferrin fractions, a normal glycosylation pattern was observed in the probands. To verify this data and give novel insight into this variant, we modeled the human Alg13 protein and analyzed the dynamics of the apo structure and the complex with the UDP-GlcNAc substrate. We also modeled the Alg13-Alg14 heterodimer and ran multiple simulations of the complex in the presence of the substrate. Finally, we proposed a plausible complex formation mechanism.
Assuntos
Defeitos Congênitos da Glicosilação , Variação Biológica da População , Defeitos Congênitos da Glicosilação/genética , Feminino , Glicosilação , Humanos , Mutação , N-AcetilglucosaminiltransferasesRESUMO
INTRODUCTION: Alpha-mannosidosis (AM) is a rare autosomal recessive lysosomal storage disease which the natural history has not been exhaustively described yet. The aim of this study was to present the long-term follow-up of 12 Polish patients with AM, evaluate the clinical, biochemical, and molecular findings and progression of the disease. MATERIAL AND METHODS: The article presents a long-term (over 30 years) observational, retrospective, single-center study of patients with AM. RESULTS: The hearing loss, as one of the first symptoms, was detected in childhood (mean age of 2 years and 6 months) in 10 patients. The other symptoms include: recurrent infections (all patients), inguinal hernias (6 patients), craniosynostosis (1 patient). The mean age at AM diagnosis was 6 years while median was 4 years (age range: 1 year and 8 months - 12 years). The most commonly identified variant in the MAN2B1 gene was c.2245C > T, p.(Arg749Trp). The mean time of follow-up in our study was approximately 14 years (range: 1 year - 26 years). Following birth, children with AM grow slowly, finally reaching the 3rd percentile (or values below the 3rd percentile). Hearing loss was not progressive while a gradual exacerbation of intellectual disability with no developmental regression was observed in all patients. Ataxia was diagnosed in 6 patients in the second decade of life (age range 15-20 years). CONCLUSIONS: Our study revealed the sensorineural hearing loss as one of the first noted symptom in AM which was congenital and non-progressive during the natural course of disease. A detailed anthropometric phenotype of AM patients was provided with observation of the growth decline during the long-term follow-up. Our study confirmed the existence of two distinguished clinical phenotypes of AM (mild and moderate), and also the lack of clear genotype-phenotype correlation.
RESUMO
BACKGROUND: Growth failure is commonly reported in children with PMM2-CDG. The aim of the study was to delineate the longitudinal anthropometric phenotype of patients with PMM2-CDG and attempt to find some correlations between the genotype and anthropometric phenotype. MATERIALS AND METHODS: Retrospective chart review of PMM2-CDG patients' medical records was performed regarding the anthropometric measurements (head circumference, body length/height, body weight, body mass index) and PMM2 variants. RESULTS: A negative tendency of growth evolution was observed. Patients found to be heterozygous for R141H grew slower than other patients. Body weight was correlated with body height. A negative tendency of the growth rate of head circumference was observed. Patients found to be heterozygous for R141H experienced slower growth than other patients. CONCLUSIONS: Long-term observational studies are essential to characterize the anthropometric phenotype. The body growth failure, as well as head circumference growth failure, were more severe in patients found to be heterozygous for R141H.
RESUMO
Our study aims to delineate the syndromology of Hunter syndrome (MPSII), by presenting three patients with different clinical courses, caused by different genetic mechanisms. Single-nucleotide variants (SNV) or small deletions encompassing the iduronate-2-sulfatase (IDS) gene are identified in the majority of affected individuals, while deletion of contiguous genes or whole IDS gene (described herein) has been reported rarely, mainly in patients with a severe Hunter syndrome presentation. There is; however, lack of reliable genotype-phenotype correlation, especially regarding anthropometric parameters, and thus our understanding of MPSII pathophysiology is not complete. On the basis of our observations, we would like to draw attention to the fact that neurological manifestations observed in patients with contiguous gene deletions, encompassing the IDS gene, may significantly differ from those observed in SNV. The phenotype is; however, difficult to predict and depends on the type (deletion/duplication), size (small/large) of aberration, and gene content. Moreover, it also has implications for genetic counseling, and recurrence risk in those families differs from the usual situation and must be clarified by parental chromosomal studies.
Assuntos
Aberrações Cromossômicas , Estudos de Associação Genética , Glicoproteínas/genética , Mucopolissacaridose II/diagnóstico , Mucopolissacaridose II/genética , Fenótipo , Deleção de Sequência , Alelos , Pesos e Medidas Corporais , Hibridização Genômica Comparativa , Aconselhamento , Diagnóstico Precoce , Genótipo , Humanos , Lactente , MasculinoRESUMO
BACKGROUND: Morquio A syndrome or mucopolysaccharidosis (MPS) IVA is an autosomal recessive, life-limiting lysosomal storage disease caused by deficient activity of the enzyme galactosamine-6-sulfatase. Common early symptoms such as abnormalities of body stature can facilitate timely diagnosis. This study aimed to create a pattern of face and body stature based on anthropometric measurements taken from a cohort of Polish patients with MPS IVA. METHODS: Analysis of 11 somatometric and 14 craniofacial features was performed on 20 patients with MPS IVA, aged from 3 months to 26 years. The diagnosis of MPS IVA was confirmed by enzymatic and molecular analysis. Two-tailed t-tests were used to compare mean values for body length and weight at birth between the MPS IVA patients and the general population. To show the degree and direction of deviation z-scores were calculated and then used to construct a model of an average MPS IVA patient. RESULTS: Mean values for body height and weight at birth were greater for boys than for the general population. The observed pattern of head and body shape indicated that dwarfism occurred with age as a result of the relatively short trunk and lower limbs. Skeletal abnormalities included a bell-shaped chest with the ratio of chest depth to chest width being significantly above the norm. The head and neck were relatively elongated, in comparison to body height, and tucked between narrow shoulders. The head had dolichocephalic shape, while the nose was short with wide nostrils. CONCLUSIONS: Multiple anthropometric measurements, including age ranges, allowed for the creation of a model that showed the most characteristic features of the MPS IVA phenotype.
RESUMO
OBJECTIVES: Together with the lysosomal storage diseases, NGLY1 deficiency is a congenital disorder of deglycosylation (NGLY1-CDDG). Since the first report in 2012, 26 patients have been described. All but one were diagnosed by exome or genome sequencing; the remaining one was identified by finding an increased concentration of an urinary marker.The aim of this study was to describe the clinical, biochemical, and molecular features of the first Polish patient diagnosed with NGLY1-CDDG, to provide an overview of the literature and to propose a diagnostic algorithm. RESULTS: A Polish patient presented with global developmental delay, hyperkinetic movement disorder, stagnation of head growth, hypolacrimia, elevated serum transaminases, and hypolipidemia in infancy. Whole exome sequencing revealed two heterozygous nonsense variants in the NGLY1 gene (a novel and an unreported). Literature review revealed global developmental disability in all reported patients, and hyperkinetic movements as well as alacrima/hypolacrima in nearly all. CONCLUSIONS: NGLY1-CDDG should be considered in patients with developmental disability associated with a hyperkinetic movement disorder and alacrimia/hypolacrima. Absence of the latter two symptoms does not rule out this diagnosis.
RESUMO
CONTEXT: No universal waist circumference (WC) percentile cutoffs used have been proposed for screening central obesity in children and adolescents. OBJECTIVE: To develop international WC percentile cutoffs for children and adolescents with normal weight based on data from 8 countries in different global regions and to examine the relation with cardiovascular risk. DESIGN AND SETTING: We used pooled data on WC in 113,453 children and adolescents (males 50.2%) aged 4 to 20 years from 8 countries in different regions (Bulgaria, China, Iran, Korea, Malaysia, Poland, Seychelles, and Switzerland). We calculated WC percentile cutoffs in samples including or excluding children with obesity, overweight, or underweight. WC percentiles were generated using the general additive model for location, scale, and shape (GAMLSS). We also estimated the predictive power of the WC 90th percentile cutoffs to predict cardiovascular risk using receiver operator characteristics curve analysis based on data from 3 countries that had available data (China, Iran, and Korea). We also examined which WC percentiles linked with WC cutoffs for central obesity in adults (at age of 18 years). MAIN OUTCOME MEASURE: WC measured based on recommendation by the World Health Organization. RESULTS: We validated the performance of the age- and sex-specific 90th percentile WC cutoffs calculated in children and adolescents (6-18 years of age) with normal weight (excluding youth with obesity, overweight, or underweight) by linking the percentile with cardiovascular risk (area under the curve [AUC]: 0.69 for boys; 0.63 for girls). In addition, WC percentile among normal weight children linked relatively well with established WC cutoffs for central obesity in adults (eg, AUC in US adolescents: 0.71 for boys; 0.68 for girls). CONCLUSION: The international WC cutoffs developed in this study could be useful to screen central obesity in children and adolescents aged 6 to 18 years and allow direct comparison of WC distributions between populations and over time.
Assuntos
Estatura , Índice de Massa Corporal , Obesidade Abdominal/epidemiologia , Sobrepeso/epidemiologia , Obesidade Infantil/epidemiologia , Circunferência da Cintura , Adolescente , Adulto , Área Sob a Curva , Criança , Pré-Escolar , Estudos Transversais , Feminino , Seguimentos , Humanos , Irã (Geográfico)/epidemiologia , Malásia/epidemiologia , Masculino , Obesidade Abdominal/fisiopatologia , Sobrepeso/fisiopatologia , Obesidade Infantil/fisiopatologia , Polônia/epidemiologia , Prognóstico , Fatores Sexuais , Suíça/epidemiologia , Adulto JovemRESUMO
Most of inborn errors of metabolism (IEMs) and rare endocrine-metabolic diseases (REMD) are rare diseases. According to the European Commission on Public Health, a rare disease is defined, based on its prevalence, as one affecting one in 2000 people. Many IEMs affect body stature, cause craniofacial abnormalities, and disturb the developmental process. Therefore, body proportion, dysmorphic characteristics, and morphological parameters must be assessed and closely monitored. This can be achieved only with the help of an anthropologist who has adequate tools. This is why the role of an anthropologist in collaboration with the physician in the diagnostic process is not to be underestimated. Clinical anthropologists contribute to assessing physical development and improve our understanding of the natural history of rare metabolic diseases. This paper presents anthropometric techniques and methods, such as analysis of demographic data, anthropometric parameters at birth, percentile charts, growth patterns, bioimpedance, somatometric profiles, craniofacial profiles, body proportion indices, and mathematical models of growth curves used in certain rare diseases. Contemporary anthropological methods play an important role in the diagnostic process of rare genetic diseases.
Assuntos
Antropologia/métodos , Erros Inatos do Metabolismo/diagnóstico , Doenças Raras/diagnóstico , HumanosRESUMO
Mucopolysaccharidosis type IVA, also known as Morquio (Morquio-Brailsford) syndrome results from accumulation of keratan sulfate (KS) and chondroitin-6-sulfate (C6S), whereas the primary cause is mutations in the gene encoding galactosamine (N-acetyl)-6-sulfatase (GALNS). Phenotypically it seems to be a well-defined condition, with two main clinical forms: mild (attenuated) and severe, which are determined based on a combination of symptoms, i.e., enzymatic activity of GALNS, age of onset, and symptom severity. Nevertheless, the natural history of MPSIVA in relation to specific anthropometric parameters (growth, head circumference, body proportions, and face phenotype) is not precisely characterized. The aim of our work was to analyze the aforementioned anthropometric parameters, including correlation to molecular data (causative GALNS mutations).
Assuntos
Sulfatos de Condroitina/genética , Condroitina Sulfatases/genética , Sulfato de Queratano/genética , Mucopolissacaridose IV/genética , Adolescente , Adulto , Antropometria/métodos , Criança , Pré-Escolar , Sulfatos de Condroitina/metabolismo , Europa (Continente) , Feminino , Genótipo , Humanos , Lactente , Sulfato de Queratano/metabolismo , Masculino , Mucopolissacaridose IV/fisiopatologia , Mutação , Fenótipo , Adulto JovemRESUMO
During progressive myopathy, the space of atrophic muscle tissue is gradually filled by fatty tissue. The proportion of these two tissue types relative to body mass provides an indication of the extent of muscle tissue destruction, i.e., the progression and severity of the disease.In this study we use Pompe disease as an example to report the new possibility of using bioimpedance analysis (BIA) to assess the relative proportion of fatty and muscle tissue in diseases associated with muscle atrophy, thus enabling the assessment of disease progression and the effectiveness of treatment. Results from BIA analysis were compared with magnetic resonance images.The results of muscle magnetic resonance images and BIA analysis were similar, which suggests that BIA may provide valuable diagnostic guidance for the assessment of the progression of the disorder.
RESUMO
BACKGROUND: The objective of the study was to compare mean values for birth body length and weight between patients with mucopolysaccharidosis (MPS) and the general population. METHODS: A retrospective analysis of birth anthropometric data was performed for patients (n = 103) with MPS I, II, and VI. Two-tailed t tests were used to compare mean values for body length and weight at birth between patients with MPS and the general population. RESULTS: Mean values for birth body length and weight for all studied groups were greater than in the general population. For body length the differences were statistically significant. When considered individually, 53% of patients were large for gestational age (LGA) and 30% were macrosomic. The highest percentage of LGA was observed in MPS II males and MPS VI females (55% and 56%, respectively), while the highest percentage of macrosomia was observed in MPS VI males (36%). CONCLUSION: At the time of birth, MPS patients were larger than those in the general population. High birth weight and/or LGA can be suggestive of MPS disease and should raise suspicion aiding early disease recognition.