A Clinical Multicenter Study of Orofacial Features in 26 Brazilian Patients with Different Types of Mucopolysaccharidosis
Erlane Marques RibeiroCristiane Sá Roriz FontelesAdriana Bezerra FreitasKarla Shangela da Silva AlvesAndré Jalles MonteiroCarlos Antônio Bruno da Silva
17
Citation
30
Reference
10
Related Paper
Citation Trend
Abstract:
Purpose This study aimed to describe the orofacial features of 26 unrelated Brazilian patients with mucopolysaccharidosis and to verify any possible associations between these findings and specific types of mucopolysaccharidosis. Methods Patients were diagnosed with mucopolysaccharidosis and clinically evaluated. Following consent, a clinical assessment form was completed. Facial and intraoral examination was performed by evaluating facial pattern, malocclusions, dental caries, and tooth identification. Results Midface deficiency, increased lower facial third, anterior open bite, convex profile, macroglossia, gingival enlargement, and spaced arches were the most frequently observed features. These findings did not allow a differential diagnosis among the different types of mucopolysaccharidosis, except for pitting enamel, which significantly associated with mucopolysaccharidosis IVA ( P < .001). Open bite was associated with mucopolysaccharidosis types I, II, III, and VI; however, only one patient with mucopolysaccharidosis IVA expressed this feature ( P = .043). Conclusions Our results suggest that pitted enamel in patients with mucopolysaccharidosis is most likely a feature of mucopolysaccharidosis type IVA; whereas, open bite is rarely observed in these patients. Orofacial features in mucopolysaccharidosis may help pediatric dentists recognize this disorder and minimize the delay between the initial signs/symptoms and diagnosis of the disease. Future studies should focus on the longitudinal manifestations, expression, and severity of mucopolysaccharidosis-associated orofacial anomalies.Keywords:
Mucopolysaccharidosis
Mucopolysaccharidosis I
Macroglossia
Mucopolysaccharidosis type I
Cite
Abstract Purpose Current newborn screening (NBS) for mucopolysaccharidosis type I (MPSI) has very high false positive rates and low positive predictive values (PPVs). To improve the accuracy of presymptomatic prediction for MPSI, we propose an NBS tool based on known biomarkers, alpha‐L‐iduronidase enzyme activity (IDUA) and level of the glycosaminoglycan (GAG) heparan sulfate (HS). Methods We developed the NBS tool using measures from dried blood spots (DBS) of 5000 normal newborns from Gifu Prefecture, Japan. The tool's predictive accuracy was tested on the newborn DBS from these infants and from seven patients who were known to have early‐onset MPSI (Hurler's syndrome). Bivariate analyses of the standardized natural logarithms of IDUA and HS levels were employed to develop the tool. Results Every case of early‐onset MPSI was predicted correctly by the tool. No normal newborn was incorrectly identified as having early‐onset MPSI, whereas 12 normal newborns were so incorrectly identified by the Gifu NBS protocol. The PPV was estimated to be 99.9%. Conclusions Bivariate analysis of IDUA with HS in newborn DBS can accurately predict early MPSI symptoms, control false positive rates, and enhance presymptomatic treatment. This bivariate analysis‐based approach, which was developed for Krabbe disease, can be extended to additional screened disorders.
Mucopolysaccharidosis type I
Mucopolysaccharidosis I
Mucopolysaccharidosis
Hurler syndrome
Dried blood spot
Dried blood
Lysosomal storage disease
Cite
Citations (11)
Mucopolysaccharidosis type I (MPS I) is the prototype lysosomal storage disease. It is characterized by a deficiency of the enzyme a-L-iduronidase, resulting in the accumulation of glycosaminoglycans in different tissues and organs with varying severity and three clinical presentations according to severiry. We report the case of a 19-year-old male patient with a confirmed diagnosis of MPS I and enzymatic treatment with a favorable clinical response. The objective of this report is to describe the clinical picture, course and treatment of MPS I, and the role of the internist in disease monitoring and management of complications.
Mucopolysaccharidosis I
Hurler syndrome
Mucopolysaccharidosis type I
Mucopolysaccharidosis
Lysosomal storage disease
Cite
Citations (0)
Summary Children with any of the mucopolysaccharidoses are at a high risk of developing significant morbidity and mortality when a general anaesthetic is administered. This case report describes the use of a caudal epidural technique for the repair of bilateral inguinal herniae in a 10‐month‐old infant with Hurler syndrome (mucopolysaccharidosis type I).
Hurler syndrome
Mucopolysaccharidosis
Mucopolysaccharidosis type I
Mucopolysaccharidosis I
Hunter syndrome
Cite
Citations (2)
Hurler syndrome (HS; mucopolysaccharidosis type I) is a lysosomal storage disorder caused by a deficiency of iduronidase, with resultant accumulation of glycosaminoglycans in viscera and brain. Hematopoietic cell transplantation (HCT) has been shown to be a life-saving measure for children with HS. To decrease the toxicity of HCT we have offered intravenous iduronidase enzyme replacement therapy (IV ERT) before and after HCT. Twelve children with HS at a median age of 1.5 years at the time of myeloablative HCT were eligible. Iduronidase (0.58 mg/kg/dose) was administered intravenously in 11–14 weekly doses before HCT and 8 weekly doses after HCT. The infusions were well tolerated. All patients developed antibodies to iduronidase, but on day 100 had >90% donor hematopoiesis, suggesting that ERT prior to HCT is unlikely to alter donor engraftment. All are alive and well, with a median follow-up of more than 1 year after HCT. Patients with HS, however, also develop central nervous system (CNS) pathology, and IV-administered iduronidase has been shown ineffective in crossing the blood-brain barrier. Encouraged by the results of intrathecal ERT (IT ERT) studies in the animal model of HS, we reasoned that clinical investigations incorporating IT ERT, IV ERT, and HCT may provide increased benefit to HS patients. To date, we have enrolled 3 patients with HS on this IT ERT study. The dose administered is 0.05 mg/kg iduronidase in 3 mL of Elliot's B solution. Four doses of drug are administered: the first beginning at the time of IV ERT, the second just prior to transplantation, the third 100 days post HCT, and the last 180 days post transplantation. This timing was chosen to deliver enzyme to the brain until it is anticipated that donor microglial cells are present in sufficient numbers to deliver enzyme to the CNS. At present, one patient has received all doses, while the others continue on study. The 2 patients who were transplanted are alive and fully engrafted at day 100. Magnetic resonance imaging and cerebrospinal fluid analysis at the time of IT ERT showed no evidence of brain inflammation. Our data thus demonstrate that multimodal cellular and enzyme therapy in HS is feasible. Importantly, it affirms the safety of IT ERT, IV ERT, and HCT combination therapy, and provides a rationale for application of this strategy to additional HS patients in order to assess fully its impact on long-term neuropsychological function of HS patients.
Mucopolysaccharidosis I
Hurler syndrome
Mucopolysaccharidosis type I
Mucopolysaccharidosis
Hunter syndrome
Lysosomal storage disease
Mucopolysaccharidosis type II
Cite
Citations (2)
Mucopolysaccharidosis I (MPS I) is a rare inherited disorder that belongs to a group of clinically progressive disorders and is caused by the deficiency of the lysosomal enzyme, α(1)-iduronidase. MPS I has been recently classified into a severe (Hurler syndrome) and an attenuated type (Hurler-Scheie and Scheie syndromes). The purpose of this article was to describe a rare case of MPS type I, attenuated type (Hurler-Scheie) affecting a 15-year-old Indian child.
Mucopolysaccharidosis type I
Hurler syndrome
Mucopolysaccharidosis I
Mucopolysaccharidosis
Lysosomal Storage Disorders
Cite
Citations (14)
Mucopolysaccharidosis I (McKusick 25280, Hurler syndrome, Scheie syndrome) is caused by a deficiency in the lysosomal hydrolase, alpha-L-iduronidase (EC 3.2.1.76) and results in a failure to degrade the glycosaminoglycans, dermatan sulfate and heparan sulfate. Mucopolysaccharidosis I patients present within a spectrum of clinical phenotypes, where Hurler and Scheie syndromes represent the two extremes. In the 80 or more years since the discovery of mucopolysaccharidosis I, the molecular defect has been defined, the alpha-L-iduronidase protein purified and characterised, the alpha-L-iduronidase (IDUA) gene cloned, molecular genetic studies performed and expression systems developed. These advances have allowed the development of alpha-L-iduronidase enzyme replacement therapy as a treatment strategy for mucopolysaccharidosis I patients. Using animal models of mucopolysaccharidosis I, the efficacy of alpha-L-iduronidase replacement therapy has been evaluated and justified the initiation of human clinical trials in mucopolysaccharidosis I patients. Phase I/II and Phase III clinical trials have recently been conducted and demonstrated that this therapy is effective in treating patients with the attenuated forms of mucopolysaccharidosis I (that is, little or no neuronal involvement). Further development of this technology is required to effectively treat the problem sites of neuronal and skeletal pathology, present in severe Hurler syndrome patients.
Hurler syndrome
Mucopolysaccharidosis I
Mucopolysaccharidosis type I
Mucopolysaccharidosis
Lysosomal storage disease
Cite
Citations (28)
Hurler syndrome
Mucopolysaccharidosis
Mucopolysaccharidosis I
Mucopolysaccharidosis type I
Presentation (obstetrics)
Cite
Citations (17)
The mucopolysaccharidoses are a group of lysosomal storage diseases caused by a deficiency of enzymes that degrade glycosaminoglycans.1 Mucopolysaccharidosis type I, an autosomal recessive disorder caused by a deficiency of the enzyme α-L-iduronidase, is characterized by multisystemic clinical disease. The α-L-iduronidase deficiency leads to the progressive accumulation of glycosaminoglycans, resulting in tissue and organ dysfunction. A wide range of clinical presentations, with variations in the severity of symptoms and the extent of central nervous system involvement, is observed in patients with iduronidase deficiency.In 1919, a German pediatrician named Gertrud Hurler provided the first description of mucopolysaccharidosis type I. Characteristics . . .
Mucopolysaccharidosis I
Mucopolysaccharidosis
Mucopolysaccharidosis type I
Hurler syndrome
Lysosomal storage disease
Enzyme deficiency
Cite
Citations (88)
Rare diseases are often un- or misdiagnosed for extended periods, resulting in a long diagnostic delay that may significantly add to the burden of the disease. An early diagnosis is particularly essential if a disease-modifying treatment is available. The purpose of this study was to assess the extent of the diagnostic delay in the two ultra-rare diseases, i.e., mucopolysaccharidosis I (MPS I) and III (MPS III), both of which are lysosomal storage disorders with different phenotypic severities (MPS 1 is characterized by the severe Hurler and the more attenuated non-Hurler phenotypes, MPS III is characterized by the severe rapidly progressing (RP) phenotype and more attenuated slowly progressing (SP) phenotype). We investigated whether the diagnostic delay changed over the previous decades.The diagnostic delay, which is defined as the time between the first visit to a medical doctor for disease-related symptoms and the final diagnosis, was assessed using telephone interviews with patients diagnosed between 1988 and 2017 and/or their parents or legal guardian(s). In addition, the medical charts were reviewed. For MPS I (n = 29), the median diagnostic delay was 8 months (range 1-24 months) for Hurler patients and 28 months (range 2-147 months) for non-Hurler patients. For MPS III (n = 46), the median diagnostic delay was 33 months (range 1-365 months). No difference was observed between the RP and SP phenotypic groups. Comparing the diagnostic delay over time using 5-year time intervals, no reduction in the diagnostic delay was observed for MPS I or MPS III.In the Netherlands, the time to diagnosis for patients with MPS I and MPS III has not changed between 1988 and 2017, and an extensive delay still exists between the first visit to a medical doctor for disease-related symptoms and the final diagnosis. The numerous campaigns launched to increase awareness, leading to earlier diagnosis of these rare disorders, particularly of MPS I, have failed to achieve their goal. Robust selected screening protocols embedded in national guidelines and newborn screening for disorders that meet the criteria for population screening may be the only effective approaches for reducing the diagnostic delay.
Mucopolysaccharidosis type I
Mucopolysaccharidosis
Mucopolysaccharidosis I
Lysosomal Storage Disorders
Lysosomal storage disease
Hurler syndrome
Neuronal ceroid lipofuscinosis
Mucopolysaccharidosis type II
Rare disease
Cite
Citations (55)