RESUMEN
INTRODUCTION: Current literature lacks consensus on initial assessments and routine follow-up care of patients with alpha-mannosidosis (AM). A Delphi panel was conducted to generate and validate recommendations on best practices for initial assessment, routine follow-up care, and integrated care coordination of patients with AM. METHODS: A modified Delphi method involving 3 rounds of online surveys was used. An independent administrator and 2 nonvoting physician co-chairs managed survey development, anonymous data collection, and analysis. A multidisciplinary panel comprising 20 physicians from 12 countries responded to 57 open-ended questions in the first survey. Round 2 consisted of 11 ranking questions and 44 voting statements. In round 3, panelists voted to validate 60 consensus statements. The panel response rate was ≥95% in all 3 rounds. Panelists used 5-point Likert scales to indicate importance (score of ≥3) or agreement (score of ≥4). Consensus was defined a priori as ≥75% agreement with ≥75% of panelists voting. RESULTS: Consensus was reached on 60 statements, encompassing 3 key areas: initial assessments, routine follow-up care, and treatment-related follow-up. The panel agreed on the type and frequency of assessments related to genetic testing, baseline evaluations, quality of life, biochemical measures, affected body systems, treatment received, and integrated care coordination in patients with AM. Forty-nine statements reached 90% to 100% consensus, 8 statements reached 80% to 85% consensus, and 1 statement reached 75% consensus. Two statements each reached consensus on 15 baseline assessments to be conducted at the initial follow-up visit after diagnosis in pediatric and adult patients. CONCLUSION: This is the first Delphi study providing internationally applicable, best-practice recommendations for monitoring patients with AM that may improve their care and well-being.
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Consenso , Técnica Delphi , alfa-Manosidosis , Humanos , alfa-Manosidosis/terapia , alfa-Manosidosis/diagnóstico , Encuestas y Cuestionarios , Prestación Integrada de Atención de Salud/normasRESUMEN
Alpha-mannosidosis is an ultra-rare lysosomal disease that is caused by variants of the MAN2B1 gene on chromosome 19p13. These variants result in faulty or absent alpha-mannosidase in lysosomes, which leads to intracellular accumulation of mannose-containing oligosaccharides. Diagnosis of alpha-mannosidosis is often delayed, in part because of the rarity of the disease, its gradual onset and heterogeneity of presentation, but also because of the similarity of many signs and symptoms of the disease to those of other lysosomal diseases. Treatment of alpha-mannosidosis was previously limited to hematopoietic stem cell transplantation, but outcomes are variable and not all patients are eligible or have a suitable donor. Recently, an enzyme replacement therapy, recombinant human alpha-mannosidase (velmanase alfa), was approved for the treatment of non-neurological manifestations in adult and pediatric patients with alpha-mannosidosis. Treatment with velmanase alfa reduces serum levels of oligosaccharides, increases levels of immunoglobulin G, and improves patients' functional capacity and quality of life, although it is not effective for the neurologic phenotype because it does not cross the blood-brain barrier. Since the effects of velmanase alfa are more marked in children than adults, early diagnosis to allow early initiation of treatment has become more important. To support this, patient, parent/caregiver, and clinician awareness and education is imperative. A number of approaches can be taken to meet this goal, such as the development of disease registries, validated diagnostic algorithms, and screening tools, improved under-/post-graduate clinician education, easily accessible and reliable information for patients/families (such as that made available on the internet), and the formation of patient advocacy groups. Such approaches may raise awareness of alpha-mannosidosis, reduce the diagnostic delay and thus improve the lives of those affected.
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Diagnóstico Tardío , Terapia de Reemplazo Enzimático , alfa-Manosidasa , alfa-Manosidosis , Humanos , alfa-Manosidosis/diagnóstico , alfa-Manosidosis/genética , alfa-Manosidasa/genética , Enfermedades Raras/diagnóstico , Enfermedades Raras/genéticaRESUMEN
Alpha-mannosidosis is a rare autosomal recessive lysosomal storage disorder caused by biallelic mutations in the MAN2B1 gene and characterized by a wide clinical heterogeneity. Diagnosis for this multisystemic disorder is confirmed by the presence of either a deficiency in the lysosomal enzyme acid alpha-mannosidase or biallelic mutations in the MAN2B1 gene. This diagnosis confirmation is crucial for both clinical management and genetic counseling purposes. Here we describe a late diagnosis of alpha-mannosidosis in a patient presenting with syndromic intellectual disability, and a rare retinopathy, where reverse phenotyping played a pivotal role in interpreting the exome sequencing result. While a first missense variant was classified as a variant of uncertain significance, the phenotype-guided analysis helped us detect and interpret an in-trans apparent alu-element insertion, which appeared to be a copy number variant (CNV) not identified by the CNV caller. A biochemical analysis showing abnormal excretion of urinary mannosyloligosaccharide and an enzyme assay permitted the re-classification of the missense variant to likely pathogenic, establishing the diagnosis of alpha-mannosidosis. This work emphasizes the importance of reverse phenotyping in the context of exome sequencing.
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alfa-Manosidosis , Humanos , alfa-Manosidosis/diagnóstico , alfa-Manosidosis/genética , Variaciones en el Número de Copia de ADN/genética , alfa-Manosidasa/genética , Mutación Missense/genética , FenotipoRESUMEN
Alpha-mannosidosis (MIM #248500) is an ultra-rare autosomal recessive lysosomal storage disease with multi-system involvement and a wide phenotypic spectrum. Information on long-term outcomes remains poor. We present the long-term outcomes (median, 19 years) of nine patients with alpha-mannosidosis, three females and six males, followed at a single center. The findings of the nine patients were collected from medical records and reported as mean ± SD or median, and range. The age of onset of the first symptoms ranged from 0-1 to 10 years. The diagnostic delay ranged from 2 to 22 years (median= 11 years). Coarse face, hearing, heart valves, joints, gait, language, dysarthria, psychiatric symptoms, I.Q., MRI, walking disabilities, orthopedic disturbances and surgeries showed a slow worsening over the decades. Our patients showed a slowly worsening progressive outcome over the decades. Psychiatric symptoms were present in 100% of our population and improved with the appropriate pharmacological intervention. This aspect requires attention when following up on these patients. Our description of the long-term evolution of alpha-mannosidosis patients may provide basic knowledge for understanding the effects of specific treatments.
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Trastornos Mentales , alfa-Manosidosis , Masculino , Femenino , Humanos , Recién Nacido , Lactante , Preescolar , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , alfa-Manosidosis/diagnóstico , Diagnóstico Tardío , Patrón de Herencia , Italia/epidemiologíaRESUMEN
OBJECTIVES: Alpha-mannosidosis is a rare genetic lysosomal storage condition leading to the systemic buildup of oligomannoside. Clinical presentation and associated conditions, as well as the full extent of histopathologic changes associated with this disease process, are not fully understood. CASE PRESENTATION: We present the case of an 8-year-1-month old patient with persistent anemia and who was initially diagnosed with Celiac disease before ultimately being diagnosed with alpha-mannosidosis. As part of his diagnostic work-up, duodenal and bone marrow biopsies were examined by pathology. Duodenal biopsies showed foamy plasma cells expanding the lamina propria which triggered a workup for a genetic storage disease; features suggestive of Celiac disease which resolved on gluten-free diet were also noted by pathology. Bone marrow analysis via electron microscopy showed cytoplasmic granules and inclusions in multiple immune cell lines. CONCLUSIONS: Alpha-mannosidosis can occur with Celiac disease and milder forms may only be suspected from incidental pathology findings. The ultrastructural bone marrow findings from this case, the first to be reported from human, show numerous disease-associated changes in multiple immune cell lines whose contribution to disease-associated immunodeficiency is unclear.
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Enfermedad Celíaca , Enfermedades por Almacenamiento Lisosomal , alfa-Manosidosis , Humanos , Lactante , alfa-Manosidosis/diagnóstico , alfa-Manosidosis/complicaciones , alfa-Manosidosis/genética , Microscopía , Enfermedad Celíaca/complicaciones , Enfermedades por Almacenamiento Lisosomal/diagnósticoRESUMEN
We describe the first case of bridge therapy in alpha-mannosidosis (AM) in an infant diagnosed at only 5 months of life who underwent enzyme replacement therapy (ERT) in the pre- and peri-transplant phases. Eight ERT infusions were administered before hematopoietic stem cell transplantation (HSCT) and continued for additional 90 days until complete engraftment. The clinical and laboratory data after 3 years post-HSCT show that the early combined intervention may reduce the disease progression and the urine and plasma content of mannosyl-oligosaccharides (OS) monitored by liquid chromatography tandem mass spectrometry (LC-MS/MS). This report highlights that early diagnosis and prompt initiation of such treatments in AM are the best chance to minimize the progression of symptoms.
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Trasplante de Células Madre Hematopoyéticas , alfa-Manosidosis , Lactante , Humanos , alfa-Manosidosis/diagnóstico , alfa-Manosidosis/terapia , Terapia de Reemplazo Enzimático/métodos , Cromatografía Liquida , Espectrometría de Masas en TándemRESUMEN
OBJECTIVE: Despite profound neurological symptomatology there are only few MRI studies focused on the brain abnormalities in alpha-mannosidosis (AM). Our aim was to characterize brain MRI findings in a large cohort of AM patients along with clinical manifestations. METHODS: Twenty-two brain MRIs acquired in 13 untreated AM patients (8 M/5F; median age 17 years) were independently assessed by three experienced readers and compared to 16 controls. RESULTS: Focal and/or diffuse hyperintense signals in the cerebral white matter were present in most (85%) patients. Cerebellar atrophy was common (62%), present from the age of 5 years. Progression was observed in two out of 6 patients with follow-up scans. Cortical atrophy (62%) and corpus callosum thinning (23%) were already present in a 13-month-old child. The presence of low T2 signal intensity in basal ganglia and thalami was excluded by the normalized signal intensity profiling. The enlargement of perivascular spaces in white matter (38%), widening of perioptic CSF spaces (62%), and enlargement of cisterna magna (85%) were also observed. Diploic space thickening (100%), mucosal thickening (69%) and sinus hypoplasia (54%) were the most frequent non-CNS abnormalities. CONCLUSION: White matter changes and cerebellar atrophy are proposed to be the characteristic brain MRI features of AM. The previously reported decreased T2 signal intensity in basal ganglia and thalami was not detected in this quantitative study. Rather, this relative MR appearance seems to be related to the diffuse high T2 signal in the adjacent white matter and not the gray matter iron deposition that has been hypothesized.
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Atrofia/diagnóstico , Cerebelo/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagen , alfa-Manosidosis/diagnóstico , Adolescente , Adulto , Atrofia/diagnóstico por imagen , Atrofia/patología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Cerebelo/patología , Niño , Preescolar , Femenino , Humanos , Lactante , Imagen por Resonancia Magnética/métodos , Masculino , Malformaciones del Sistema Nervioso/diagnóstico , Malformaciones del Sistema Nervioso/diagnóstico por imagen , Malformaciones del Sistema Nervioso/patología , Neuroimagen/métodos , Sustancia Blanca/patología , Adulto Joven , alfa-Manosidosis/diagnóstico por imagen , alfa-Manosidosis/patologíaAsunto(s)
Distrofias Retinianas/diagnóstico , alfa-Manosidosis/diagnóstico , alfa-Manosidosis/genética , Adulto , Alelos , Preescolar , Consanguinidad , Análisis Mutacional de ADN , Facies , Femenino , Angiografía con Fluoresceína , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Masculino , Mutación , Linaje , Fenotipo , Distrofias Retinianas/etiología , Evaluación de Síntomas , alfa-Manosidasa/genética , alfa-Manosidasa/metabolismo , alfa-Manosidosis/complicacionesRESUMEN
Individuals affected by alpha-Mannosidosis suffer from similar clinical symptoms such as respiratory infections, skeletal changes as patients with mucopolysaccharidoses (MPS). α-Mannosidosis is considered as an ultra-rare disorders and also diagnostic testing is often limited. With the availability of novel therapies and easy-to-access diagnostic tests (e.g. Tandem mass spectrometry) using dried blood spots for both enzymatic and genetic testing, the chance for the development of a better understanding of disease and awareness may be triggered. In a pilot study, we have investigated 1010 residual dried blood spot samples from individuals suspicious to MPS. In these study cohort, 158/1010 individuals were genetically confirmed for MPS. Additional biochemical and genetic confirmatory testing for α-mannosidases revealed four individuals with a final diagnosis of α-mannosidosis. This unexpected high number of individuals with α-mannosidosis demonstrated the urgent need of taking this rare disorder in clinical and diagnostic consideration particularly in patients suspicious to MPS.
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Mutación , alfa-Manosidasa/sangre , alfa-Manosidasa/genética , alfa-Manosidosis/diagnóstico , Pruebas con Sangre Seca , Humanos , Proyectos Piloto , alfa-Manosidosis/enzimología , alfa-Manosidosis/genéticaRESUMEN
Alpha-mannosidosis (OMIM 248500) is a rare lysosomal storage disorder caused by a deficiency of the enzyme alpha-mannosidase. Recently, enzyme replacement therapy was approved in the European Union for the treatment of alpha-mannosidosis, but evaluation regarding long-term efficacy and safety is hard to assess due to missing quantitative natural history data, in particular survival. We performed a quantitative analysis of published cases (N = 111) with alpha-mannosidosis. Main outcome measures were age of disease onset, diagnostic delay and survival (overall and by subgroup exploration). Residual alpha-mannosidase activity and age of onset were explored as potential predictors of survival. STROBE criteria were respected. Median age of onset was 12 months. Median diagnostic delay was 6 years. At the age of 41 years 72.3% of patients were alive (N = 111). Residual alpha-mannosidase activity (N = 34) predicted survival: Patients with a residual alpha-mannosidase activity below or equal to 4.5% of normal in fibroblasts had a median survival of 3.5 years, whereas patients with alpha-mannosidase activity above this threshold all survived during the observation period reported. Patients with age of onset above 7 years survived significantly longer than patients with age of onset below or equal to 7 years. Patient distribution was panethnic with hotspots in the United States and Germany. We defined age of onset, diagnostic delay, and survival characteristics in a global cohort of 111 patients with alpha-mannosidosis by retrospective quantitative natural history modeling. These data expand the quantitative understanding of the clinical phenotype.
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alfa-Manosidosis/diagnóstico , alfa-Manosidosis/mortalidad , Adolescente , Adulto , Edad de Inicio , Biomarcadores , Niño , Preescolar , Estudios Transversales , Diagnóstico Tardío , Terapia de Reemplazo Enzimático , Femenino , Humanos , Lactante , Masculino , Fenotipo , Estudios Retrospectivos , Análisis de Supervivencia , Adulto Joven , alfa-Manosidosis/tratamiento farmacológicoRESUMEN
Multiplex tandem mass spectrometry (MS/MS)-based enzyme activity assays for newborn screening (NBS) and diagnosis of lysosomal storage diseases (LSDs) in newborns, using dried blood spots (DBS) on newborn screening cards, have garnered much attention due to its sensitivity, high precision, and the capability to screen for an unprecedented number of diseases in a single assay. Herein we report the development of MS/MS-based enzyme assays for the diagnosis of α-mannosidosis and fucosidosis. These new protocols are able to distinguish untreated patients from random newborns, carriers and a post-bone marrow transplant patient. We have successfully multiplexed the α-mannosidosis assay with a multiplex MS/MS assay for the screening and diagnosis of other LSDs, namely Fabry, Pompe, MPS I, Gaucher, Niemann-Pick-A/B, and Krabbe diseases. Additionally, we also multiplexed the fucosidosis NBS assay with a 5-plex assay that tests for MPS-II, MPS-IIIB, MPS-IVA, MPS-VI and MPS-VII.
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Fucosidosis/diagnóstico , Enfermedades por Almacenamiento Lisosomal/diagnóstico , Tamizaje Neonatal/métodos , Espectrometría de Masas en Tándem/métodos , alfa-Manosidosis/diagnóstico , Pruebas de Enzimas , Humanos , Recién NacidoRESUMEN
Alpha-mannosidosis is an ultra-rare progressive lysosomal storage disorder caused by deficiency of alpha-mannosidase. Timely diagnosis of the disease has the potential to influence patient outcomes as preventive therapies can be initiated at an early stage. However, no internationally-recognised algorithm is currently available for the diagnosis of the disease. With the aim of developing a diagnostic algorithm for alpha-mannosidosis an international panel of experts met to reach a consensus by applying the nominal group technique. Two proposals were developed for diagnostic algorithms of alpha-mannosidosis, one for patients ≤10â¯years of age and one for those >10â¯years of age. In younger patients, hearing impairment and/or speech delay are the cardinal symptoms that should prompt the clinician to look for additional symptoms that may provide further diagnostic clues. Older patients have different clinical presentations, and the presence of mental retardation and motor impairment progression and/or psychiatric manifestations should prompt the clinician to assess for other symptoms. In both younger and older patients, either additional metabolic monitoring or referral for testing is warranted upon suspicion of disease. Oligosaccharides in urine (historically performed) or serum were considered as an initial screening procedure, while enzymatic activity may also be considered as first choice in some centres. Molecular testing should be performed as a final confirmatory step. The developed algorithms can easily be applied in a variety of settings, and may help to favour early diagnosis of alpha mannosidosis and treatment.
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Algoritmos , Internacionalidad , alfa-Manosidosis/diagnóstico , Adolescente , Adulto , Factores de Edad , Niño , Preescolar , Consenso , Progresión de la Enfermedad , Humanos , Persona de Mediana Edad , Adulto JovenRESUMEN
There are numerous poisonous plants that can induce intralysosomal accumulation of glycoproteins and neurologic syndromes. Here we describe for the first time, a disease caused by ingesting Sida rodrigoi Monteiro in goats in North-western Argentina. The animals showed weight loss, indifference to the environment, unsteady gait and ataxia. Histopathologic studies showed vacuolization in cells of various organs, mainly in the CNS. The material deposited in the cells was positive for LCA (Lens culinaris agglutinin), WGA (Triticum vulgaris agglutinin), sWGA (succinyl-Triticum vulgaris agglutinin) and Con-A (Concanavalia ensiformis agglutinin) lectins. Finally, toxic levels of swansonine were identified in the plant. The present investigation allowed to recognize S. rodrigoi Monteiro poisoning as a plant induced α-mannosidosis.
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Enfermedades de las Cabras/diagnóstico , Malvaceae/química , Intoxicación por Plantas/veterinaria , Swainsonina/toxicidad , alfa-Manosidosis/veterinaria , Alimentación Animal/análisis , Animales , Argentina , Ataxia/diagnóstico , Ataxia/etiología , Ataxia/veterinaria , Sistema Nervioso Central/fisiopatología , Dieta/veterinaria , Enfermedades de las Cabras/etiología , Cabras , Lectinas de Plantas/análisis , Intoxicación por Plantas/diagnóstico , Intoxicación por Plantas/etiología , Plantas Tóxicas/química , alfa-Manosidosis/diagnóstico , alfa-Manosidosis/etiologíaRESUMEN
α-Mannosidosis (AMD) is an autosomal recessively inherited lysosomal storage disorder affecting brain function and structure. We performed ex vivo and in vivo diffusion tensor imaging (DTI) on the brains of AMD-affected cats to assess gray and white matter abnormalities. A multi-atlas approach was used to generate a brain template to process the ex vivo DTI data. The probabilistic label method was used to measure fractional anisotropy (FA), mean diffusivity, axial diffusivity, and radial diffusivity values from gray and white matter regions from ex vivo DTI. Regional analysis from various regions of the gray matter (frontal cortex, cingulate gyrus, caudate nucleus, hippocampus, thalamus, and occipital cortex), and white matter (corpus callosum, corticospinal tract, cerebral peduncle, external and internal capsule) was also performed on both ex vivo and in vivo DTI. Ex vivo DTI revealed significantly reduced FA from both gray and white matter regions in AMD-affected cats compared to controls. Significantly reduced FA was also observed from in vivo DTI of AMD-affected cats compared to controls, with lower FA values observed in all white matter regions. We also observed significantly increased axial and radial diffusivity values in various gray and white matter regions in AMD cats from both ex vivo and in vivo DTI data. Imaging findings were correlated with histopathologic analyses suggesting that DTI studies can further aid in the characterization of AMD by assessing the microstructural abnormalities in both white and gray matter.
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Imagen de Difusión Tensora/métodos , Sustancia Gris/metabolismo , Sustancia Gris/patología , Sustancia Blanca/metabolismo , Sustancia Blanca/patología , alfa-Manosidosis/metabolismo , Animales , Animales Modificados Genéticamente , Gatos , alfa-Manosidosis/diagnósticoRESUMEN
α-Mannosidosis is an autosomal recessive lysosomal storage disorder caused by mutations in the MAN2B1 gene, encoding lysosomal α-mannosidase. The disorder is characterized by a range of clinical phenotypes of which the major manifestations are mental impairment, hearing impairment, skeletal changes, and immunodeficiency. Here, we report an α-mannosidosis mutation database, amamutdb.no, which has been constructed as a publicly accessible online resource for recording and analyzing MAN2B1 variants (http://amamutdb.no). Our aim has been to offer structured and relational information on MAN2B1 mutations and genotypes along with associated clinical phenotypes. Classifying missense mutations, as pathogenic or benign, is a challenge. Therefore, they have been given special attention as we have compiled all available data that relate to their biochemical, functional, and structural properties. The α-mannosidosis mutation database is comprehensive and relational in the sense that information can be retrieved and compiled across datasets; hence, it will facilitate diagnostics and increase our understanding of the clinical and molecular aspects of α-mannosidosis. We believe that the amamutdb.no structure and architecture will be applicable for the development of databases for any monogenic disorder.
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Bases de Datos Genéticas , alfa-Manosidasa/genética , alfa-Manosidosis/genética , Alelos , Estudios de Asociación Genética , Genotipo , Mutación , Fenotipo , Conformación Proteica , Programas Informáticos , Relación Estructura-Actividad , alfa-Manosidasa/química , alfa-Manosidasa/metabolismo , alfa-Manosidosis/diagnóstico , alfa-Manosidosis/metabolismoRESUMEN
Alpha-mannosidosis (OMIM 248500) is a rare, autosomal recessive, multisystemic, progressive lysosomal storage disorder caused by a deficiency of alpha-mannosidase. It has been described in humans, cattle, domestic cats, mice and guinea pigs. In humans, alpha-mannosidosis results in progressive facial- and skeletal abnormalities, motor impairment, hearing impairment, intellectual disability, recurrent infections and immune deficiency. This review provides detailed information regarding the variability of manifestations and a description of current treatment and treatment under investigation for alpha-mannosidosis. The pathology, genetics and clinical pictures, including impairments in the activity of daily living are discussed.
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alfa-Manosidosis/diagnóstico , alfa-Manosidosis/genética , alfa-Manosidosis/terapia , Terapia de Reemplazo Enzimático , Pérdida Auditiva/diagnóstico , Pérdida Auditiva/genética , Trasplante de Células Madre Hematopoyéticas , HumanosRESUMEN
α-Mannosidosis storage disease is a rare autosomal recessive disease that is caused by a deficiency of the lysosomal enzyme α-mannosidase. In this article, a proband in China was preliminarily diagnosed as having α-mannosidosis by clinical symptoms, imaging examination, and enzyme assay. Definitive diagnosis was performed by directly sequencing the MAN2B1 gDNA and cDNA of the peripheral blood leukocyte from the patient. Finally, denaturing high-performance liquid chromatography screening, conservative analysis, and protein secondary structure prediction were used to identify the novel mutation. The results showed that the patient has compound heterozygous mutations in the MAN2B1 gene, c.856G>A (p.E286K, novel) and c.788C>T (p.P263L). Her parents are heterozygote that carry one of these two mutations respectively. Pathogenicity identification of the novel mutation showed that the p.E286K mutation is a disease-causing mutation. Our work enriches the human MAN2B1 gene mutation database. As far as we know, this research is thus far the first gene diagnosis case of a Chinese patient with α-mannosidosis.
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Mutación Missense/genética , alfa-Manosidasa/genética , alfa-Manosidosis/diagnóstico , alfa-Manosidosis/genética , Preescolar , China , Secuencia Conservada/genética , Análisis Mutacional de ADN , Enzimas/sangre , Enzimas/genética , Femenino , Humanos , Linaje , Polimorfismo de Nucleótido Simple/genética , Estructura Secundaria de ProteínaRESUMEN
Most alpha-mannosidosis patients described have been children and information on the natural course of the disorder has been based on a very limited number of observations. In order to assess the disease presentation in detail and to study disease characteristics, a study was started in 1991 and has been ongoing for over 20 years. Patients with confirmed alpha-mannosidosis were recruited through The International Society for Mannosidosis and Related Diseases (ISMRD) where families affected with alpha-mannosidosis received a questionnaire on general clinical information to be filled out by the responsible physician. The questionnaire was returned by 125 patients (64%). Of these, 45 patients were 15 years old or older at the time of evaluation. The questionnaire allowed us to assess the following features: Facial dysmorphism, columnar disease, arthritis, myopathy, hearing impairment, mental impairment, psychosis, bone disease and motor function as well as general health. This study describes the progression of alpha-mannosidosis and may be helpful in determining the clinical characteristics for assessments of prognosis.
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alfa-Manosidosis/diagnóstico , alfa-Manosidosis/fisiopatología , Adolescente , Adulto , Niño , Preescolar , Recolección de Datos , Progresión de la Enfermedad , Facies , Pérdida Auditiva/complicaciones , Humanos , Lactante , Recién Nacido , Trastornos Mentales/complicaciones , Persona de Mediana Edad , Enfermedades Musculares/complicaciones , Pronóstico , Trastornos Psicóticos/complicaciones , Estudios Retrospectivos , Encuestas y Cuestionarios , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
Although lysosomal storage disorders (LSDs) are considered individually rare, as a group they present a non-negligible frequency. Few studies have been made of populational occurrence of LSDs; they have been conducted predominantly on Caucasian populations. We studied the occurrence of LSDs in Cuba. Data from individuals who had been referred to the Institute of Neurology and Neurosurgery in Havana from hospitals all over the country between January 1990 and December 2005 were analyzed. This institute was the only laboratory to provide enzyme-based diagnostic testing for 19 LSDs in Cuba during this period. Occurrence rates were calculated by dividing the number of postnatal diagnoses by the number of births during the study period. The combined occurrence of LSDs in Cuba was 5.6 per 100,000, lower than that reported in other studies conducted on Caucasian populations. The most frequent individual LSDs were: mucopolysaccharidosis type I (1.01 per 100,000) and, surprisingly, alpha-mannosidosis (0.72 per 100,000) and fucosidosis (0.62 per 100,000). These findings may be related to specific genetic characteristics and admixture of the Cuban population. This is the first comprehensive study of the occurrence of LSDs in Cuba. We conclude that the epidemiology of these diseases can vary regionally, and we stress the need for similar surveys in other Latin American countries.