Neumotórax espontáneo en paciente con enfermedad de Fabry / Spontaneous pneumothorax in a patient with Fabry disease

La enfermedad de Fabry pertenece al grupo de enfermedades lisosomales, poco frecuentes y de origen genético. Se comporta como una enfermedad crónica, multisistémica y progresiva, que deteriora la calidad de vida y disminuye la supervivencia del paciente. La afectación pulmonar en esta enfermedad es incierta y no existen reportes en la bibliografía sobre su incidencia. Presentamos el caso de un paciente masculino con diagnóstico de enfermedad de Fabry y compromiso pulmonar(AU)

Fabry disease belongs to the group of lysosomal diseases, which are rare and of genetic origin. It behaves like a chronic, multisystemic, progressive disease that deteriorates the quality of life and decreases patient's survival.2 Lung involvement in this disease is uncertain, and there are no reports in the literature related to its incidence. We present the case of a male patient with a diagnosis of Fabry disease and lung involvement(AU)

Reporte de caso: enfermedad de Fabry en un adulto con enfermedad renal crónica y síntomas sistémicos característicos / A case report: Fabry disease in an adult with chronic kidney disease and characteristic systemic symptoms / Relato de um caso: doença de Fabry em um adulto com doença renal crônica e sintomas sistémicos característicos

Se presenta el caso de un paciente de sexo masculino, de 62 años, con antecedentes familiares de cardiopatía y enfermedad renal, y antecedentes personales de enfermedad renal crónica severa, por la que recibió trasplante renal. Es enviado a consulta cardiológica por dolores torácicos atípicos y episodios de hipotensión sintomática, se constata en el ecocardiograma: hipertrofia ventricular izquierda concéntrica y deformación miocárdica longitudinal del ventrículo izquierdo patológica. La resonancia magnética cardíaca encuentra un patrón de realce tardío sugestivo de enfermedad de Fabry, diagnóstico que se confirma con dosificación enzimática y estudio genético. Recibe tratamiento específico con una buena respuesta inicial. Esta es una enfermedad sistémica metabólica congénita en la que el diagnóstico y el tratamiento específico se realiza en la edad adulta.

It is presented a 62-year-old male patient with a family history of heart and kidney disease, and a personal history of chronic kidney disease, for which he received a kidney transplant. He was sent to the cardiology department due to atypical chest pain and episodes of symptomatic hypotension. The echocardiogram revealed: concentric left ventricular hypertrophy and pathological longitudinal myocardial deformation of the left ventricle. Cardiac magnetic resonance finds a pattern of late enhancement suggestive of Fabry disease, a diagnosis that is confirmed with enzyme dosage and genetic study. He receives specific treatment with a good initial response. This is a congenital metabolic systemic disease in which the diagnosis and specific treatment is carried out in adulthood.

Se apresenta o caso de um paciente do sexo masculino, 62 anos, com histórico familiar de cardiopatia e doença renal e histórico pessoal de doença renal crônica grave, para o qual recebeu transplante de rim. Foi encaminhado ao serviço de cardiologia por dor torácica atípica e episódios de hipotensão sintomática. O ecocardiograma revelou: hipertrofia ventricular esquerda concêntrica e deformação miocárdica longitudinal patológica do ventrículo esquerdo. A ressonância magnética cardíaca encontra um padrão de realce tardio sugestivo de doença de Fabry, diagnóstico confirmado com dosagem enzimática e estudo genético. Recebe tratamento específico com boa resposta inicial. Tratase de uma doença sistêmica metabólica congênita em que o diagnóstico e o tratamento específico são realizados na idade adulta.

Alpha-Galactosidase A Levels in Colombian Males with End-Stage Renal Disease: Ten Years of Selective Screening in Dried Blood Spots

Abstract Fabry disease is a metabolic alteration linked to an enzymatic deficiency of Alpha-Galactosidase A, this disorder compromises the sphingolipid metabolism, leading to an accumulation of lysosomal globotriaosylceramide and is inherited in an X-linked recessive way. The diagnostic of this disease, in general, requires the confirmation of below-normal levels of Alpha-Galactosidase A obtained from dried blood spot (DBS) samples, followed by an assessment of the enzyme in leukocytes. We aimed to report the Alpha-Galactosidase A values obtained in Colombian males with end-stage renal disease (ESRD) screened using dried blood spot samples during ten years. This screening was performed with samples sent to the analysis center from 6156 patients between 2006- 2016. All patients with low levels in enzyme activity (compared to the control population) were sent to confirmation through enzyme analysis in isolated leukocytes. 26 males (0.42%) with low levels of Alpha-Galactosidase A were identified (Range 0.0 - 1.14 nmol/ml/hour, cut-off: 1.15), 22 patients were subsequently measured in isolated leukocytes having a confirmation of Fabry disease in 5 patients (0.08% of total male population) (Range: 0.3 -4.7 nmol/mg prot/h). These results are similar to those reported in studies with comparable characteristics being this the first reporting frequency of Fabry disease among Colombian males with end-stage renal disease.

Difficulties in the Diagnosis of Gaucher Disease in a Low-Income Country: A Case Report from Mozambique

Abstract Introduction: Gaucher disease (GD) is one of the common lysosomal storage disorder (LSD) with an estimated frequency of one in 40,000 newborns globally. GD is an autosomal recessive condition, which results from mutations in the GBA1 gene, causing partial or complete deficiency of β-glucocerebrosidase enzyme activity, which leads to the widespread accumulation of the substrate glucosylceramide. Aims: This report presents different challenges of clinical management and communication between medical specialties to reach diagnose of any rare disease in Mozambique, a low-income country, which health system has limited infrastructure, trained personnel, and budget for diagnosis and to provide treatment for rare genetic disorders such as GD. Case Presentation: The patient was a 15-year old black female patient of Mozambican nationality born from non-consanguineous parents. Three of the four patient's siblings were healthy; one sister had died of a disease with a similar clinical features. Our patient presented with abdominal distention and hepatosplenomegaly. Blood tests revealed pancytopenia and a high level of ferritin. Liver biopsy and histologic examination revealed infiltration of the splenic parenchyma and portal area of the liver as well as enlarged histiocytic cells with granular cytoplasm. Magnetic resonance imaging showed liver enlargement, changes in the femoral heads without osteonecrosis, a pathological fracture of the third thoracic vertebrae (T3), with absence of brain and spinal cord neurological abnormalities. The biochemical investigation disclosed low levels of β-glucocerebrosidase (0.223 nmol/h/ml; normal: above 0.98) and increased levels of lyso-Gb1 (0.43 µg/ml; normal: up to 0.003). Genotyping of the GBA1 gene indicated the presence of the pathogenic variant p.Arg87Trp (R48W) in homozygosis. Discussion and Conclusion: To the best of our knowledge, this report describes the first case of GD type 1 confirmed via biochemical and molecular genetic testing in Mozambique. As awareness of the GD and rare genetic diseases among Mozambican health professionals is very limited, and resources for diagnosis are scarce in the national health system, it is possible that other cases remain undiagnosed in this low-income country.

Mutations identified in a cohort of Mexican patients with lysosomal acid lipase deficiency.

INTRODUCTION AND OBJECTIVES: Lysosomal acid lipase deficiency (LAL-D) is an autosomal recessive disease caused by mutations in the LIPA gene, located on the long arm of chromosome 10 (10q23.31). Up until now, more than 59 mutations have been described and which are the cause of a very wide clinical spectrum. The goal of this study was to identify the mutations present in Mexican pediatric patients with a diagnosis of LAL-D. MATERIALS AND METHODS: A cross-sectional study was carried out which included all the pediatric patients with LAL-D treated in a tertiary hospital in Mexico from January 2000 to June 2017. RESULTS: Sixteen patients with LAL-D were identified with a disease phenotype marked by the accumulation of cholesteryl esters. Eight distinct variants in the LIPA gene sequence were found, four pathogenic variants and four probably pathogenic. In six individuals, the variants were found in the homozygous state and ten were compound heterozygous. The eight variants were inverted, with five found on exon 4 and the others on exons 2, 8 and 10. The variant c.386A>G;p.His129Arg was the most common, being found in six of the 16 individuals (37.5%), making it much more frequent than what had previously been reported in the literature in proportion to the rest of the variants. The mutation known as E8SJM, which has been the mostly frequently found at the international level, was not the most common among this group of Mexican patients. In conclusion, Mexican patients present a different frequency of mutations associated with LAL-D in comparison to European populations.

Diagnosis of Mucopolysaccharidosis Based on History and Clinical Features: Evidence from the Bajio Region of Mexico.

Introduction Mucopolysaccharidosis (MPS) are infrequent deposit diseases; generally, the diagnosis is delayed until symptoms appear. Age or presentation is related to the severity of the disease. A substantial number of patients are misdiagnosed since they describe nonspecific initial symptoms and signs in common. The aim of this study is to describe the common characteristics of patients with mucopolysaccharidosis already diagnosed, treated in hospitals of the Guanajuato Health System, with a special focus on early manifestations in order to review early clinical suspect manifestations. Methods A multicenter, descriptive, observational study was conducted to evaluate the cases of mucopolysaccharidosis treated and diagnosed. The study was carried out in the Pediatric departments of five big important hospitals of Bajio Mexico region in the period from February to August 2016. Results Eighteen patients were identified, 13 men and five women, with an average age of 8.6 years. The most frequent mucopolysaccharidosis was type IV A (Morquio) in seven patients, followed by type I (Hurler) in four patients, three patients for type III (San Filippo), two patients for type II (Hunter), and two patients for type VI (Maroteaux-Lamie). The commonest clinical manifestations at diagnosis were dimorphism, triangular dorsal hump, skeletal alterations (genu valgus, short stature, and flat feet), and a limited range of movement in the major joints. Non-skeletal manifestations, such as an umbilical/inguinal hernia and hepato-splenomegaly, were very frequent. In a majority of patients with mucopolysaccharidosis, the radiological data of the disease were found: they were most severe in type IV and type VI, mild in type I and II, and none in MPS III. A diagnosis was made in all patients by a clinical and radiological evaluation and confirmed by an enzymatic study. Conclusions In all rare diseases, a suspicion diagnosis is based on subtle characteristics that manifest themselves in a few different organs and systems may be mild. Suspicion by the physician and the need to strengthen collaboration patterns between different specialities play an important role in the early diagnosis and treatment of these conditions.

ANÁLISIS DE LA β -GALACTOSILCERAMIDASA LEUCOCITARIA EN PACIENTES COLOMBIANOS CON SOSPECHA CLÍNICA DE ENFERMEDAD DE KRABBE, UN TAMIZAJE DE ALTO RIESGO / ANALYSIS OF β -GALACTOSILCERAMIDASE LEUKOCYTAL IN COLOMBIAN IN PATIENTS WITH SUSPECT CLINIC OF KRABBE DISEASE, A HIGH - RISK SCREENING / ANÁLISE DE β -GALACTOSILCERAMIDASE LEUKOCYTAL EM COLOMBIANO EM PACIENTES COM SUSPEITA CLINICA DA DOENÇA DE KRABBE, UMA BLINDAGEM DE ALTO RISCO HUMANOS PLACENTA

La Enfermedad de Krabbe (EK), es un desorden del metabolismo de esfingolípidos de herencia autosómica recesiva causada por la deficiencia de β-galactosilceramidasa (β-Galsil) (E.C. 3.2.1.46), defecto enzimático que causa un cuadro neurodegenerativo, hipertonía muscular y espasticidad, convulsiones, pérdida de la audición y en un 85% de los casos la muerte temprana, entre otros hallazgos. La incidencia de la EK documentada para Estados Unidos y Europa es de 1:100.000 recién nacidos, pero estudios recientes han demostrado valores mayores de 1:22.000 aproximadamente en New York. En América Latina los informes son escasos, con reportes de tamizaje de alto riesgo en Brasil y casos aislados en México, ofreciendo un panorama de subdiagnóstico importante, situación a la que no es ajena Colombia, donde no hay en la literatura referentes a la enfermedad. Se presenta entonces a la comunidad científica, un estudio de valores de actividad y de referencia para la enzima β-Galactosilceramidasa leucocitaria, a partir de 259 muestras de 110 individuos sanos y 149 pacientes con compromiso neurodegenerativo (CND). La valoración enzimática involucró dos métodos (Colorimétrico y Fluorométrico) de punto final que permitieron establecer un rango de referencia para β-Galsil en técnica Colorimétrica: 2,04-14,93 nmol/mgprot/h y en técnica fluorométrica: 0,3-4,21 nmol/mgprot/h. El estudio de tamizaje permitió identificar un paciente afectado con enfermedad de Krabbe quien presentó valores de actividad expresados en nmol/mgprot/h de 1,85 y 0,034, en forma correspondiente para las técnicas antes descritas. Un hallazgo final que permite validar los dos métodos estandarizados para el diagnóstico de la enfermedad y establecer valores de referencia en población colombiana.

Krabbe disease is a disorder of autosomal recessive sphingolipid metabolism caused by deficiency β-galactosylceramidase (β-Galsil) (EC3.2.1.46), an enzymatic defect that causes a hurt neurodegenerative, muscular hypertonia and Spasticity, convulsions, hearing loss and in 85% of cases early death, among other findings. The incidence documented for "Krabbe disease" in the United States and Europe is 1:100.000 newborns, but recent studies have shown values greater than 1:22.000 in New York. In Latin America, reports are limited, with reports of high-risk screening in Brazil and isolated cases in Mexico, providing an important underdiagnosis scenario, a situation that is not unknown in Colombia, where there is no literature on the disease. A study of activity and reference values for β-galactosylceramidase enzyme leukocytal, was then presented to the scientific community, from 259 samples from 110 healthy people and 149 patients with neurodegenerative compromise. The enzymatic evaluation involved two methods (Colorimetric and Fluorometric) that allowed the establishment of a reference range for β-Galsil in Colorimetric technique: 2.04-14.93 nmol/mgprot/h and in fluorometric technique: 0.3-4.21 nmol/mgprot/h. The screening study allowed the identification of a patient with Krabbe disease who presented activity values expressed in nmol/mgprot/h of 1.85 and 0.034, correspondingly to the techniques described above. A final finding that allows to validate the two standardized methods for the diagnosis of the disease and to establish reference values in Colombian population.

A doença de Krabbe é uma desordem do metabolismo de esfingolípidos autossômicos recessivos causada pela deficiência β-galactosilceramidase (β-Galsil) (EC 3.2.1.46), um defeito enzimático que causa uma neurodegenerativa relatório, hipertonia muscular e espasticidade, convulsões, perda auditiva e em 85% Dos casos de morte precoce, entre outros. A incidência da doença de Krabbe documentado para os Estados Unidos e na Europa é de 1:100.000 recém-nascidos, mas estudos recentes têm mostrado valores maiores do que cerca de 1:22.000, em Nova York. Na América Latina, os relatórios são escassos, com relatos de rastreio de alto risco no Brasil e casos isolados no México, proporcionando um cenário importante subdiagnóstico, a situação não é desconhecida em que a Colômbia, não há literatura Onde sobre a doença. Um estudo de atividade e valores de referência para a enzima β-galactosilceramidase leucocital, foi então apresentado comunidade científica, de 259 amostras de 110 indivíduos saudáveis e​ 149 pacientes com comprometimento neurodegenerativo. A avaliação enzimática envolveu dois métodos (Colorimétrico e Fluorométrico) que permitiram o estabelecimento de uma gama de referência para β-Galsil na técnica Colorimétrica: 2,04-14,93 nmol /mgprot/h e na técnica fluorométrica: 0,3-4,21nmol/mgprot/h. O estudo de triagem permitiu a identificação de um paciente com doença de Krabbe que apresentou valores de atividade expressados ​em nmol / mgprot / h de 1,85 e 0,034, correspondente ao das técnicas descritas acima. Uma conclusão final que valida os dois métodos padronizados para o diagnóstico da doença e estabelecer valores de referência na população colombiano.

Hampered Vitamin B12 Metabolism in Gaucher Disease?

Abstract Untreated vitamin B12 deficiency manifests clinically with hematological abnormalities and combined degeneration of the spinal cord and polyneuropathy and biochemically with elevated homocysteine (Hcy) and methylmalonic acid (MMA). Vitamin B12 metabolism involves various cellular compartments including the lysosome, and a disruption in the lysosomal and endocytic pathways induces functional deficiency of this micronutrient. Gaucher disease (GD) is characterized by dysfunctional lysosomal metabolism brought about by mutations in the enzyme beta-glucocerebrosidase (Online Mendelian Inheritance in Man (OMIM): 606463; Enzyme Commission (EC) 3.2.1.45, gene: GBA1). In this study, we collected and examined available literature on the associations between GD, the second most prevalent lysosomal storage disorder in humans, and hampered vitamin B12 metabolism. Results from independent cohorts of patients show elevated circulating holotranscobalamin without changes in vitamin B12 levels in serum. Gaucher disease patients under enzyme replacement therapy present normal levels of Hcy and MMA. Although within the normal range, a significant increase in Hcy and MMA with normal serum vitamin B12 was documented in treated GD patients with polyneuropathy versus treated GD patients without polyneuropathy. Thus, a functional deficiency of vitamin B12 caused by disrupted lysosomal metabolism in GD is a plausible mechanism, contributing to the neurological form of the disorder but this awaits confirmation. Observational studies suggest that an assessment of vitamin B12 status prior to the initiation of enzyme replacement therapy may shed light on the role of vitamin B12 in the pathogenesis and progression of GD.

Mucopolisacaridosis II: nueva mutación patogénica en gen IDS / Mucopolysaccaridosis II: new pathogenic mutation in IDS gene)

La mucopolisacaridosis tipo II es una enfermedad lisosomal producida por la deficiencia de la enzima iduronato 2 sulfatasa. Es una condición infrecuente de herencia recesiva ligada al X, que puede producir importante discapacidad progresiva. El análisis molecular es una técnica útil en la confirmación diagnóstica, que además permite detección de portadores asintomáticos, brindando la oportunidad de asesoría genética. Se presenta el caso de un paciente con mucopolisacaridosis tipo II, en quien se documentó una nueva mutación patogénica en el Gen IDS.

Mucopolysaccharidosis type II is a lisosomal disorder caused by a deficiency of the iduronate 2 sulphatase enzyme. It is a rare metabolic disease with an X linked recessive inheritance that may cause important progressive disability. Molecular analysis is a useful technique to confirm diagnosis and to identify asymptomatic carriers, thus allowing genetic counseling. We report the case of a patient with Muchopolysacharidosis type II with a new pathogenic mutation in the IDS gene.

Guidelines for diagnosis and treatment of Hunter Syndrome for clinicians in Latin America.

This review aims to provide clinicians in Latin America with the most current information on the clinical aspects, diagnosis, and management of Hunter syndrome, a serious and progressive disease for which specific treatment is available. Hunter syndrome is a genetic disorder where iduronate-2-sulfatase (I2S), an enzyme that degrades glycosaminoglycans, is absent or deficient. Clinical manifestations vary widely in severity and involve multiple organs and tissues. An attenuated and a severe phenotype are recognized depending on the degree of cognitive impairment. Early diagnosis is vital for disease management. Clinical signs common to children with Hunter syndrome include inguinal hernia, frequent ear and respiratory infections, facial dysmorphisms, macrocephaly, bone dysplasia, short stature, sleep apnea, and behavior problems. Diagnosis is based on screening urinary glycosaminoglycans and confirmation by measuring I2S activity and analyzing I2S gene mutations. Idursulfase (recombinant I2S) (Elaprase(®), Shire) enzyme replacement therapy (ERT), designed to address the underlying enzyme deficiency, is approved treatment and improves walking capacity and respiratory function, and reduces spleen and liver size and urinary glycosaminoglycan levels. Additional measures, responding to the multi-organ manifestations, such as abdominal/inguinal hernia repair, carpal tunnel surgery, and cardiac valve replacement, should also be considered. Investigational treatment options such as intrathecal ERT are active areas of research, and bone marrow transplantation is in clinical practice. Communication among care providers, social workers, patients and families is essential to inform and guide their decisions, establish realistic expectations, and assess patients' responses.