MUCOPOLYSACCHARIDOSIS TYPE 2: NARRATIVE REVIEW

Mucopolysaccharidosis type II, also known as Hunter syndrome, is a rare, progressive, multisystemic lysosomal storage disease caused by de?ciency of iduronate 2 sulfatase, an enzyme responsible for the degradation of the mucopolysaccharides dermatan (DS) and keratan sulfate (QS), causing their accumulation at the lysosomal level. It is an X-linked disease, therefore it is common to ?nd most cases in men, rarely in women, it is considered an orphan disease given an incidence of approximately 1/100,000 live births. Various phenotypes of severe (2/3) and attenuated disease have been described. The diagnosis is based on clinical ?ndings and the measurement of mucopolysaccharides DS and QS in urine, which are elevated, con?rmed by determining the enzyme de?ciency in serum, leukocytes and ?broblasts. It has been observed that in patients with enzyme replacement therapy somatic symptoms have decreased, however there are several studies of alternative therapies in the future, including gene therapy as an alternative in the future

GM1 gangliosidosis: a case report / Gangliosidose GM1: um relato de caso

RESUMEN La gangliosidosis GM1 es un trastorno lisosomal caracterizada por la acumulación de gangliósido GM1 (glucoesfingolípido) en el sistema nervioso central (SNC) y visceral, debido a la deficiencia de la enzima beta-galactosidase (hidrolasa lisosomal). Afecta principalmente al SNC y las vísceras y produce importantes anomalías esqueléticas, que a menudo ocurren con la presencia de linfocitos vacuolados en la muestra de la sangre periférica o médula ósea. Tiene tres formas de presentación, lo que dificulta aún más su identificación debido al amplio espectro clínico. El presente estudio tiene como objetivo describir un caso de gangliosidosis GM1 en un paciente masculino, nacido a las 38 semanas. Hasta el momento, no existe un tratamiento efectivo para la gangliosidosis GM1, es decir, el portador de la enfermedad solo recibe medidas sintomáticas y paliativas. Por tanto, el diagnóstico precoz de la enfermedad es de suma importancia, ya que su única forma de prevención, actualmente, es a través del consejo genético.

Enfermedad de Fabry. Manejo anestésico en trasplante renal, a propósito de un caso / Fabry disease. Anesthetic management in kidney transplant, report of case

INTRODUCTION: Fabry disease (FD) also known as Anderson Fabry disease is a rare disorder linked to the X chromosome, which produces mutations in the coding of the GLA gene involved in the production of the enzyme -galactosidase A, whose complete or partial deficiency leads to the intracellular accumulation of globotriaosylceramide and glycosphingolipids. CLINICAL CASE: We present the case of a 39 year old female patient admitted to hospital with a diagnosis of terminal chronic kidney disease of 8 years of evolution as a possible cause of nephropathy, Fabry disease diagnosed in a patient, after detailed studies, kidney transplantation is considered for improvement of your lifestyle. DISCUSSION: Patients with Fabry disease should be considered as high risk surgical and anesthetic should have a strict assessment and evaluation of cardiovascular and respiratory function, to anticipate the complications associated with reperfusion of the transplanted organ. CONCLUSION: The use of balanced or intravenous modality has been described among the anesthetic possibilities without reaching a consensus so far, however the two modalities can be used and their analgesic management can be performed with plexus blocks or regional anesthesia.

INTRODUCCIÓN: La enfermedad de Fabry (FD) también conocida como enfermedad de Anderson Fabry es un trastorno raro ligado al cromosoma X, que produce mutaciones en la codificación del gen GLA partícipe en la producción de la enzima α-galactosidasa A, cuya deficiencia completa o parcial conduce a la acumulación intracelular de globotriaosilceramida y glicosfingolípidos. CASO CLÍNICO: Se presenta el caso de una paciente femenina de 39 años de edad ingresada a hospitalización con diagnóstico de enfermedad renal crónica terminal de 8 años de evolución como posible causa de nefropatía, enfermedad de Fabry diagnosticada en paciente, tras estudios detallado se considera trasplante renal para mejora de su estilo de vida. DISCUSIÓN: Los pacientes con enfermedad de Fabry deben ser considerados como de alto riesgo quirúrgico y anestésico, deben contar con una estricta valoración y evaluación sobre la función cardiovascular y respiratoria, para así preveer las complicaciones asociadas a la reperfusión del órgano trasplantado. CONCLUSIÓN: Se han descrito entre las posibilidades anestésicas el uso de modalidad balanceada o intravenosa sin llegar aún a un consenso hasta el momento, sin embargo, las dos modalidades pueden ser utilizadas y su manejo analgésico se puede realizar con bloqueos del plexo o anestesia regional.

Detection of swainsonine and calystegines in Convolvulaceae species from the semiarid region of Pernambuco / Detecção de swainsonina e calisteginas em espécies de Convolvulaceae da região semiárida de Pernambuco

Numerous plant species worldwide including some Ipomoea (Convolvulaceae) and Sida (Malvaceae) species in Brazil cause lysosomal storage disease in herbivores and are known to contain swainsonine and calystegines as the main toxic compounds. The aim of this work was to determine swainsonine and calystegines concentrations in species of Convolvulaceae from the semiarid region of Pernambuco. Seven municipalities in the Moxotó region were visited and nine species were collected and screened for the presence of swainsonine and calystegines using an HPLC-APCI-MS method. The presence and concentration of these alkaloids within the same and in different species were very variable. Seven species are newly reported here containing swainsonine and/or calystegines. Ipomoea subincana contained just swainsonine. Ipomoea megapotamica, I. rosea and Jacquemontia corymbulosa contained swainsonine and calystegines. Ipomoea sericosepala, I. brasiliana, I. nil, I. bahiensis and I. incarnata contained just calystegines. The discovery of six Ipomoea species and one Jacquemontia species containing toxic polyhydroxy alkaloids reinforces the importance of this group of poisonous plants to ruminants and horses in the semiarid region of Pernambuco. Epidemiological surveys should be conducted to investigate the occurrence of lysosomal storage disease associated to these new species.(AU)

Numerosas espécies de plantas em todo o mundo, incluindo algumas espécies de Ipomoea (Convolvulaceae) e Sida (Malvaceae) no Brasil, causam doença de armazenamento lisossomal em herbívoros e são conhecidas por conterem swainsonina e calisteginas como princípios tóxicos. O objetivo deste trabalho foi determinar a concentração de swainsonina e calisteginas em espécies de Convolvulaceae da região semiárida de Pernambuco. Sete municípios na região do Sertão do Moxotó foram visitados, onde foram coletadas amostras das folhas de nove espécies de Convolvulaceae para avaliação da presença de swainsonina e calisteginas utilizando-se cromatografia líquida com espectrometria de massa. A presença e concentração destes alcaloides nas folhas de plantas da mesma espécie e dentre as espécies foram muito variáveis. Seis novas espécies de Ipomoea e uma espécie de Jacquemontia contendo swainsonina e/ou calisteginas são relatadas neste estudo. Ipomoea subincana continha apenas swainsonina. Ipomoea megapotamica, I. rosea e Jacquemontia corymbulosa continham swainsonina e calisteginas. Ipomoea sericosepala, I. brasiliana, I. nil, I. bahiensis e I. incarnata continham apenas calisteginas. A descoberta de novas espécies de Ipomoea e Jacquemontia contendo alcaloides polihidroxílicos tóxicos reforçam a importância deste grupo de plantas tóxicas para ruminantes e equinos na região semiárida de Pernambuco. Pesquisas epidemiológicas devem ser realizadas para investigar a ocorrência de doença de depósito lisossomal associada a essas novas espécies.(AU)

Hypomyelinogenesis associated with transplacental poisoning by Sida carpinifolia (Malvaceae) in fetus and newborn calves / Hipomielinogênese associada à intoxicação transplacentária por Sida carpinifolia (Malvaceae) em fetos e neonatos bovinos

Sida carpinifolia is a plant responsible for poisoning several species of animals. This paper describes Hypomyelinogenesis in fetuses and neonates of cattle that consumed S. carpinifolia. Neonates manifested ataxia and muscle tremors. Two bovine newborns and four fetuses were necropsied and showed no significant gross changes. Histopathologic findings included vacuolation of pancreatic acinar cells, thyroid follicular cells, hepatocytes, cells of renal tubules and neurons of the fetus and the white matter of the telencephalic frontal lobe of the neonates and also revealed axonal spheroids in the brain of the fetuses and neonates. The lectin-histochemical evaluation shoved staining for the lectins Con-A, WGA and s-WGA. The Luxol Fast Blue staining revealed a marked decrease of myelin in the brain of all the fetuses and a moderate decrease in the neonates. Histologic and lectin-histochemic findings indicate that the consumption of S. carpinifolia by pregnant bovine females can cause hypomyelinogenesis in fetuses and neonates.(AU)

Sida carpinifolia é uma planta responsável por intoxicar várias espécies animais. Este artigo descreve hipomielinogênese em fetos e neonatos de bovinos que consumiram S. carpinifolia. Os neonatos manifestaram ataxia e tremores musculares. Dois neonatos e quatro fetos bovinos foram necropsiados e não havia alterações macroscópicas significativas. Os achados histopatológicos incluíram vacuolização de células acinares do pâncreas, células foliculares da tireoide, hepatócitos, células renais tubulares e neurônios nos fetos. Nos neonatos havia vacuolização na substância branca do lobo frontal telencefálico, além de esferoides axonais no encéfalo dos fetos e dos recém-nascidos. A avaliação lectino-histoquímica demonstrou marcação para as lectinas Con-A, WGA e s-WGA. A coloração de Luxol Fast Blue revelou diminuição acentuada da mielina no telencéfalo de todos os fetos e diminuição moderada nos neonatos. Os achados histológicos e lectina-histoquímicos indicam que o consumo de S. carpinifolia por fêmeas bovinas gestantes pode causar hipomielinogênese em fetos e neonatos.(AU)

Ipomoea brasiliana poisoning on buck reproduction / Efeitos da intoxicação por Ipomoea brasiliana na reprodução de caprinos

ABSTRACT: Swainsonine-containing plants comprise a group of important poisonous plants in Brazil. This research aimed to characterize both the behavioral changes related to reproduction and appearance of lesions in the reproductive system of bucks poisoned by Ipomoea brasiliana. I. brasiliana plants were collected and administered at a dose of 4g/kg (800µg swainsonine/kg) to two groups of bucks for 45 days. Goats from Group I were euthanized on the 46th day of the experiment, and goats from Group II were euthanized on the 120th day. Group III was composed of goats that did not receive I. brasiliana and were euthanized on the 120th day of the experiment. Reproductive behavioral changes were observed starting on day 20 and were characterized by an absence of courtship behavior, and Flehmen reflex, decrease or loss of libido and inability to perform mating. After 120 days, Group II goats showed no regression of the changes in their reproductive behavior or improvement of their seminal parameters. The main defects observed in the sperm of goats that consumed I. brasiliana were cytoplasmatic droplets, bent tails and detached tails. The main histopathological findings were reported in tests, with cytoplasmic vacuolization of germline and Sertoli cells, generalized impairment of spermatogonia maturation with exfoliation of degenerative cells, cell fragments, rare abnormal spermatocytes in the seminiferous lumen and disappearance of Leydig cells. Results of this study confirmed the hypothesis that I. brasiliana causes testicular degeneration in male goats.

RESUMO: Este trabalho teve como objetivo caracterizar as mudanças comportamentais relacionadas a reprodução e lesões no sistema reprodutor de caprinos intoxicados por Ipomoea brasiliana. A planta foi coletada e administrada na dose de 4g/kg (800μg swainsonina/kg) para dois grupos de caprinos durante 45 dias. Os caprinos do Grupo I foram eutanasiados no 46º dia do experimento e os caprinos do Grupo II no 120º dia. O Grupo III foi constituído por caprinos que não receberam I. brasiliana e foram eutanasiados no 120º dia de experimento. Alterações comportamentais reprodutivas foram observadas a partir de 20 dias de experimento e consistiram em ausência do comportamento de corte, ausência de reflexo de Flehmen, diminuição ou perda de libido e incapacidade de realizar a monta natural. Após 120 dias, os caprinos do Grupo II não apresentaram regressão de alterações reprodutivas. Os principais defeitos observados no sêmen dos caprinos que consumiam I. brasiliana foram gotas citoplasmáticas, caudas dobradas e caudas destacadas. Os principais achados histopatológicos consistiram em vacuolização citoplasmática das células da linhagem germinativa e células de Sertoli; comprometimento generalizado da maturação das espermatogônias com esfoliação de células degeneradas; presença de fragmentos celulares e raros espermatócitos anormais no lúmen dos túbulos seminíferos e ausência de células de Leydig. Os resultados confirmam a hipótese de que o consumo de I. brasiliana causa degeneração testicular em caprinos.

Spontaneous poisoning by Sida carpinifolia (Malvaceae) in horses / Intoxicação natural por Sida carpinifolia em equinos

Sida carpinifolia poisoning causes a chronic neurodegenerative disorder associated with lysosomal storage by indolizidine alkaloids (swainsonine). The epidemiological, clinical, pathological and lectin histochemistry findings of an outbreak of natural poisoning by S. carpinifolia in horses in Rio Grande do Sul state, Brazil, are described. Five horses from a total of 15 that were kept on native pasture with large amounts of S. carpinifolia presented during 90 days clinical signs of progressive weight loss, incoordination, stiff gait and ramble, in addition to exacerbated reactions and locomotion difficulty after induced movement. Four horses died, and one of them was submitted for necropsy. At necropsy, no significant gross lesions were observed. Histological findings observed in the central nervous system were characterized by swollen neurons with cytoplasm containing multiple microvacuoles; these abnormalities were more severe in the thalamus, hippocampus, cerebellum and pons. Using lectin histochemistry, the pons and hippocampus sections stained positive for commercial lectin Con-A, sWGA and WGA. This study aimed to detail S. carpinifolia poisoning in horses to be included in the differential diagnoses of neurological diseases of horses.(AU)

A intoxicação por Sida carpinifolia é uma desordem neurodegenerativa crônica associada ao acúmulo lisossomal pelo alcaloide indolizidínico, denominado swainsonina. Descrevem-se os achados epidemiológicos, clínicos, patológicos e de lectina-histoquímica de um surto de intoxicação natural por S. carpinifolia em equinos no Rio Grande do Sul, Brasil. De um total de 15 equinos, cinco equinos mantidos em campo nativo com grande quantidade de S. carpinifolia apresentaram sinais clínicos de emagrecimento progressivo, incoordenação, andar rígido e deambulação, além de dificuldade de locomoção com reações exacerbadas após estímulos ao movimento em um período de 90 dias de evolução clínica. Quatro equinos vieram a óbito e um foi submetido ao exame de necropsia. À necropsia, não foram observadas lesões macroscópicas. Os achados histológicos observados no sistema nervoso central caracterizaram-se por aumento de tamanho dos neurônios, com citoplasma contendo microvacúolos; tais alterações foram observadas com maior intensidade em tálamo, hipocampo, cerebelo e ponte. Na lectina-histoquímica, fragmentos de ponte e hipocampo marcaram positivamente para as lectinas comerciais Con-A, sWGA e WGA. Este trabalho visa alertar a ocorrência da intoxicação por S. carpinifolia em equinos, a qual deve ser incluída como diagnóstico diferencial dentre as doenças neurológicas de equinos.(AU)

Ocular Findings in Mucolipidosis Type II

PURPOSE: To report ocular findings of a mucolipidosis type II patient with novel mutation. CASE SUMMARY: A 10-year-old boy visited our pediatric genetic metabolic clinic for evaluation of his overall developmental delay and short stature. The boy was diagnosed with mucolipidosis type II (I-cell disease) using plasma enzyme assay and DNA sequencing of the GNPTAB gene mutation. An ophthalmologic investigation was then performed, and a depressed nasal bridge, broad nose, and swelling in the upper lid of both eyes were noted. The best corrected visual acuity was 0.32 and 0.1 and the intraocular pressure was 35 mmHg and 24 mmHg in the right and left eyes, respectively. The anterior chamber angles of both eyes were normal and mild cornea opacity in both eyes was observed. Fundus examination revealed retinal atrophy with folds in both eyes, as well as optic disc edema and optic atrophy in the right and left eyes, respectively. Atherosclerotic changes in the retinal vessels and cystoid macular edema in the left eye were observed, and ocular ultrasound revealed increased posterior sclera thickness in both eyes. CONCLUSIONS: Ocular manifestations of mucolipidosis type II are not currently well-known, and differentiation from other metabolic disorders may be difficult. An ophthalmic work-up can assist in diagnosis, and regular ophthalmic examinations should be used to maintain visual function in mucolipidosis patients.

Outcome of Gaucher Disease in India: Lessons from Prevalent Diagnostic and Therapeutic Practices.

Objectives: To study disease severity and response to enzyme replacement therapy in Gaucher disease. Methods: Updated data was captured from records of 37 patients (35 reported previously) with confirmed diagnosis of Gaucher disease from January 1995 through December 2011 (31, 83.8 %) and prospectively from January 2012 through June 2013 (6, 16.2 %). Severity of manifestations was determined by Gaucher disease Severity Score Index. Response to enzyme replacement therapy was assessed in terms of attainment of therapeutic goals. Results: Moderate to severe manifestations (domain score of > 2) were observed in treated patients at baseline (83%, 58%, 66% and 25% for anemia, thrombocytopenia, hepatomegaly and leucopenia, respectively and 100% for splenomegaly and elevated plasma chitotriosidase). None of the 11 patients treated with synthetic enzyme (average annual dose 23 to 53 units/kg) attained all therapeutic goals in the recommended time frame, particularly the visceral, skeletal and growth domains. Conclusions: Early onset of moderate to severe disease in Indian patients mandates early therapy with optimum doses to ensure attainment of all recommended therapeutic goals.

Biópsia hepática como método diagnóstico para intoxicação por plantas que contém swainsonina / Liver biopsy as diagnostic method for poisoning by swainsonina-containing plants

Neste trabalho objetivou-se avaliar a técnica de biópsia hepática como um teste de valor diagnóstico para intoxicações por plantas que contém swainsonina. Para isso, reproduziu-se experimentalmente a doença com as folhas secas de Ipomoea marcellia contendo 0,02% de swainsonina em caprinos. O Grupo I foi constituído por 6 caprinos que receberam a planta misturada a ração na dose de 4g/kg (0,8mg de swainsonina/kg) até a observação dos primeiros sinais clínicos neurológicos. Outros dois caprinos que não receberam a planta na dieta constituíram o grupo controle (Grupo II). Foram realizadas biópsias hepáticas pela técnica percutânea cega com agulha de Menghini, no dia zero e com intervalos semanais nos caprinos do experimento. As biópsias hepáticas foram fixadas em formol tamponado 10%, processadas rotineiramente, coradas pela hematoxilina-eosina e histoquímica de lectinas. Vacuolização hepatocelular similar àquelas descritas em caso de doença de depósito lisossomal foram identificadas em todos os caprinos do Grupo I no 7º dia de experimento nas amostras coradas pela hematoxilina-eosina. Em relação à histoquímica de lectinas, marcações consistentes foram obtidas com as lectinas Concanavalia ensiformis (Con-A) e Triticum vulgaris (WGA). Concluiu-se que a avaliação histológica rotineira de biópsias hepáticas pode ser usada no diagnóstico de intoxicações por plantas que contem swainsonina, mesmo em caprinos que não apresentam sinais clínicos, e que a histoquímica de lectinas pode ser usada como método diagnóstico complementar.

With the aim to investigate the use of hepatic biopsies for the diagnosis of poisoning by swainsonine-containing plants, dry leaves of Ipomoea marcellia containing 0.02% of swainsonine were administered to goats. Group I, with six goats, ingested 4g/kg of dry plant (0.8mg of swainsonina/kg) daily until the observation of the first neurologic signs. Two goats that did not receive the plant were used as control (Group II). Hepatic biopsies with the Menghini needle were performed by the percutaneous technique at day zero and at weekly intervals after the start of the administration of I. marcellia. Biopsy samples were fixed in 10% formaline, processed routinely, and stained by hematoxilin-eosin and by lectins histochemistry. Hepatocellular vacuolization similar to those described in cases of lysosomal storage disease were identified in all goats of Group I from the seven day of plant consumption in the samples satained with hematoxylin-eosin. Using lectin histochemistry, consistent labellings were observed with Concanavalia ensiformis (Con-A) e Triticum vulgaris (WGA). It is concluded that routinely histological evaluation of liver biopsies can be used in the diagnosis of poisoning by swainsonine containing plants, even in goats without clinical signs, and lectin histochemistry which can be used as supplementary diagnostic method.

CTNS gene mutation leads to cysteine nephropathy combined with corneal crystal in young child / 临床儿科杂志

Objective To explore the diagnosis of cystinosis.Methods The clinical and biochemical information, and gene detection results in a child with cystinosis was retrospective analyzed.Results Four-year-old female presented with photophobia and corneal crystal was found by ophthalmic examination at 2 years old, bilateral kidney stone was found, accompanied by development delay and rickets at 3 years old. Gas chromatography analysis in urine showed that a variety of amino acids were increased, and urine sugar and urinary micro-protein were also increased, which were in accordance with fanconi syndrome. The blood free carnitine was decreased, ester acyl carnitine spectrum was normal, and multi-amino acids such as lysine, valine and arginine were decreased. Gene analysis showed a homozygous mutation of c.696C>G (p.323 N>K) inCTNS gene, which was a known mutation. Both her parents were carrier of heterozygous mutation of c.696C>G inCTNS gene.Conclusion Child with kidney stone, renal damage, combined by multi-system damage such as eyes, bone, and thyroid should be paid attention to identify the cystinosis.

A propósito de un caso de gangliosidosis GM-2 tipo II: enfermedad de Sandhoff / A propos of a case of gangliosidosis GM. Type II. Sandhoff disease

Las gangliosidosis son un conjunto de enfermedades hereditarias de almacenamiento lisosómico, debidas a un acúmulo de gangliósidos, sobre todo en las neuronas. La causa es la disfunción de alguna de las enzimas lisosómicas de la ruta de degradación de los gangliósidos. Existen varias formas de gangliosidosis, como son la GM1 y GM2. Se presentó el caso de una paciente de 33 años de edad, que había sido diagnosticada anteriormente de esclerosis lateral amiotrófica. Por varios síntomas presentados se le realizan una serie de exámenes complementarios, los cuales arrojan como resultado una gangliosidosis GM-2 tipo II o enfermedad de Sandhoff.

Gangliosidosis are a group of hereditary diseases of lysosomal storage, due to an accumulation of gangliosides, especially in the neurons. The cause is the dysfunction of several lysosomal enzymes in the way of the gangliosides degradation. There are several forms of gangliosidesis, like GM1 and GM2. We present the case of a 33-years-old patient who was previously diagnosed with lateral amyotrophic sclerosis. Because of several symptoms he presented we carried out some complementary exams showing as a result a gangliosidosis GM-2 Type II or Sandhoff disease.

Enfermedad de Tay-Sachs / Tay-Sachs disease

La enfermedad de Tay-Sachs es un trastorno neurodegenerativo progresivo de herencia autosómica recesiva. Se debe a la deficiencia de la enzima β-hexosaminidasa A, que provoca una acumulación de gangliósidos GM2 en los lisosomas. Se incluye dentro de las esfingolipidosis. De las esfingolipidosis que presentan mancha rojo cereza en la mácula, la enfermedad de Tay-Sachs es la única en la que no se evidencia hepatoesplenomegalia. La variante más frecuente se inicia en la lactancia. Se presenta un lactante del sexo masculino al que se le realizó el diagnóstico de esta entidad a los 8 meses de edad. A partir de los 4 meses comenzó a presentar una reacción de sobresalto. A los 6 meses comenzó a perder habilidades previamente adquiridas y crisis epilépticas mioclónicas. Se constató una disminución de la actividad específica de la enzima hexosaminidasa A en leucocitos.

Tay-Sachs disease is a progressive autosomal recessive inherited neurodegenerative disorder caused by Beta-hexosaminidase A enzyme deficiency that in turn provokes GM2 ganglioside accumulation in the lysosomes. It is included in the sphyngolipidoses classification. Among the sphyngolipidoses that present with cherry-red spot in the macula, Tay-Sachs disease is the only one that does not show hepatosplenomegaly. The most frequent variant begins at the breast-feeding phase. This report presented a male nursling who was diagnosed with Tay-Sachs disease at the age of 8 months. At 4 months of age, he had begun getting some fright reactions. At 6 months-old, he began losing his previously acquired skills and suffering myoclonic seizures. The cause was the reduced specific activity of the hexosaminidase A enzyme in leukocytes.

Gangliosidosis generalizada tipo 1 / Generalized gangliosidosis type 1

La gangliosidosis generalizada tipo 1 es una enfermedad de acúmulo lisosomal producida por mutaciones en el gen de la enzima b-galactosidasa, caracterizada fundamentalmente por toma del sistema nervioso central, la visceromegalia, disostosis ósea y dimorfismo facial. Se presenta el caso de un lactante varón, hijo de padres no consanguíneos, de 5 meses de edad, Apgar 6/8 debido a hipoxia neonatal, con historia de múltiples ingresos por enfermedad diarreica e infecciones respiratorias. Es remitido a la Consulta de Genética Clínica por retardo del desarrollo psicomotor, macrocráneo y hepatomegalia, además de máculas hipercrómicas en piel. En el examen físico se encontraron evidencias de una posible afectación por enfermedad metabólica lisosomal. Entre las enfermedades a descartar estaban la galactosialidosis, de características clínicas similares, y la enfermedad de Morquio, con diferente presentación clínica pero idéntico defecto enzimático

Generalized or GM 1 gangliosidosis is a lysosomal storage disease caused by mutations in the enzyme b-galactosidase gene, mainly characterized by affecting the central nervous system, visceromegalia, osseous dysostosis and facial dimorphism. This is the case of a male nursling born to non-consanguineous parents, 5 months of age, Apgar index of 6/8 due to neonatal hypoxia, with a history of several admissions to hospital because of diarrheal disease and respiratory infections. He was referred to the clinical genetic service since he presented with retarded psychomotor development, macrocrania and hepatomegalia, in addition to hyperchromic skin spots. The physical exam found evidence of possible effects by lysosomal metabolic disease. Among the diseases to be ruled out for the diagnosis were galactosialidosis of similar clinical characteristics and Morquio B disease with different clinical presentation but identical enzymatic deficiency

Enfermedad de Fabry Descripción de un caso y su evolución en terapia de reemplazo enzimático / Fabry disease Description of a case and its evolution with enzyme replacement therapy

La enfermedad de Fabry es un trastorno hereditario de depósito lisosomal progresivo y multisistémico del catabolismo de los glicoesfingolípidos, ligado al cromosoma X, que es causado por un defecto en el gen que cataliza la enzima lisosomal alfa-galactosidasa A (alfa-GAL A), y origina el depósito intracelular, especialmente de globotriaosil-ceramida (Gb-3), en el endotelio vascular y otros tejidos. La deficiencia parcial o total de la actividad de la enzima lisosomal conduce a la incapacidad de catabolizar ciertos glicoesfingolípidos causando el daño principal, es decir, el depósito intralisosomal de sustrato Gb-3 en diferentes tipos de células. En particular, son afectadas progresivamente las células vasculares endoteliales, lo cual puede causar isquemia tisular e infarto. Es una enfermedad progresiva que causa manifestaciones derivadas de la disfunción del órgano afectado por los depósitos, principalmente riñón, corazón, sistema nervioso, tracto gastrointestinal y piel, aunque puede participar cualquier órgano y sistema de la economía. Antes de la disponibilidad de la terapia de reemplazo enzimático, el tratamiento para esta enfermedad consistía principalmente de cuidados sintomáticos y medidas correctivas no específicas. Se describen las características clínicas y la evolución de un hombre de 47 años con enfermedad de Fabry en terapia de reemplazo enzimático. (ActaMed Colomb 2014; 39: 202-206).

Fabry disease is an inherited disorder of progressive and multisystemic lysosomal storage of glycosphingolipids catabolism, X-linked, which is caused by a defect in the gene that catalyzes the lysosomal enzyme alpha-galactosidase A (alpha-GAL A), and causes the intracellular deposition, especially of globotriaosyl ceramide (Gb3) in the vascular endothelium and other tissues. Partial or total deficiency of the lysosomal enzyme activity leads to the inability to catabolize certain glycosphingolipids causing the main damage, namely the intralysosomal deposit of Gb3 substrate in different cell types. In particular, vascular endothelial cells are progressively affected, which may cause tissue ischemia and infarction. It is a progressive disease that causes manifestations derived from the dysfunction of the organ affected by the deposits, mainly kidney, heart, nervous system, gastrointestinal tract and skin, although any organ and system of the economy may be involved. Before the availability of enzyme replacement therapy, treatment for this condition consisted mainly of symptomatic care and no specific remedies. Clinical characteristics and evolution of a 47 year old man with Fabry disease on enzyme replacement therapy are described. (Acta Med Colomb 2014; 39: 202-206).

The clinical and genetic features of early-onset globoid cell leukodystrophy in one boy / 临床儿科杂志

Objective To investigate the clinical, biochemical and genetic features of a Chinese boy with early-onset glo-boid cell leukodystrophy (GLD). Methods The clinical and genetic data of a rare case of early-onset GLD were retrospectively analysed. Results At 2 months after birth, the boy showed progressive psychomotor regression. At 4 months of age when the boy was taken to a doctor, the pyramidal sign was positive. The cranial MRI showed that the body of the lateral cerebral ventri-cles was slightly enlarged and the brain ditch crack of frontal-temporal-parietal lobe was widened and deepened. On his brain CT scan, high signals in bilateral basal ganglia, thalami, cerebellar hemisphere were observed.β-galactosylceramidase (GALC) ac-tivity in the peripheral leucocytes was signiifcantly decreased (3.9 nmol/g protein.h). On his GALC gene, one homozygous novel mutation c.868C>T on exon 8 was found, which resulted in the amino acid change on p.R290C proteins. Conclutions Early-on-set GLD is a rare autosomal-recessive hereditary lysosomal storage disease with a terrible prognosis, in which beta-galactose glu-coside enzyme deifciency is induced by GALC gene mutation. The diagnosis of early-onset GLD is dififcult and should depend on enzyme assay and gene testing.

Doença de depósito lisossomal induzida pelo consumo de Ipomoea verbascoidea (Convolvulaceae) em caprinos no semiárido de Pernambuco / Lysosomal storage disease induced by the consumption of Ipomoea verbascoidea (Convolvulaceae) in goats at northeastern Brazil

The aim of this paper was to reproduce the poisoning of Ipomoea verbascoidea in goats and describe the epidemiological, clinical and pathological aspects of spontaneous poisoning by this plant in Pernambuco. For this, we studied the epidemiology of the disease in seven municipalities in the semiarid region of the State. Three spontaneously poisoned goats were examined and then euthanized and necropsied (Group I). To reproduce the disease, the dried leaves of I. verbascoidea containing 0.02% swainsonine were supplied at doses of 4g/kg (0.8mg swainsonine/kg) to two groups of three animals. The goats in Group II received daily doses of the plant during 40 days and were euthanized on the 41st day of the experiment. Goats from Group III received daily doses of the plant during 55 days and were euthanized on the 120th day of the experiment. Other three goats constituted the control group (Group IV). In experimental groups, the brain lesions were evaluated by histopathology; additionally the cerebellar lesions were evaluated by morphometry, by measuring the molecular layer thickness, the number of Purkinje cells and the area of the cell bodies of these cells. The main clinical signs and microscopic lesions in goats poisoned were similar to those reported by swainsonine containing plants. In goats of GII and GIII, the first nervous signs were observed between 22th and 29th days; clinically, the disease developed by these animals was similar to the spontaneous cases. The goats of GIII did not recover from the neurologic signs. These results show that the consumption of the plant by 26-28 days after observation of the first clinical signs is enough to cause irreversible damage. By morphometric analysis, the molecular layer of the cerebellum of the goats of Group I and III were thinner than those of goats in the control group, and Purkinje neurons were atrophic. It is suggested that these changes are responsible for the neurological picture observed in goats that stop eating the plant and have sequelae of poisoning.

O objetivo deste trabalho foi reproduzir a intoxicação por Ipomoea verbascoidea em caprinos e descrever os aspectos epidemiológicos, clínicos e histopatológicos da intoxicação espontânea por essa planta no Estado de Pernambuco. Para isso, realizou-se o acompanhamento da epidemiologia da doença em sete municípios do semiárido pernambucano. Três caprinos espontaneamente intoxicados foram examinados e, em seguida eutanasiados e necropsiados (Grupo I). Para reproduzir experimentalmente a doença, as folhas secas de I. verbascoidea contendo 0,02% de swainsonina, foram fornecidas na dose de 4g/kg (0,8mg de swainsonina/kg) a dois grupos de três animais. Os caprinos do Grupo II receberam a planta diariamente por 40 dias e foram eutanasiados no 41º dia de experimento. Os caprinos do Grupo III receberam a planta diariamente por 55 dias e foram eutanasiados no 120º dia de experimento. Outros três caprinos constituíram o grupo controle (Grupo IV). Nos grupos experimentais, as lesões encefálicas foram avaliadas por histopatologia e adicionalmente avaliaram-se as lesões cerebelares por morfometria, mediante mensuração da espessura da camada molecular, do número de neurônios de Purkinje e da área dos corpos celulares dessas células. Os principais sinais clínicos e lesões microscópicas foram semelhantes aos previamente reportados em animais intoxicados por plantas que contem swainsonina. Nos caprinos do GII e GIII, os primeiros sinais clínicos foram observados entre o 22º e 29º dia de experimento; clinicamente a doença desenvolvida por esses animais foi semelhante aos casos espontâneos. Nenhum dos caprinos do GIII se recuperou dos sinais neurológicos. Esse resultado evidencia que o consumo da planta por 26-28 dias após a observação dos primeiros sinais clínicos é suficiente para provocar lesões irreversíveis. Pela análise morfométrica, a camada molecular do cerebelo dos caprinos do Grupo I e III eram mais delgadas que às dos caprinos do grupo controle, e os neurônios de Purkinje estavam atróficos. Sugere-se que essas alterações sejam responsáveis pelo quadro clínico neurológico observado nos caprinos que deixam de ingerir a planta e apresentam seqüelas da intoxicação.

Ocular Abnormality of Korean Patients with Molecular Genetically Confirmed Gaucher Disease

PURPOSE: To investigate the ophthalmologic manifestations of Korean patients with Gaucher disease. METHODS: Clinical records of 5 patients who were referred to the pediatric ophthalmology clinic of Seoul National University Bundang Hospital after diagnosis of Gaucher disease at the genetics clinic of Ajou University Hospital between 2007 and 2008 were retrospectively reviewed. RESULTS: Five patients with type 3 Gaucher disease had hepatosplenomegaly and oculomotor apraxia, and 4 patients had growth and developmental delay. The most commonly detected genetic mutation was L444P. In addition, P201H, F2131, R257Q, and D315E+Rec 1b were identified. Five patients had oculomotor apraxia and limitation of abduction, and 4 patients had esotropia. One of the 4 patients who showed combined limitation of abduction, oculomotor apraxia, and esotropia, yet did not have growth and developmental delay. CONCLUSIONS: Most of the patients who were referred for ocular motor abnormalities with Gaucher disease showed a limitation of abduction, oculomotor apraxia, and esotropia. In patients with a limitation of abduction, oculomotor apraxia, and esotropia, Gaucher disease should be considered. Ophthalmologic examination is essential for subtyping and prognosing Gaucher disease.

Enfermedad de Gaucher en Latinoamérica: Un informe del Registro Internacional y del Grupo Latinoamericano para la Enfermedad de Gaucher / Gaucher disease in Latin America: A report from the Gaucher Disease International Registry and the Latin Americam Group for Gaucher Disease

La enfermedad de Gaucher, por su escasa frecuencia, está incluida dentro de las llamadas enfermedades huérfanas. En 1991 se creó el Registro Internacional de Gaucher y en 1992 se incorporaron los primeros pacientes de Latinoamérica. En el año 2008 se creó el Grupo Latinoamericano para la Enfermedad de Gaucher (GLAEG) cuyos principales objetivos son fomentar la realización de consensos regionales, difundir el ingreso de pacientes al registro internacional y aumentar el conocimiento sobre la enfermedad para lograr mejorar la atención y la calidad de vida de los pacientes. Hasta abril del 2010 ingresaron 5828 pacientes de todo el mundo, 911 (15.6%) son de Latinoamérica. Este es el primer informe global de la enfermedad en la Región: hay un predominio del sexo femenino, la forma clínica más frecuente es el tipo I (95%); al diagnóstico la mayoría son <20 años (68%). Las manifestaciones clínicas más frecuentes al diagnóstico son esplenomegalia (96%) y anemia (49%), el 80% presentó hallazgos radiológicos de compromiso óseo. En nuestra Región, la gran mayoría de los pacientes (89%) ha recibido alguna vez terapia de reemplazo enzimática con imiglucerasa logrando, con un seguimiento prolongado (hasta10 años), las metas terapéuticas que muestran la gran eficacia de la terapia. Si bien el porcentaje de pacientes con terapia es alto, las suspensiones de tratamiento son frecuentes. Las principales deficiencias en nuestra Región son: la carencia de evaluaciones viscerales volumétricas, de densitometría y de estudios moleculares en algunos pacientes. El principal problema es el subdiagnóstico.

Gaucher disease -due to its low frequency- is considered an orphan disease. In 1991 the International Gaucher Registry was created and in 1992 the first patients from Latin America were enrolled. In 2008 the Latin American Group for Gaucher Disease was initiated. Its main objectives are to promote regional consensus, to stimulate the enrolment of patients into the International Gaucher Registry and the enhancement of knowledge on this disease, and to achieve better care and quality of life of patients in our Region. Until April 2010, 5828 patients have been enrolled all around the world, 911 (15.6%) from Latin America. This is the first comprehensive report of the disease in the Region. In our population there is a predominance of females, the most common clinical form is the type I (95%) and the age at diagnosis is before 20 years in 68% of patients. The most frequent clinical manifestations at diagnosis are splenomegaly (96%) and anemia (49%). Eighty percent of patients had radiographic findings of bone involvement. In our Region, the vast majority of patients (89%) had received enzyme replacement therapy with imiglucerase; with a long follow-up (up to 10 years) they have achieved the therapeutic goals, showing the great effectiveness of therapy. While the percentage of patients with therapy is high, discontinuations are common. The main deficiencies in our Region are: the lack of visceral volumetric evaluations and densitometries as well as molecular analysis for some patients. The main problem is the under-diagnosis of patients.

Pathological findings in fetuses of goats and cattle poisoned by Sida carpinifolia (Malvaceae) / Achados patológicos em fetos de caprinos e bovinos intoxicados por Sida carpinifolia (Malvaceae)

In Brazil, the consumption of Sida carpinifolia by livestock has been associated with neurological diseases linked to lysosomal storage disorders. This paper describes the pathological findings in two caprine fetuses from dams that were experimentally poisoned with S. carpinifolia. The goats were orally dosed with 10 and 13g/kg of a paste of green chopped S. carpinifolia for 30 days and were observed for an additional 15 days period after the last dosage with the plant; thereafter they were euthanized and necropsied. The dams showed only slight clinical signs. The study also includes the findings in one bovine fetus from a naturally S. carpinifolia poisoned cow which showed mild incoordination, generalized tremors, staggering, and frequent falls. The cow was euthanized and necropsied. While there were no significant histopathological changes in the goats, in the cow vacuolation of Purkinje neurons of the cerebellum, pancreatic acinar cells, and thyroid follicular cells were observed. The main microscopic changes observed in the caprine and bovine fetuses were vacuolation in the epithelium of renal tubules, thyroid follicular cells, and Purkinje neurons of the cerebellum. Transmission electron microscopy of sections from CNS of the cow and its fetus revealed vacuoles containing fine granular material surrounded by membrane. Lectin-histochemistry of CNS sections from goat fetuses marked lightly to sWGA lectins, WGA, and Con-A.

No Brasil, o consumo de Sida carpinifolia por animais de produção tem sido associada a doenças neurológicas relacionadas com doença de depósito lisossômico. Este trabalho descreve os achados patológicos observados em dois fetos caprinos de mães que foram experimentalmente intoxicadas por S. carpinifolia. As cabras foram intoxicadas experimentalmente com S. carpinifolia nas doses de 10 e 13g/kg durante 30 dias e foram acompanhadas durante 15 dias após o consumo da planta. Após este período foram eutanasiadas e necropsiadas. O estudo também inclui os achados patológicos encontrados em um feto de uma fêmea bovina intoxicada naturalmente pela planta, que mostrou leve incoordenação, tremores generalizados, andar desequilibrado e quedas frequentes. A vaca foi eutanasiada e necropsiada. Embora não houvesse alterações histológicas significativas nas cabras, vacuolização dos neurônios de Purkinje do cerebelo, das células acinares do pâncreas e nas células foliculares da tireoide foram observadas na vaca. As principais alterações histológicas observadas nos fetos caprinos e no feto bovino foram vacuolização no epitélio dos túbulos renais, nas células foliculares da tireoide e nos neurônios de Purkinje do cerebelo. Na microscopia eletrônica de transmissão do sistema nervoso central da vaca e de seu feto revelaram-se vacúolos contendo material finamente granulado e delimitado por membrana. Na técnica de lectina-histoquímica dos fetos caprinos houve marcação leve no SNC para as lectinas sWGA, WGA e para Con-A.