Calidad de vida en pacientes con enfermedad de Pompe: estudio observacional / Quality of Life in Patients with Pompe Disease: Cross-Sectional Study

Introducción: La enfermedad de Pompe es una enfermedad genética multisistémica y rápidamente progresiva, que causa compromiso muscular (esquelético, cardíaco y liso), severa hipotonía y dificultad en la deglución. Debido a la naturaleza de la enfermedad, la calidad de vida de las personas que la padecen puede verse más afectada con respecto a la población general. Método: Se llevó a cabo un estudio descriptivo de corte transversal. Se diseñó un instrumento tipo encuesta con preguntas de caracterización sociodemográfica y referentes a la enfermedad. Para medir la calidad de vida se aplicó el Medical Outcomes Study 36-Item Short Form (SF-36) Questionnaire. Se hizo una comparación entre grupos, con nivel de significancia de 0,05. Resultados: Se obtuvieron encuestas de 27 pacientes de seis países. La edad media fue de 40,52 años, el 59 % fueron mujeres, el 51 % casados, el 63 % activos laboralmente, con edad media de diagnóstico de 30,3 años (SD = 15,557). La dimensión con menor media fue el rol físico (10,2; IC 95 % = 1,5-21,9), mientras que la de mayor media fue la salud mental (65,5; IC 95 % = 56,9-74,0). El 29,7 % (IC 95 % = 11,2-48,0) de los encuestados consideró sentirse en peores condiciones de salud que el año anterior. Discusión: Se evidencia una baja calidad de vida en pacientes con EP, en comparación con la población general, si se tienen en cuenta otros estudios que utilizan el mismo cuestionario. Conclusiones: Se evidencia una baja calidad de vida en los pacientes con enfermedad de Pompe participantes; las dimensiones asociadas con parámetros físicos fueron las de menores puntuaciones.

Introduction: Pompe disease is a rapidly progressive, multisystemic genetic disease that causes muscle involvement (skeletal, cardiac and smooth), severe hypotonia and difficulty in swallowing. Due to the nature of the disease, the quality of life may be more affected compared to the general population. Method: A descriptive cross-sectional study was carried out. A survey-type instrument was designed with questions of sociodemographic characterization and those referring to the disease. To measure Quality of Life, the Medical Outcomes Study 36-Item Short Form (SF-36) questionnaire was applied. A comparison was made between groups with a significance level of 0,05. Results: 27 surveys of patients from six countries were obtained. The mean age 40.52 years, women 59 %, married 51 %, 63 % active in employment, with a mean age of diagnosis of 30.3 years (SD = 15,557). The dimension with the lowest mean was the Physical Role (10.2; 95 % CI = 1.5 - 21.9), while the one with the highest mean was the Mental Health dimension (65.5; 95 % CI = 56.9 - 74.0). 29.7 % (95 % CI = 11.2 - 48.0) of those surveyed considered they felt in worse health conditions than the previous year. Discussion: Low quality of life is evidenced in patients with PD in comparison to the general population described in other studies using the same questionnaire. Conclusions: A low quality of life is evidenced in the study individuals where the dimensions related to the physical area were lower.

Tratamiento de la enfermedad de Pompe

Introducción: La enfermedad de Pompe es un trastorno de origen genético causado por la deficiencia de la enzima alfa-glucosidasa ácida, que se caracteriza por el acumulo anormal de glucógeno en los músculos y otros tejidos, generando una debilidad muscular progresiva, la cual debe ser diagnosticada y tratada de forma oportuna, ya que de esto dependerá el pronóstico, la sobrevida y la funcionalidad de los pacientes con esta condición. Contenidos: El abordaje multidisciplinario incluye tanto una adecuada valoración y soporte nutricional como el inicio del tratamiento modificador de enfermedad a través de la terapia de reemplazo enzimático, que a su vez dependerá de la forma de presentación, la variante genética, el perfil inicial del paciente, las condiciones especiales que puedan existir y las metas propias para cada paciente. Para garantizar un manejo adecuado, se deben realizar estudios de seguimiento con parámetros objetivos, evaluar posibles eventos secundarios e instaurar su manejo en caso de presentarlos. Conclusiones: El pronóstico de esta enfermedad dependerá del inicio oportuno del tratamiento, la implementación de pautas nutricionales adecuadas y el establecimiento del seguimiento de los parámetros clínicos y paraclínicos para cada uno de los pacientes.

Introduction: Pompe disease is a disorder of genetic origin caused by the deficiency of the acid alpha-glucosidase enzyme, which is characterized by the abnormal accumulation of glycogen in the muscles and other tissues, generating progressive muscle weakness, which must be diagnosed and treated in a timely manner, since the prognosis, survival, and functionality of patients with this condition will depend on this. Contents: The multidisciplinary approach includes both an adequate evaluation and nutritional support as well as the initiation of disease-modifying treatment through enzyme replacement therapy, which in turn will depend on the form of presentation, the genetic variant, the initial profile of the patient, the special conditions that may exist and the specific goals for each patient. To guarantee adequate management, follow-up studies must be carried out with objective parameters, evaluate possible secondary events and establish their management in case of presenting them. Conclusions: The prognosis of this disease will depend on the timely initiation of treatment, the implementation of adequate nutritional guidelines and the establishment of monitoring of clinical and paraclinical parameters for each of the patients.

Rehabilitación en la enfermedad de Pompe

Introducción: Gracias a la nueva herramienta de tratamiento con la terapia de reemplazo enzimático en la enfermedad de Pompe, se ha reducido la mortalidad a corto plazo. Contenidos: Esta herramienta permite a los pacientes mantener la independencia funcional y la adaptación de las habilidades motrices para su participación en varios aspectos de la vida diaria. Conclusiones: El abordaje de estos pacientes debe ser multidisciplinario, para dar un manejo integral a la condición clínica de cada individuo, y procurar el tratamiento de los sistemas físicos y emocionales que se pueden ver alterados con el curso de la enfermedad: osteomuscular, cardiovascular y respiratorio, deglución, lenguaje, nutrición y psicológico, incluidos los cuidados paliativos y el manejo del dolor.

Introduction: Enzyme replacement therapy in Pompe disease reduces short-term mortality. Contents: This therapy allows patients to maintain functional independence and adaptation of motor skills for patient participation in various aspects of daily life. Conclusions: The approach with this patients should be multidisciplinary to provide comprehensive management of the clinical condition of each individual seeking treatment of the physical and emotional aspects that may be altered in the disease progression: musculoskeletal, cardiovascular, respiratory, swallowing, language, nutritional and psychological; also including palliative care and pain management.

Splicing abnormalities caused by a novel mutation in the PHKA2 gene in children with glycogen storage disease type IX / 中华肝脏病杂志

Objective: Glycogen storage disease type IX (GSD-IX) is a rare primary glucose metabolism abnormality caused by phosphorylase kinase deficiency and a series of pathogenic gene mutations. The clinical characteristics, gene analysis, and functional verification of a mutation in a child with hepatomegaly are summarized here to clarify the pathogenic cause of the disease. Methods: The clinical data of a child with GSD-IX was collected. Peripheral blood from the child and his parents was collected for genomic DNA extraction. The patient's gene diagnosis was performed by second-generation sequencing. The suspected mutations were verified by Sanger sequencing and bioinformatics analysis. The suspected splicing mutations were verified in vivo by RT-PCR and first-generation sequencing. Results: Hepatomegaly, transaminitis, and hypertriglyceridemia were present in children. Liver biopsy pathological examination results indicated glycogen storage disease. Gene sequencing revealed that the child had a c.285 + 2_285 + 5delTAGG hemizygous mutation in the PHKA2 gene. Sanger sequencing verification showed that the mother of the child was heterozygous and the father of the child was of the wild type. Software such as HSF3.1 and ESEfinder predicted that the gene mutation affected splicing. RT-PCR of peripheral blood from children and his mother confirmed that the mutation had caused the skipping of exon 3 during the constitutive splicing of the PHKA2 gene. Conclusion: The hemizygous mutation in the PHKA2 gene (c.285 + 2_285 + 5delTAGG) is the pathogenic cause of the patient's disease. The detection of the novel mutation site enriches the mutation spectrum of the PHKA2 gene and serves as a basis for the family's genetic counseling.

A case of glycogen storage disease type Ⅰa with gout as the first manifestation / 浙江大学学报·医学版

A 24-year-old male was admitted due to recurrent redness, swelling, fever and pain in the ankle, frequently accompanied by hungry feeling. Dual energy CT scans showed multiple small gouty stones in the posterior edge of the bilateral calcaneus and in the space between the bilateral metatarsophalangeal joints. The laboratory examination results indicated hyperlipidemia, high lactate lipids, and low fasting blood glucose. Histopathology of liver biopsy showed significant glycogen accumulation. The results of gene sequencing revealed the compound heterozygous mutations of the G6PC gene c.248G>A (p.Arg83His) and c.238T>A (p.Phe80Ile) in the proband. The c.248G>A mutation was from mother and the c.238T>A mutation was from father. The diagnosis of glycogen storage disease type Ⅰa was confirmed. After giving a high starch diet and limiting monosaccharide intake, as well as receiving uric acid and blood lipids lowering therapy, the condition of the patient was gradually stabilized. After a one-year follow-up, there were no acute episodes of gout and a significant improvement in hungry feeling in the patient.

Research progress of nervous system damage in Pompe disease / 中国当代儿科杂志

Pompe disease, also known as glycogen storage disease type Ⅱ, is a rare autosomal recessive disease. With the application of enzyme replacement therapy, more and more patients with Pompe disease can survive to adulthood, and nervous system-related clinical manifestations gradually emerge. Nervous system involvement seriously affects the quality of life of patients with Pompe disease, and a systematic understanding of the clinical manifestations, imaging features and pathological changes of nervous system injury in Pompe disease is of great significance for the early identification and intervention of Pompe disease. This article reviews the research progress of neurological damage in Pompe disease.

Acometimento do Ventrículo Direito na Cardiomiopatia por Depósito de Glicogênio (PRKAG2): Análise Ecocardiográfica Convencional e Avançada / Right Ventricle Involvement by Glycogen Storage Cardiomyopathy (PRKAG2): Standard and Advanced Echocardiography Analyses

Resumo Fundamento A síndrome do PRKAG2 é uma doença hereditária autossômica dominante rara, de início precoce. Objetivamos descrever os achados ecocardiográficos do ventrículo direito (VD) usando modalidades bi e tridimensionais (2D e 3D), incluindo índices de deformação miocárdica nesta cardiomiopatia. Também objetivamos demonstrar se esta técnica poderia identificar alterações na função do VD que pudessem distinguir quaisquer achados particulares. Métodos Trinta pacientes com síndrome do PRKAG2 (R302Q e H401Q) geneticamente comprovada, 16 (53,3%) do sexo masculino, com idade média de 39,1 ± 15,4 anos, foram submetidos a exame ecocardiográfico completo. A visão de 4 câmaras com foco no VD foi adquirida para medições 2D e 3D. Os testes t de Student ou Wilcoxon-Mann-Whitney foram usados para comparar as variáveis numéricas entre 2 grupos, e p < 0,05 foi considerado significativo. Resultados Doze pacientes (40%) tiveram marca-passo implantado por 12,4 ± 9,9 anos. A espessura diastólica média da parede livre do VD foi de 7,9 ± 2,9 mm. O strain longitudinal de 4 câmaras do VD (SL4VD), incluindo a parede livre e o septo interventricular, foi de -17,3% ± 6,7%, e o strain longitudinal da parede livre do VD (SLPLVD) foi de −19,1% ± 8,5%. A razão apical do SLPLVD mediu 0,63 ± 0,15. A fração de ejeção (FE) 3D média do VD foi de 42,6% ± 10,9% e abaixo dos limites normais em 56,7% dos pacientes. Correlação positiva ocorreu entre FE 3D do VD, SL4VD e SLPLVD, principalmente para pacientes sem marca-passo (p = 0,006). Conclusão O envolvimento do VD em PRKAG2 é frequente e ocorre em diferentes graus. A ecocardiografia é uma ferramenta valiosa na detecção de anormalidades miocárdicas do VD nesta condição. O uso de SL4VD 2D, SLPLVD e FE 3D oferecem indicadores confiáveis de disfunção sistólica do VD nesta cardiomiopatia rara e desafiadora.

Abstract Background PRKAG2 syndrome is a rare, early-onset autosomal dominant inherited disease. We aimed to describe the right ventricle (RV) echocardiographic findings using two and three-dimensional (2D and 3D) modalities including myocardial deformation indices in this cardiomyopathy. We also aimed to demonstrate whether this technique could identify changes in RV function that could distinguish any particular findings. Methods Thirty patients with genetically proven PRKAG2 (R302Q and H401Q), 16 (53.3%) males, mean age 39.1 ± 15.4 years, underwent complete echocardiography examination. RV-focused, 4-chamber view was acquired for 2D and 3D measurements. Student's t or Wilcoxon-Mann-Whitney tests were used to compare numerical variables between 2 groups, and p < 0.05 was considered significant. Results Twelve patients (40%) had a pacemaker implanted for 12.4 ± 9.9 years. RV free wall mean diastolic thickness was 7.9 ± 2.9 mm. RV 4-chamber longitudinal strain (RV4LS), including the free wall and interventricular septum, was -17.3% ± 6.7%, and RV free wall longitudinal strain (RVFWLS) was −19.1% ± 8.5%. The RVFWLS apical ratio measured 0.63 ± 0.15. Mean RV 3D ejection fraction (EF) was 42.6% ± 10.9% and below normal limits in 56.7% of patients. Positive correlation occurred between RV 3DEF, RV4LS, and RVFWLS, especially for patients without a pacemaker (p = 0.006). Conclusion RV involvement in PRKAG2 syndrome is frequent, occurring in different degrees. Echocardiography is a valuable tool in detecting RV myocardial abnormalities in this condition. The use of 2D RV4LS, RVFWLS, and 3DEF offers reliable indicators of RV systolic dysfunction in this rare, challenging cardiomyopathy.

Flutter Atrial na Síndrome do PRKAG2: Características Clínicas e Eletrofisiológicas / Atrial Flutter in PRKAG2 Syndrome: Clinical and Electrophysiological Characteristics

Resumo Fundamento A síndrome do PRKAG2 é uma rara doença genética autossômico dominante, fenocópia da miocardiopatia hipertrófica, caracterizada pelo acúmulo intracelular de glicogênio. Manifestações clínicas incluem pré-excitação ventricular, hipertrofia ventricular, distúrbio de condução cardíaca e arritmias atriais. Objetivo Comparar características clínicas e eletrofisiológicas observadas em pacientes com flutter atrial, com e sem síndrome do PRKAG2. Métodos Estudo observacional, comparativo de pacientes com flutter atrial: grupo A, cinco pacientes de família com síndrome do PRKAG2; e grupo B, 25 pacientes sem fenótipo da síndrome. O nível de significância foi de 5%. Resultados Todos os pacientes do grupo A apresentaram pré-excitação ventricular e bloqueio de ramo direito; quatro tinham marca-passo (80%). Pacientes do grupo A tinham menor idade (39±5,4 vs. 58,6±17,6 anos, p=0,021), e maior espessura de septo interventricular (mediana=18 vs. 10 mm; p<0,001) e parede posterior (mediana=14 vs. 10 mm; p=0,001). Quatro do grupo A foram submetidos a estudo eletrofisiológico, sendo observada via acessória fascículo-ventricular; em três foi realizada ablação do flutter atrial. Todos os do grupo B foram submetidos à ablação do flutter atrial, sem evidência de via acessória. Observado maior prevalência no grupo B de hipertensão arterial, diabetes mellitus, doença coronariana e apneia do sono, sem diferença estatisticamente significante. Conclusão Portadores da síndrome do PRKAG2 apresentaram flutter atrial em idade mais precoce, e menos comorbidades, quando comparados a pacientes com flutter atrial sem fenótipo da mutação. Importante suspeitar de miocardiopatia geneticamente determinada, como síndrome do PRKAG2, em jovens com flutter atrial, especialmente na presença de pré-excitação ventricular e hipertrofia ventricular familiar.

Abstract Background PRKAG2 syndrome is a rare autosomal dominant disease, a phenocopy of hypertrophic cardiomyopathy characterized by intracellular glycogen accumulation. Clinical manifestations include ventricular preexcitation, cardiac conduction disorder, ventricular hypertrophy, and atrial arrhythmias. Objective To compare the clinical and electrophysiological characteristics observed in patients with atrial flutter, with and without PRKAG2 syndrome. Methods An observational study comparing patients with atrial flutter: group A consisted of five patients with PRKAG2 syndrome from a family, and group B consisted of 25 patients without phenotype of PRKAG2 syndrome. The level of significance was 5%. Results All patients in group A had ventricular preexcitation and right branch block, and four had pacemakers (80%). Patients in group A were younger (39±5.4 vs 58.6±17.6 years, p=0.021), had greater interventricular septum (median=18 vs 10 mm; p<0.001) and posterior wall thickness (median=14 vs 10 mm; p=0.001). In group A, four patients were submitted to an electrophysiological study, showing a fasciculoventricular pathway, and atrial flutter ablation was performed in tree. All patients in group B were submitted to ablation of atrial flutter, with no evidence of accessory pathway. Group B had a higher prevalence of hypertension, diabetes mellitus, coronary artery disease and sleep apnea, with no statistically significant difference. Conclusion Patients with PRKAG2 syndrome presented atrial flutter at an earlier age and had fewer comorbidities when compared to patients with atrial flutter without mutation phenotype. The occurrence of atrial flutter in young individuals, especially in the presence of ventricular preexcitation and familial ventricular hypertrophy, should raise the suspicion of PRKAG2 syndrome.

Gastrointestinal characteristics of glycogen storage disease type Ⅰ in children / 中华实用儿科临床杂志

Objective:To investigate the gastrointestinal characteristics of children with glycogen storage disease (GSD) type Ⅰ.Methods:From June to December 2020, clinical data of children aged 0-18 years with GSD type Ⅰ diagnosed by genetic testing from all provinces and cities in China, including Beijing, Shanghai, Guangdong, Guangxi, Hunan, Sichuan, Yunnan, Guizhou, Henan, Hebei, Zhejiang, Jiangsu, Shaanxi, Anhui and Heilongjiang, were collected.A cross-sectional questionnaire survey was used for data analysis.Results:A total of 52 questionnaires were obtained, and 43 eligible patients aged 1-18 years were recruited, involving 30 males (69.8%) and 13 females (30.2%). Among them, 9 patients were GSD type Ⅰa and 34 patients were type Ⅰb.Seven patients (16.3%) had siblings who were also diagnosed as GSD type Ⅰb.The gastrointestinal manifestations included recurrent diarrhea in 26 patients (60.5%), perianal lesions (erythema, ulcer, abscess) in 25 patients (58.1%), abdominal pain/distension in 24 patients (55.8%), nausea/vomiting in 22 patients (51.1%), mucus/bloody stool in 14 patients (32.6%). Thirty-three patients (76.7%) had recurrent stomatitis and oral ulcer, and 38 patients (88.0%) had at least two gastrointestinal symptoms.White blood cell (WBC) count was <4.0×10 9/L in 24 patients (55.8%), and absolute neutrophils count was <1.5×10 9/L in 19 patients (44.2%), which was <0.5×10 9/L in 10 patients (23.3%). WBC count and absolute neutrophils count both decreased in children with GSD type Ⅰb.Platelets were >300×10 9/L in 30 patients (69.8%). Eighteen patients with GSD type Ⅰb underwent gastroscopy and colonoscopy, and 16 patients were diagnosed with GSD-related inflammatory bowel disease.Thirty-nine patients (90.7%) were fed with raw corn starch, 3 patients (6.9%) with maltodextrin and 19 patients (44.2%) with special enteral formula.Twenty patients with type Ⅰb GSD needed repeated antibiotic treatment due to neutropenia and neutrophil dysfunction.Fifteen patients were treated with granulocyte colony-stimulating factor (G-CSF). Among them, 11 patients were diagnosed as GSD-related bowel disease. Conclusions:Children with GSD type Ⅰ commonly have gastrointestinal symptoms, especially those with GSD type Ⅰb.The incidence of GSD-related inflammatory bowel disease is high in those children.G-CSF treatment cannot prevent the development of GSD-associated inflammatory bowel disease and its pathogenesis needs further research.Diet therapy is the first-line treatment of GSD type Ⅰ.Multidisciplinary management is helpful to reduce the complications and improve the quality of life in children with GSD type Ⅰ.

Clinical characteristics and gene analysis of one case of glycogen storage disease type Ⅱ / 中国基层医药

Objective:To investigate the key points of diagnosis and treatment of glycogen storage disease type Ⅱ(GSD Ⅱ).Methods:The clinical data of one child patient with GSD Ⅱ who received treatment in Hainan Children's Hospital on May 7, 2017 were retrospectively analyzed.Results:The child presented with atypical clinical manifestations, including pneumonia first, accompanied by muscle weakness and elevated muscle enzymes. Whole-genome sequencing showed that there were two heterozygous mutations in the acid alpha-glucosidase (GAA) gene, c.871C > T and c.1447G > A. The child was diagnosed with GSD Ⅱ.Conclusion:GSD Ⅱ has atypical clinical manifestations. It is easily misdiagnosed. Early whole-genome sequencing is helpful for the diagnosis of GSD Ⅱ.

Clinical and pathological features of children with glycogen storage disease: An analysis of 10 cases / 临床肝胆病杂志

Objective To investigate the clinical and pathological features of children with glycogen storage disease (GSD). Methods A retrospective analysis was performed for ten children with GSD who were admitted to the Third Hospital of Hebei Medical University and The Fifth Medical Center of Chinese PLA General Hospital from January 2002 to January 2022, based on medical history, liver biochemistry, and liver biopsy, and population characteristics, clinical manifestations, biochemical parameters, and liver histopathological characteristics were compared and analyzed. Results All ten children had developmental retardation and a short stature, with the manifestations of abnormal liver function, mild weakness, poor appetite, yellow urine, and yellow eyes, and four children had hepatosplenomegaly. Among the ten children, six had the clinical manifestations of hypoglycemia, and one had bilateral gastrocnemius hypertrophy and positive Gower sign. Two children had positive CMV IgG. Liver histopathological manifestations included diffuse enlargement of hepatocytes, light cytoplasm, and small nucleus in the middle like plant cells, with or without fibrous tissue proliferation. Conclusion Most patients with GSD have developmental retardation and abnormal aminotransferases, and liver pathological examination shows specific pathological features.

Reacciones de hipersensibilidad a alglucosidasa alfa en enfermedad de Pompe: dos casos de desensibilización exitosa / Hypersensitivity reactions to alglucosidase alfa in Pompe disease: two cases of successful desensitization

La enfermedad de Pompe es un desorden neuromuscular autosómico recesivo de baja prevalencia, causado por la deficiencia total o parcial de la enzima alfa glucosidasa ácida (GAA), cuya única terapia de reemplazo enzimático disponible es la alglucosidasa alfa recombinante. Las reacciones adversas asociadas a la infusión se presentan con frecuencia. Se reportan dos casos de desensibilización exitosa con alglucosidasa alfa utilizando protocolos con dosis meta de 20 mg/kg, administrados quincenalmente; el primero de ellos, en una niña con historia de reacción adversa grave a los 15 meses de edad, en quien se utilizó un esquema con una dilución inicial de 1/10.000.000 de 28 pasos y una duración total de 13,1 horas. En el segundo caso, la paciente tuvo una reacción adversa grave a los 4 años de edad, se utilizó el protocolo de 22 pasos, concentración inicial de 1/1.000.000 y duración total de 7,2 horas. Se concluye que en pacientes con enfermedad de Pompe que presentan reacciones adversas durante la terapia de reemplazo enzimático, es posible realizar la desensibilización cada dos semanas con la dosis estándar de 20 mg/kg de forma exitosa, y progresivamente lograr la administración usual de la infusión

Pompe disease is a low prevalence autosomal recessive neuromuscular disorder, caused by total or partial deficiency of the acid alpha-glucosidase (GAA) enzyme, and its only available enzyme replacement therapy is the recombinant alglucosidase alfa. Infusion-associated adverse reactions occur frequently. Two cases of successful desensitization with alglucosidase alfa using protocols with a target dose of 20 mg/kg administered biweekly are reported; the first was a girl who had a history of serious adverse reaction at the age of 15 months, and undergone to a scheme with an initial dilution of 1/10,000,000 with 28 steps and a total duration of 13.1 hours. In the second case, the patient had a severe adverse reaction at the age of 4 years, a 22-step protocol was used with an initial concentration of 1/1,000,000 and a total duration of 7.2 hours. In conclusion, in patients with Pompe disease who presented adverse reactions during enzyme replacement therapy with alglucosidase alfa, it is possible to perform desensitization every two weeks with the standard dose of 20 mg/kg, and progressively achieve the usual administration of the infusion

Manejo em longo prazo de glicogenose tipo 1b: experiência de um centro terciário brasileiro / Long term management of glycogen storage disease type 1b: a brazilian tertiary center experience

ABSTRACT BACKGROUND Glycogen storage disease (GSD) type 1b is a multisystemic disease in which immune and infectious complications are present, in addition to the well-known metabolic manifestations of GSD. Treatment with granulocyte-colony stimulating factor (G-CSF) is often indicated in the management of neutropenia and inflammatory bowel disease. OBJECTIVE To report on the demographics, genotype, clinical presentation, management, and complications of pediatric patients with glycogen storage disease type 1b (GSD 1b), with special attention to immune-related complications. METHODS Retrospective case series of seven patients with GSD 1b diagnosed and followed at a tertiary university hospital in Brazil, from July/2000 until July/2016. RESULTS Mean age at referral was fourteen months. Diagnosis of GSD 1b was based on clinical and laboratory findings and supported by genetic studies in five cases. All patients presented suffered from neutropenia, managed with G-CSF - specifically Filgrastim. Hospitalizations for infections were frequent. Two patients developed inflammatory bowel disease. Six patients remained alive, one died at age 14 years and 9 months. The mean age at the end of the follow-up was 11.5 years. Compliance to treatment was suboptimal: poor compliance to medications, starch and dietetic management of GSD were documented, and outpatient appointments were frequently missed. CONCLUSION Managing GSD 1b is challenging not only for the chronic and multisystemic nature of this disease, but also for the additional demands related dietary restrictions, use of multiple medications and the need for frequent follow-up visits; furthermore in Brazil, the difficulties are increased in a scenario where we frequently care for patients with unfavorable socioeconomic status and with irregular supply of medications in the public health system.

RESUMO CONTEXTO Glicogenose (GSD) tipo 1b é uma doença multissistêmica em que complicações imunológicas e infecciosas estão presentes, além das manifestações metabólicas bem conhecidas da GSD. O tratamento com fator estimulador de colônias de granulócitos (G-CSF) é frequentemente indicado no tratamento da neutropenia e doença inflamatória intestinal. OBJETIVO Relatar sobre a dados demográficos, genótipo, apresentação clínica, manejo e complicações de pacientes pediátricos com GSD tipo 1b (GSD 1b), com atenção especial às complicações relacionadas ao sistema imunológico. MÉTODOS Série de casos retrospectiva de sete pacientes com GSD 1b diagnosticados e acompanhados em um hospital universitário terciário no Brasil, de julho/2000 a julho/2016. RESULTADOS A idade média no encaminhamento foi de 14 meses. O diagnóstico de GSD 1b foi baseado em achados clínicos e laboratoriais e apoiado por estudos genéticos em cinco casos. Todos os pacientes apresentaram neutropenia, tratada com G-CSF - especificamente Filgrastim. As hospitalizações por infecções foram frequentes. Dois pacientes desenvolveram doença inflamatória intestinal. Seis pacientes permanecem vivos, um morreu aos 14 anos e 9 meses de idade. A média de idade ao final do acompanhamento foi de 11,5 anos. A adesão ao tratamento foi sub-ótima: má adesão aos medicamentos, amido e manejo dietético de GSD foram documentados, e consultas ambulatoriais foram frequentemente perdidas. CONCLUSÃO O manejo da GSD 1b é um desafio, não apenas pela natureza crônica e multissistêmica desta doença, mas também pelas demandas adicionais relacionadas a restrições dietéticas, uso de múltiplos medicamentos e a necessidade de consultas de acompanhamento frequentes; no Brasil, isso ainda é dificultado em um cenário em que frequentemente atendemos pacientes com situação socioeconômica desfavorável e com oferta irregular de medicamentos no sistema público de saúde.

Effect observation and literature review of enzyme replacement therapy in late-onset Pompe disease / 中华神经科杂志

Objective:To analyze the efficacy and safety of enzyme therapy in late-onset Pompe disease (LOPD) patients, so as to provide reference for the treatment and prognosis of LOPD.Methods:The effect of α-glucosidase (GAA) on a patient diagnosed with LOPD in the Affiliated Hospital of Jining Medical University was observed and analyzed. Besides, literature related to enzyme therapy in LOPD patients were searched in PubMed, Web of Science, Medline databases. Twenty-one studies containing clinical data from 910 LOPD patients related to enzyme therapy were finally included for analysis.Results:The patient developed muscle weakness since he was 16 years old. The GAA activity in peripheral blood was 0. Electromyography suggested myogenic lesions in both lower extremities. Compound heterozygous mutations of GAA gene were found by next- generation sequencing. Muscle biopsy revealed characteristic vacuolar changes. After eight years of diagnosis, the patient was given enzyme therapy for 18.5 months, 20 times in total. The symptoms of muscle weakness were slightly improved in the early stages of treatment without obvious adverse reactions. Most of the 910 LOPD patients were stabilized or had improved muscular and (or) respiratory function following treatment with GAA.Conclusion:GAA treatment is effective and well tolerated. In patients with advanced severe LOPD, enzyme replacement therapy remains effective even years after onset.

Dietary management of one child with glycogen storage disease type I and severe hyperlipidemia / 中国实用护理杂志

Objective:To summarizes the diet management of one child with GSD I and severe hyperlipidemia.Methods:Key points of diet management include: making an individual diet plan, correcting parents' dietary misunderstanding, adjusting dietary and keeping following up regularly and keeping a food diary.Results:Following up for 11 months, the children basically formed a stable diet pattern, the blood glucose level was basically maintained between 4~6 mmol/L, the indicators of hyperlipidemia, hyperlactic acid and liver function were significantly improved compared with the previous period, and the height increase was guaranteed, while the weight gain was effectively controlled.Conclusions:It shows that individualized dietary guidance has a significant effect on the maintenance of blood glucose level, improvement of growth and development status and metabolic control in children with GSD I.

Clinical and genetic features of patients with glycogen storage disease type Ⅸa: An analysis of 20 cases / 临床肝胆病杂志

ObjectiveTo investigate the clinical and genetic features of patients with glycogen storage disease type Ⅸa (GSD Ⅸa), and to improve the clinical understanding of the disease. MethodsA retrospective analysis was performed for the clinical data of 20 patients who were hospitalized and genetically diagnosed with GSD Ⅸa in Children’s Hospital of Fudan University from January 2015 to December 2018, and their clinical and genetic features were summarized. ResultsAll 20 patients with GSD Ⅸa were male, with a median age of 2.5 years at the time of confirmed diagnosis. All patients had hepatomegaly and elevated aminotransferases; of all patients, there were 5 patients (250%) with growth retardation, 19 (95.0%) with fasting hypoglycemia, 14 (70.0%) with hyperlactatemia, 9 (45.0%) with hypertriglyceridemia, and 5 (25.0%) with hypercholesterolemia. Fasting blood ketone was measured for 8 patients and all of these patients had an increase in blood ketone; all patients had normal uric acid, and 5 patients (25.0%) had positive urine ketone. Liver biopsy was performed for 18 patients, among whom 15 had mild to moderate liver fibrosis. A total of 16 mutations were detected in the PHKA2 gene, among which 5 were known pathogenic mutations and 11 were novel mutations, and most of the mutations were detected in the c.3614 locus. All patients were treated with uncooked cornstarch, and most patients achieved an improvement in clinical manifestations. ConclusionGSD Ⅸa is more common in male patients. This disease should be considered for patients with hepatomegaly, elevated aminotransferases, growth retardation, fasting hypoglycemia, elevated fasting blood ketone, and normal uric acid. Liver biopsy may help with the diagnosis of this disease, and clinical biochemical parameters and gene detection can be used to confirm diagnosis and classification. Most patients have mild clinical manifestations, while some patients may have liver fibrosis, and treatment with uncooked cornstarch can improve the condition of this disease.

Anthropometric and dietary assessment of patients with glycogenosis type i / Avaliação antropométrica e dietética de pacientes com glicogenose tipo i

ABSTRACT Objective: To perform anthropometric and dietary evaluation of patients with glycogenosis type Ia and Ib. Methods: This cross-sectional study is composed of a sample of 11 patients with glycogenosis divided into two subgroups according to the classification of glycogenosis (type Ia=5 and type Ib=6), aged between 4 and 20 years. The analyzed anthropometric variables were weight, height, body mass index, and measures of lean and fat body mass, which were compared with reference values. For dietary assessment, a food frequency questionnaire was used to calculate energy and macronutrients intake as well as the amount of raw cornstarch consumed. Mann-Whitney U test and Fisher's exact test were performed, considering a significance level of 5%. Results: Patients ingested raw cornstarch in the amount of 0.49 to 1.34 g/kg/dose at a frequency of six times a day, which is lower than recommended (1.75-2.50 g/kg/dose, four times a day). The amount of energy intake was, on average, 50% higher than energy requirements; however, carbohydrate intake was below the adequacy percentage in 5/11 patients. Short stature was found in 4/10 patients; obesity, in 3/11; and muscle mass deficit, in 7/11. There were no statistical differences between the subgroups. Conclusions: In patients with glycogenosis type I, there was deficit in growth and muscle mass, but no differences were found between the subgroups (Ia and Ib). Although the diet did not exceed the adequacy of carbohydrates, about 1/3 of the patients presented obesity, probably due to higher energy intake.

RESUMO Objetivo: Realizar avaliação antropométrica e dietética de pacientes com glicogenose tipos Ia e Ib. Métodos: Estudo transversal composto de uma amostra de 11 pacientes com glicogenose divididos em dois subgrupos de acordo com a classificação da glicogenose (tipo Ia=5; tipo Ib=6), com idades entre 4 e 20 anos. As variáveis antropométricas analisadas foram peso, estatura, índice de massa corporal e medidas de massa magra e gorda, que foram comparadas com valores de referência. Para avaliação dietética, foi utilizado um questionário de frequência alimentar para cálculo de ingestão de energia e macronutrientes, além da quantidade de amido cru ingerida. Realizaram-se testes U de Mann-Whitney e exato de Fisher, com nível de significância de 5%. Resultados: Os pacientes ingeriram amido cru na quantidade de 0,49 a 1,34 g/kg/dose na frequência de seis vezes ao dia, inferior à dosagem preconizada (1,75-2,50 g/kg/dose quatro vezes ao dia). A quantidade de energia consumida foi, em média, 50% a mais que as necessidades, contudo o consumo de carboidratos foi abaixo da porcentagem de adequação em 5/11 pacientes. Baixa estatura ocorreu em 4/10 pacientes, obesidade em 3/11 e déficit de massa muscular em 7/11. Não houve diferença estatística entre os subgrupos. Conclusões: Em pacientes com glicogenose tipo I, houve déficit de crescimento e de massa muscular, mas não diferença significante entre os subgrupos (Ia e Ib). Embora a dieta não tenha ultrapassado a adequação de carboidratos, 1/3 dos pacientes apresentou obesidade, provavelmente pela maior ingestão de energia.