Niemann-Pick disease type B and heterogeneous manifestations of its liver involvement： A case report / 临床肝胆病杂志

This article reports a case with the chief complaint of “hepatosplenomegaly to be investigated” and a confirmed diagnosis of Niemann-Pick disease type B after various tests， and a literature review was conducted to summarize the heterogeneous manifestations of liver involvement in type B Niemann-Pick disease， in order to improve the clinical management of difficult and rare liver diseases.

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.

Consenso Argentino sobre Diagnóstico y Tratamiento de la Enfermedad de Niemann-Pick tipo C / Argentinean Consensus on the Diagnosis and Treatment of Niemann-Pick Disease type C

Resumen La enfermedad de Niemann-Pick tipo C (NPC) es un trastorno del metabolismo lisosomal que se debe a la presencia de variantes patogénicas bialélicas en los genes NPC1 o NPC2. El depósito intracelular de lípidos, especialmente colesterol no esterificado, provoca daño oxidativo en diversos tejidos, especialmente neuronas, bazo e hígado. Esto, a su vez, induce la aparición de un conjunto de síntomas neurológicos/psiquiátricos y viscerales, con una amplia variabilidad de edad de apa rición, desde formas prenatales/neonatales hasta otras de aparición en la vida adulta. En los últimos años ha habido avances considerables en la comprensión sobre esta enfermedad y su manejo. En el presente consenso un grupo de expertos argentinos abordan los enfoques actuales de diagnóstico, seguimiento y tratamiento de NPC, incluyendo el uso de miglustat como única terapia específica aprobada en la actualidad.

Abstract Niemann-Pick type C (NPC) is a disorder of the lyso somal metabolism due to biallelic pathogenic variants in NPC1 or NPC2. Intracellular deposit of lipids, mainly unesterified cholesterol, gives rise to oxidative damage in several tissues, mainly neurons, spleen and liver. This, in turn, is associated with a myriad of neurologi cal/psychiatric and visceral symptoms, with wide vari ability in age of presentation, from prenatal/neonatal to adult-onset forms of the disease. The last few years have seen considerable progress in understanding this disease and its management. In this consensus, current approaches to the diagnosis, follow-up and treatment of NPC (including the use of miglustat, the only specific drug approved at the time) are discussed by an Argentin ian panel of experts.

Rehabilitación en la enfermedad de Pompe / Pompe disease rehabilitation management

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.

Tratamiento de la enfermedad de Pompe / Treatment of Pompe Disease

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.

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.

A family of Niemann-Pick disease type C caused by compound heterozygous mutations in NPC1 gene / 中华神经科杂志

Objective:To report the clinical and genetic characteristics of a family with Niemann-Pick disease type C caused by novel compound heterozygous mutations in the NPC1 gene to improve the clinicians′ recognition of the disease. Methods:Two patients from the family with non-consanguineous marriages admitted to the Department of Neurology of the First Affiliated Hospital of Kunming Medical University in 2020 were examined in detail. Peripheral blood DNA was extracted, and whole exome sequencing was performed on the patients, combined with Sanger sequencing for verification. The mutation and protein function predictor softwares were applied to analyze the mutation sites.Results:The inheritance was autosomal recessive in this family. The onset age of the proband was 9 years, and the main clinical manifestations were dysarthria, dysphagia, cognitive impairment, ataxia, bilateral pyramidal tract impairment, vertical supranuclear gaze palsy and splenomegaly. The clinical phenotype of the proband′s younger brother was similar to that of the proband, but it was more severe than that of the proband. The younger brother of the proband had an earlier age of onset and severe psychomotor retardation. Whole exome sequencing showed that both brothers carried 2 rare variants of NPC1 gene:1 pathogenic, stop gain at c.352_353del, p.Gln119ValfsTer8, and a missense change, c.593A>G, p.Asn198Ser, of suspected pathogenic. Sanger sequencing confirmed that compound heterozygous mutations were derived from the proband′s parents. According to the American College of Medical Genetics and Genomics guidelines, the above variants were rated as pathogenic and suspected pathogenic, respectively. And the c.593A>G, p.Asn198Ser mutation found in this family was a novel one which had not been reported yet. The proband had delayed diagnosis for 7 years from the onset of symptoms. After taking megastat for 1 year, the symptoms of dysphagia, ataxia and vertical eye movement disorder were significantly improved. Conclusions:The clinical phenotype of the pedigree was consistent with the clinical phenotype of Niemann-Pick disease type C. Compound heterozygous mutations of NPC1 gene (c.352_353del; c.593A>G) were found to be the genetic cause of the family.

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.

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.

Molecular and functional study of pediatric patients with Niemann-Pick C in Argentina / Estudio molecular y funcional de pacientes pediátricos con Niemann-Pick C en Argentina

Abstract Niemann-Pick type C (NP-C) is a rare, autosomal recessive disorder. At least 95% of all the cases with this disease are due to mutations in the NPC1 gene. The clinical signs and symptoms of NP-C are classified into visceral, neurological and psychiatric. Our aim is to report the clinical findings, molecular results and filipin staining of 4 patients. The age of onset, expressed as median and range, was 0.2 (0.08-4.0) years and the age of diagnosis was 4.0 (2.5-8.9) years. Neurological and/or visceral manifestations were presented in our patients. Foamy cells in bone marrow biopsy were found in two patients. Through a molecular analysis of NPC1 gene, one non-reported (novel) and 4 previously described mutations were found. The filipin staining showed a positive pattern in all the patients. The diagnostic confirmation of these pediatric patients means a contribution to the casuistry of this disease in Argentina.

Resumen Niemann-Pick tipo C (NP-C) es una enfermedad poco frecuente, con un patrón de herencia au tosómico recesivo. Al menos el 95% de los casos se producen por mutaciones en el gen NPC1. Los signos y síntomas clínicos de NP-C se clasifican en viscerales, neurológicos y psiquiátricos. En este trabajo presentamos los hallazgos clínicos, los resultados moleculares y la tinción con filipina de 4 pacientes con NP-C. La edad de presentación de los primeros síntomas, expresada como mediana y rango, fue de 0.2 años (0.08-4.0) años y la edad del diagnóstico fue 4.0 (2.5-8.9) años. Los pacientes presentaron manifestaciones neurológicas y / o vis cerales. Se encontraron células espumosas en la biopsia de médula ósea en 2 pacientes. El análisis molecular del gen NPC1 encontró 1 variante nueva y 4 previamente publicadas. La tinción de filipina mostró un patrón positivo en todos los pacientes. La confirmación diagnóstica de este grupo de pacientes pediátricos significa un aporte a la casuística de esta enfermedad en Argentina.

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

Analysis on the status quo of 0-14 years old children′s cross-provincial medical treatment in Shandong province / 中华医院管理杂志

Objective:To analyze the current situation and problems of cross-provincial medical treatment for children in Shandong province, and put forward corresponding countermeasures.Methods:The FUTang Updating medical REcords(FUTURE)database established by Futang Children′s Medical Development Research Center was selected to extract the data of 0-14 years old children who were discharged outside Shandong province from January 1, 2019 to December 31, 2020 and whose current address was in Shandong province, and the data of hospitalized children in a children′s hospital in Shandong province during the same period were selected for comparison. The SPSS 22.0 software was used to establish the database, and statistics and analysis were made on the number of cases, main flow direction, departments, types of diseases and hospitalization cost of children.Results:A total of 13 071 cases accepted cross-provincial medical treatment were included, and the main flow of medical treatment was Beijing Children′s Hospital. The data of 87 742 children admitted to a children′s hospital in Shandong province at the same time were included. The proportion of female and school-age children in children accepted cross-provincial medical treatment was higher than that of local patients, and the hospitalization cost was higher than that of local patients. The main diseases for children seeking medical treatment outside the province were tumors, immune diseases and other serious diseases or chronic diseases, while the main diseases for children seeking medical treatment in the province were respiratory diseases such as pneumonia.Conclusions:The proportion of tumors and immune diseases among children aged 0-14 years accepted cross-provincial medical treatment is relatively high. Hospitals in Shandong province should pay attention to the construction of key specialties, actively develop new technologies and new businesses, and enhance the core competitiveness of hospitals. At the same time, we should improve the medical service system and guide patients to seek medical care reasonably through policies.

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 features of a pedigree of charcot-marie-tooth disease type 2cc caused by the point mutation of NEFH gene / 中华实用儿科临床杂志

The clinical data of 4 patients in a pedigree of charcot-marie-tooth disease type 2cc (CMT2cc) caused by the NEFH gene mutation from the Department of Rehabilitation, Tianjin Children′s Hospital in March 2020 were reviewed and analyzed retrospectively.The purpose of this study was to improve clinicians′ awareness of the di-sease.The pedigree had signs and symptoms of varying degrees of pyramidal fasciculus involvement, high arched feet, and achilles tendon contracture.The electrophysiological testing of both lower extremities suggested sensory and motor nerve axonal damage, and an abnormal visual evoked potential was observed.Second-generation sequencing revealed that the pathogenic factor was the NEFH gene variation: c.1319G>A (p.Ser440Asn), which is a new mutation site that has never been reported before. NEFH mutations can cause a complex clinical phenotype of CMT2cc, which is therefore easily misdiagnosed.Central and peripheral nerves are simultaneously involved in CMT2cc patients.Electrophysiological testing and genetic analysis are required to clarify the diagnosis of CMT2cc.

Clinical features of a pedigree of charcot-marie-tooth disease type 2cc caused by the point mutation of NEFH gene / 中华实用儿科临床杂志

The clinical data of 4 patients in a pedigree of charcot-marie-tooth disease type 2cc (CMT2cc) caused by the NEFH gene mutation from the Department of Rehabilitation, Tianjin Children′s Hospital in March 2020 were reviewed and analyzed retrospectively.The purpose of this study was to improve clinicians′ awareness of the di-sease.The pedigree had signs and symptoms of varying degrees of pyramidal fasciculus involvement, high arched feet, and achilles tendon contracture.The electrophysiological testing of both lower extremities suggested sensory and motor nerve axonal damage, and an abnormal visual evoked potential was observed.Second-generation sequencing revealed that the pathogenic factor was the NEFH gene variation: c.1319G>A (p.Ser440Asn), which is a new mutation site that has never been reported before. NEFH mutations can cause a complex clinical phenotype of CMT2cc, which is therefore easily misdiagnosed.Central and peripheral nerves are simultaneously involved in CMT2cc patients.Electrophysiological testing and genetic analysis are required to clarify the diagnosis of CMT2cc.

Advance in Niemann-Pick disease type C / 国际儿科学杂志

Niemann-Pick disease type C is a lipid storage disorder associated with impaired intracellular cholesterol trafficking, caused by mutations of either NPC1 or NPC2 genes.According to the age at onset of symptoms, it is divided into 5 categories, including neonatal, early-infantile, late-infantile, juvenile and adult type.There are differences in clinical manifestations and prognoses among each category.The characteristic clinical manifestations are hepatosplenomegaly, lung infiltration, vertical supranuclear gaze palsy and gelastic cataplexy.The definite diagnosis requires demonstration of unesterified cholesterol accumulated in fibroblasts cultured from skin biopsies with filipin staining and(or) of pathogenic mutation of NPC1/NPC2 genes.There is no effective treatment for this disease yet, therefore the overall prognosis is still poor.Miglustat can delay onset of the neurological symptoms, and prolong survival of partial patients.

The influence of hematopoietic stem cell transplant on pulmonary involvement in pediatric type B Niemann-Pick disease: high resolution CT findings / 中华放射学杂志

Objective:To analyze the pulmonary high resolution CT (HRCT) images before and after hematopoietic stem cell transplantation (HSCT) in 6 children with Niemann-Pick disease(NPD) type B, and to investigate the effect of HSCT on lung lesions.Methods:Data of 6 children who were diagnosed with NPD type B and underwent HSCT treatment in Children′s Hospital Affiliated to Capital Institute of Pediatric from March 2019 to June 2021 were retrospectively enrolled, including 5 males and 1 female, with ages ranging from 1 year and 2 months to 5 years, and a median age of 2 years and 1month. The follow-up time of HRCT after HSCT was 7-20.5 months, the median time was 5 months, and the number of follow-up was 2-7 per patients, a total of 27 times. The pulmonary lesions (including interstitial lung disease, airway lesions and alveolar lesions) on aortic arch level, tracheal carina level and right diaphragmatic surface level were evaluated and scored respectively by two experienced pediatric radiologists, and the average score between them would be the final score. The Kruskal-Wallis H test was used to compare the scores of the three kinds of lung lesions before HSCT. The linear regression method was used to analyze the impact of HSCT duration on the degree of different lesions. To control possible confounding factors in the study, a generalized linear mixed model was used to evaluate the effects of HSCT duration, age, gender and whether co-infection on different types of lesions after HSCT. Results:Before HSCT treatment, all of the 6 children had different degree of airway, interstitial and alveolar lesions, with a median score of 3.0, 14.0 and 5.8 points, respectively (χ2=11.95, P=0.003). Interstitial disease was the most extensive and serious lesion among those three pulmonary involvements in pediatric NPD type B. After HSCT treatment, the scores of interstitial and airway lesions in all of the 6 children reduced, in varying degree, with the increase of time after HSCT. Except case 4, the alveolar lesion in 5 patients also showed a decreasing trend over time. The linear regression equation between the score of airway, interstitial, alveolar lesions and the HSCT duration was: airway lesion, Y=1.94-0.15X; interstitial lesion, Y=12.73-0.78X; and alveolar lesion, Y=3.31-0.27X. The results of the generalized linear mixed model showed that the main effect of HSCT duration significantly affected on the three kinds of lung lesions, and the scores of interstitial lesions, airway lesions and alveolar lesions were decreased by 0.688, 0.245, and 0.338 points for each 1 month increase of HSCT duration (all P<0.05). The alveolar lesion score decreased by 1.135 points for each 1 year increase in age at presentation ( P=0.012). The main effects of gender and co-infection were not statistically significant in all of the pulmonary lesions (both P>0.05). Conclusion:HSCT alleviates pulmonary lesions of children with NPD type B significantly and consistently, with interstitial lesions were the most prominent.

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.

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.