Late Recognition of Andersen's Disease in Advanced Heart Failure

Glucogen storage diseases such as Andersen's disease are inherited disorders of carbohydrate metabolism. Cardiac involvement in Andersen's disease is extremely unusual and difficult to diagnose, especially in elderly individuals with atypical presentations. The following is a case of a 61-year-old man with a family history of muscle weakness who presented with congestive heart failure and was found to have Andersen disease cardiomyopathy. The diagnosis was made in view of the normal negative workup for cardiomyopathy, massive glucose tetrasaccharide excretion, and normal alpha-glucosidase activity. The patient rapidly deteriorated and passed away. This case highlights the need to consider storage diseases in adults with nonischemic dilated cardiomyopathy of uncertain etiology in the presence of liver or muscle involvement

A Study of Chemical Composition of Gall Stones in a Tertiary Care Hospital.

Gallstones are a major health problem & have been recognized since antiquity. Gallstones are generally classified into pure cholesterol, pigment and mixed type. Knowing the chemical composition of gallstones is essential for determining etiopathogenesis of gallstone disease. Fourier Transform Infrared Spectroscopy (FTIR) method is the most widely used technique in chemical analysis of gall stones. Reports on chemical analysis of gallstones are available from different endemic regions of India. However, no reports are available about the composition and etiopathogenesis of gallstones in Himachal Pradesh. METHODSGallstones from 400 patients of cholelithiasis were collected after cholecystectomy at Indira Gandhi Medical College Hospital (I.G.M.C.), Shimla, between June 2016 to June 2018, and were subjected to chemical analysis by FTIR method. The data was further correlated with regard to age, gender, socio-economic status, various life style factors like diet, obesity, physical activity, with stone number and colour. RESULTSChemical analysis of gall stones revealed that pure cholesterol, mixed and pigment variety were 94 %, 2 % and 4 % respectively. Majority of the patients were below the age of 50 years (66 %). Male to female ratio was 2.7:1. Both sexes had predominantly pure cholesterol stones. Most of the patients belonged to the lower middle class (56.5 %) & all socio-economic classes showed predominantly pure cholesterol stones. Similarly, there was no predilection of any type of stone to a particular physical work category. 53.5 % patients were non-vegetarians and 46.5 % were vegetarians. There was no correlation between diet and BMI with type of stones. In our study, 66 % of patients had multiple stones. Multiple stones were seen in all varieties of stones. Pure cholesterol stones showed a variety of colours contrary to traditional classification. CONCLUSIONSIn Himalayan population, the predominant type of gall stones were pure cholesterol stones. Mixed stones and pigment containing stones were found in much smaller frequencies. This result is in contrast to that of rest of the Indian subcontinent from where larger percentage of pigment and mixed stones has been reported. And pure cholesterol stones showed maximum variation in colours contrary to our expectation.

Prevalence of Non-Alcoholic Fatty Liver with Gall Stones Disease in Himalayan Population

Non-Alcoholic Fatty Liver Disease (NAFLD) is the hepatic pandemic of the 21st century. It is the amassing of fats in the hepatic tissue without significant alcohol intake that results in hepatic steatosis. Patients with gall bladder stones may have associated NAFLD as these ailments share similar factors like obesity, hypertriglyceridemia and diabetes mellitus. However, few, if any, reports are available about the association of NAFLD with gallstones in the hilly population. Hence, this study was conducted to find out the prevalence of NAFLD in patients with gall bladder stone disease.METHODSThis study was done in the Department of Surgery, Indira Gandhi Medical College, Shimla, from June 2017 to May 2019. A total of 300 patients of ultrasound proven gall bladder stones was studied for NAFLD by Fibroscan (transient elastography). Transient elastography (TE) is a noninvasive method that has been shown to be useful for the detection of liver steatosis and fibrosis. NAFLD was diagnosed based on the value of CAP (Controlled Attenuation Parameter) & degree of fibrosis was assessed based on liver stiffness measurement (LSM) value on TE. Steatosis was graded as S0, S1, S2, and S3 while fibrosis was graded as F0-F1, F1, F2, F3, and cirrhosis. Minimum cut-off CAP value for diagnosing NAFLD was 214 dB/m & significant fibrosis was taken with LSM value >7.5 kPa.RESULTSPatients of gall stone disease showed significant liver steatosis, suggestive of NAFLD in 189 patients (63%), based on CAP value; however, 111 patients (37%) did not have significant steatosis. In patients with NAFLD, 57 (30%) had mild steatosis (s1) while 39 (20.53%) & 24 (12.63%) had moderate (s2) and severe (s3) steatosis respectively. Similarity, 72 (24%) patients had significant fibrosis while 228 (76%) patients had no to insignificant fibrosis on TE, 51 (17%) patients had moderate fibrosis, while 14 (4.5%) and 8 (2.5%) patients had severe fibrosis & cirrhosis respectively.CONCLUSIONSHigh prevalence of NAFLD in patients of gall stone disease was observed. Most of the patients had mild NAFLD i.e. grade S1 steatosis & in addition, fibrosis was present in 24% patients of NAFLD with gall stone disease.

Clinical characteristics and genetic analysis of adult late-onset glycogen storage disease type II / 上海交通大学学报（医学版）

Objective: To investigate the clinical and genetic characteristics of adult late-onset glycogen storage disease type Ⅱ (GSD Ⅱ ). Methods: The clinical data, muscular magnetic resonance imaging (MRI) and muscle pathological characteristics of a patient with late-onset GSD Ⅱ were retrospectively analyzed and his family history was investigated. Peripheral blood DNAs of the proband and his father were extracted for genetic testing. Results: The proband presented progressive limb weakness for 7 years and short of breath after activities for 2 years. His parents were inbred, but he was the only one among the 18 members of 5 generations who had clinical phenotype. The blood creatine kinase moderately increased. The muscle MRI of both lower limbs showed that muscles were severely atrophied, and the fat component increased significantly. The pathological findings of muscle biopsy indicated vacuolar degeneration and increased activity of acid phosphatase. Gene sequencing confirmed that the pathogenicity was a homozygous mutation of acid α-glucosidase (GAA) gene c.1634C>T, and his father was a heterozygous mutation of c.1634C>T. Conclusion: Homozygous mutations of GAA gene c.1634C>T may lead to late-onset GSD Ⅱ.

Glucogenosis Hepática. Características clínicas, laboratoriales e imagenológicas en pacientes pediátricos menores de 15 años / Hepatic glycogenosis. Clinical, laboratory and imaging characteristics in pediatric patients under 15 years old

Antecedentes: La glucogenosis (GSD) hepática es una enfermedad hereditaria autosómica recesiva caracterizada por la alteración del depósito de glucógeno en los tejidos. La enfermedad se presenta con hepatomegalia, debilidad muscular y retraso del crecimiento. Esta patología usualmente se diagnostica clínicamente a partir de los 6 meses de edad cuando la ingesta de alimentos del lactante es más espaciada y puede debutar con sintomatología de hipoglicemia. Debido a la inespecificidad de la presentación clínica de la enfermedad es muy importante la sospecha diagnóstica desde los centros de primer nivel de atención y su derivación oportuna a centros de especialidad. Objetivo: Evaluar y describir el perfil nutricional y clínico en pacientes menores de 15 años con Glucogenosis Hepática. Método: Se describe una serie de casos de 14 pacientes menores de 15 años con diagnóstico clínico de GSD hepática, atendidos en la consulta de Gastroenterología y Nutrición Pediátrica del Hospital Carlos Andrade Marín entre 2016 y 2018. El diagnóstico se lo realizó de acuerdo a la clínica que presentó cada paciente como la presencia de distensión abdominal, hepatomegalia, adinamia, retraso en el crecimiento y datos laboratoriales como niveles de glicemia en sangre periférica, transaminasas, y realización de elastografía entre los principales. Se analizaron datos sociodemográficos, antropométricos, de laboratorio (transaminasas, glicemia periférica) y elastografía hepática. Para el análisis de datos se creó una base de datos en Microsoft Excel 2013 y se procesó con el programa Epi Info 7. Resultados: En este grupo de casos, los tipos específicos de GSD hepática fueron tipo IX, 57,14% (8), tipo III, 28,57% (4) y tipo Ia-b, 14,29% (2) pacientes. La prevalencia de características clínicas ante la sospecha de la GSD hepática fueron: hepatomegalia 100% (14), y retraso en el crecimiento el 64,3% (9). De acuerdo a los exámenes de sangre periférica los valores promedio de transaminasas hepáticas (AST/TGO U/L) (ALT/TGP U/L) y glucosa, fueron de 364±384, 302±255 y 61±15 mg/dL, respectivamente. La elastografía con la que se evaluó el nivel de fibrosis hepática al momento del diagnóstico arrojó los siguientes resultados: F0 (no fibrosis hepática) en el 28,57% (4), F1 con el 28,57% (4), F2-F3 con el 35,71% (5), y F4 7,14%. Conclusión: La Glucogenosis es una patología que debería ser sospechada a tiempo en centros del primer nivel de salud para luego referir oportunamente los casos a los centros de referencia. La hepatomegalia y el retardo en el crecimiento son signos cardinales de alerta para la sospecha de esta patología.

Novel SLC37A4 Mutations in Korean Patients With Glycogen Storage Disease Ib

BACKGROUND: Molecular techniques are fundamental for establishing an accurate diagnosis and therapeutic approach of glycogen storage diseases (GSDs). We aimed to evaluate SLC37A4 mutation spectrum in Korean GSD Ib patients. METHODS: Nine Korean patients from eight unrelated families with GSD Ib were included. SLC37A4 mutations were detected in all patients with direct sequencing using a PCR method and/or whole-exome sequencing. A comprehensive review of previously reported SLC37A4 mutations was also conducted. RESULTS: Nine different pathogenic SLC37A4 mutations were identified in the nine patients with GSD Ib. Among them, four novel mutations were identified: c.148G>A (pGly50Arg), c.320G>A (p.Trp107*), c.412T>C (p.Trp138Arg), and c.818G>A (p.Gly273Asp). The most common mutation type was missense mutations (66.7%, 6/9), followed by nonsense mutations (22.2%, 2/9) and small deletion mutations (11.1%, 1/9). The most common mutation identified in the Korean population was c.443C>T (p.Ala148Val), which comprised 39.9% (7/18) of all tested alleles. This mutation has not been reported in GSD Ib patients in other ethnic populations. CONCLUSIONS: This study expands knowledge of the SLC37A4 mutation spectrum in Korean patients with GSD Ib.

Clinical and gene mutation analysis of three children with late-onset glycogen storage disease type Ⅱ with hypertrophic cardiomyopathy / 中华儿科杂志

Objective@#To investigate the clinical and laboratory features of three children with late-onset type Ⅱ glycogen storage disease(GSD) who presented with hypertrophic cardiomyopathy and to analyze the effect of five mutations identified on the acid-α-glucosidase (GAA) activity and stability.@*Method@#Three cases of children with muscle weakness were included in this study.GAA activity was analyzed in Dried Blood Spot of the patients.DNA was extracted from peripheral blood in all the patients and their parents and subjected to polymerase chain reaction and directly sequencing of GAA gene.Five mutant pcDNA3.1-myc-his-GAA expression plasmids(p.G478R, p.P361L, p.P266S, p.Q323X, p.R672Q) were constructed and transient instantaneously transfected into 293T cells to analyze the enzyme activity and stability of GAA.@*Result@#All the three children had the onset of disease at 3 years or 1.5 years of age.They presented with developmental delay, muscle weakness and hypertrophic cardiomyopathy.GAA activity of 3 patients was 2.65, 3.55 and 1.51 pmol(punch·h)(8.00-98.02)respectively. Genetic analysis found 5 mutations (p.G478R, p. P361L, p. P266S, p. Q323X, p. R672Q), and all of these 3 cases had clinical manifestations and were diagnosed as late-onset type Ⅱ glycogen storage disease.Five mutant pcDNA3.1-myc-his-GAA expression plasmids were transfected into 293T cells.Five mutant enzyme activities were found to be only 9.9%-22.5% of the wild-type enzyme activity and the protein expression of the five mutants was 32.0%-63.9% compared with the wild type.@*Conclusion@#This study reports 3 children with late-onset GSD Ⅱ accompanied by hypertrophic cardiomyopathy and compensatory stage of cardiac function in addition to limb muscle weakness.Five pathogenic mutations were identified, and these 5 mutations result in decreased GAA activity and GAA expression by in vitro functional analysis.

The Effect of Gallstone Presentation on Treatment Outcome in Symptomatic Cholelithiasis

Introduction: Gall stone disease (GSD) is a common surgical problem. Surgical treatment of  asymptomatic GSD is still controversial. Complicated GSD has varied presentation and contributes substantially to healthcare costs and may be life threatening. The present study is aimed to know the effect of gall stone presentation on treatment outcome. Methodology: This is a retrospective study conducted in a tertiary health care centre. All patients who underwent cholecystectomy (open or laparoscopic) were included in the study and were grouped in uncomplicated (Group A) and complicated group (Group B), depending upon their presentation. Treatment outcome was analysed for various measures i.e. type of admission (emergency or elective), length of hospital stay, postoperative complications, type of surgery and mortality. Observations: Out of the 202 patients, 109 (53.9%) were in group A and 93 (46.1%) were in group B. Acute cholecystitis comprised 30.1% of complicated GSD, whereas gall stone pancreatitis, choledocholithiasis, mucocele, empyema gall bladder, perforation and gall stone ileus comprised 6.9%, 2.9%, 3.9%, 0.9%, 0.4% and 0.4% respectively. Comparatively, patients with uncomplicated GSD were admitted electively, were mostly managed laparoscopically and had lower incidence of post-operative complications and hence shorter length of hospital stay and lower treatment cost. Conclusion: Most of the patients who present early in course of GSD have better treatment outcome. We recommend early elective laparoscopic surgery for all patients who present with initial symptoms of GSD.

Structured Dietary Management Dramatically Improves Marked Transaminitis, Metabolic and Clinical Profiles in Glycogen Storage Disease Type IXa

Abstract Glycogen storage disease type IXa (GSD IXa) presents in childhood with hepatomegaly, poor growth, and ketotic hypoglycemia. Clinical course is usually mild, often not requiring treatment with attenuation of symptoms with increasing age. The phenotypic spectrum has recently expanded to include more severe involvement with hepatic fibrosis or cirrhosis warranting dietary therapy. We report a 2-year-old boy with a severe phenotype of GSD IXa presenting with a massive hepatomegaly, significant transaminitis, recurrent ketotic hypoglycemia, and short stature. Aggressive dietary management with regular feeds, frequent uncooked cornstarch doses, and protein supplementation resulted in clinical improvements including enhanced growth velocity, energy levels, overall well-being, and reduction in hepatomegaly with restitutions in biochemical parameters. We concur with a recent report which proposed that GSD IXa is not always a mild condition but instead part of an expanding phenotypic spectrum warranting intensive dietary management to optimize metabolic control and quality of life.

Enfermedad de vnn gierke: nuevas tendencias en el manejo / Von gieke diseasse: new trends in management / Doença de vn gieerke: novas tendências no tratamento

La enfermedad de von Gierke, también conocida como enfermedad de deposito de glucógeno tipo Ia, es una enfermedad producida por la deficiencia de la unidad catalítica de la G6Pasa-a, encargada de hidrolizar la glucosa 6 fosfato en el citoplasma celular durante la gluconeogénesis y la glucogenolisis. Las complicaciones a largo plazo son hipoglicemia severa y alteraciones en el crecimiento. En los niños más pequeños la enfermedad típicamente se presenta con crisis convulsivas y hepatomegalia que se manifiestan a los 6 y 8 meses. Otras complicaciones son osteoporosis, gota, enfermedad renal, hipertensión pulmonar y adenomas hepáticos que pueden malignizarse. No se ha encontrado una cura y de no recibir un manejo adecuado es letal en las primeras dos décadas de la vida. El tratamiento consiste en terapia nutricional, asociada a varios medicamentos convencionales. Algunos pacientes pueden requerir transplante renal o transplante hepático. Una nueva esperanza se ha abierto con el advenimiento de la terapia génica con vectores virales, esta estrategia hasta ahora esta siendo desarrollada, pero los estudios realizados han mostrado una luz de esperanza para investigadores, médicos y pacientes. Faltan estudios para que estos tratamientos permitan un beneficio a largo plazo y su aplicación en humanos, ya que las pruebas como es de esperarse solo han sido desarrolladas en modelos animales.

Von Gierke disease, also known as glycogen storage disease type Ia, is a disease caused by deficiency of the G6Pase-a catalytic unit, which hydrolyzes glucose-6- phosphate in the cell cytoplasm during gluconeogenesis and glycogenolysis. Long term complications include severe hypoglycemia and growth disturbances. In small children, the disease typically presents with seizure crisis and hepatomegaly which become manifest at the age of 6 and 8 months. Other complications include osteoporosis, gout, renal disease, pulmonary hypertension and hepatic adenomas which can become malignant. No cure has been found for this disease and it can turn out to be lethal if no appropriate management is given during the first two decades of life. The treatment consists of nutritional therapy associated with a number of conventional drugs. Some patients may require renal or liver transplant. A new hope has emerged with the arrival of gene therapy with viral vectors, strategy that is being developed hitherto, yet performed studies have shown a glimmer of hope for investigators, doctors and patients. There is a need for studies so these treatments allow for a longer term benefit and their application in humans since, as expected, the tests have been developed only in animal models.

A doença de Von Gierke, também conhecida como Glicogenose tipo I, é uma doença produzida pela deficiência da unidade catalítica da G6Pasa-a, encarregada de hidrolisar a glicose 6 fosfato no citoplasma celular durante a gliconeogênese e a glicogenólise. As complicações a longo prazo são hipoglicemia severa e alterações no crescimento. Nas crianças menores a doença se apresenta tipicamente com crises convulsivas e hepatomegalia que se manifestam aos 6 e 8 meses. Outras complicações são osteoporose, gota, doença renal, hipertensão pulmonar e adenomas hepáticos que podem malignizar-se. Não foi encontrada uma cura e se não recebe tratamento adequado é letal nas primeiras duas décadas de vida. O tratamento consiste em terapia nutricional, associada a vários medicamentos convencionais. Alguns pacientes podem requerer transplante renal ou transplante hepático. Uma nova esperança apareceu com a terapia gênica com vetores virais, esta estratégia até agora esta sendo desenvolvida, mas os estudos realizados mostram uma luz de esperança para pesquisadores, médicos e pacientes. Faltam estudos para que estes tratamentos permitam um beneficio a longo prazo e a sua aplicação em humanos, já que os testes como é de se esperar só foram desenvolvidos em modelos animais.

General Anesthesia in a Patient with Infantile Pompe's Disease : A case report

Pompe's disease (type II glycogen storage disease) is an autosomalrecessive disorder caused by a deficiency of lysosomal acid alpha- glucosidase (GAA) leading to the accumulation of glycogen in the lysosomes primarily in cardiac and skeletal muscle. Recently a promising enzyme replacement therapy has resulted in improved clinical outcomes and a resurgence of elective anesthesia for these patients. The anesthetic management of infant with Pompe's disease presents a variety of challenges. Therefore, understanding the unique cardiac and respiratory physiology is essential to providing safe general anesthesia. We report a case of patient with infantile-onset Pompe's disease who underwent a tracheostomy for a ventilator care.

A Novel Mutation (A148V) in the Glucose 6-phosphate Translocase (SLC37A4) Gene in a Korean Patient with Glycogen Storage Disease Type 1b

We report a Korean patient with glycogen storage disease type 1b (GSD-1b) whose diagnosis was confirmed by liver biopsy and laboratory results. The patient presented with delay of puberty and short stature on admission and had typical clinical symptoms of GSD as well as chronic neutropenia and inflammatory bowel disease. Mutation analysis of the glucose 6-phosphate translocase 6-phosphate translocase (SLC37A4) gene revealed that the patient was a compound heterozygote of two different mutations including a deletion mutation (c.1042_1043delCT; L348fs) and a missense mutation (A148V). The L348fs mutation was inherited from the patient's father and has been reported in an Italian family with GSD-1b, while the A148V mutation was transmitted from the patient's mother and was a novel mutation. To the best of our knowledge, this is the first report of genetically confirmed case of GSD-1b in Korean.

Mutation Analysis of Korean Patients with Glycogen Storage Disease Type Ia / 대한소아소화기영양학회지

PURPOSE: Glycogen storage disease type Ia (GSD Ia) is an autosomal recessive disorder of glycogen metabolism caused by glucose-6-phosphatase (G6Pase) deficiency. The clinical manifestations of G6Pase deficiency include growth retardation, hepatomegaly, hypoglycemia, lactic acidemia, hyperlipidemia and hyperuricemia. Many mutations of this gene have been found worldwide in various ethnic groups, establishing the molecular basis of GSD Ia. To elucidate a spectrum of the G6Pase gene mutations in Korean, we analyzed mutations in Korean patients with GSD Ia. METHODS: Both alleles of 9 unrelated GSD 1a patients were studied by PCR and direct DNA sequencing methods. In all patients, GSD 1a was diagnosed by the enzyme assay for the liver biopsy specimen. RESULTS: In Korean, the most prevalent mutation was g727t substitution in exon 5, which has been reported to cause abnormal mRNA splicing: Sixteen out of 18 alleles were found to have this mutation. In addition, we identified one novel mutation, a c611g, converting a proline to an alanine at codon 178. CONCLUSION: Our findings suggest that a screening for the g727t mutation by noninvasive molecular method can detect most cases of GSD Ia in Korean patients.

A Case of Glycogen Storage Disease Type lb

Glycogen storage disease(GSD) type lis due to defect of glycose-6-phosphatase at the membrane of the endoplasmic reticulum in liver. Clinical presentations of GSD 1 are massive hepatomegaly without splenomegaly, failure to thrive, bleeding tendency, hypoglycemia, fasting ketosis and hyperlipidemia. The appearance of patient is short and fat with particularly fat cheeks. Mental development is usually normal. It was diagnosed by liver biopsy and cofirmend as GSD type lby enzyme analysis. We have experienced a case of GSD type land reported with brief review of literatures