Case Of Glycogen Storage Disease Research Articles

Glycogen storage disease type Ia misdiagnosed as multiple acyl-coenzyme A dehydrogenase deficiency by mass spectrometry.

To report a case of glycogen storage disease (GSD) type Ia misdiagnosed as multiple acyl-coenzyme a dehydrogenase deficiency (MADD) by mass spectrometry. A 7 months old boy was admitted to our hospital for elevated transaminase levels lasting more than 1 month. His blood biochemistry showed hypoglycemia, metabolic acidosis, hyperlipidemia, elevated lactate and uric acid, elevated alanine amino transferase (ALT), aspartate amino transaminase (AST) and gamma-glutamyl transferase (GGT). Mass spectrometry analysis of blood and urine showed elevated blood acylcarnitines and dicarboxylic aciduria, indicating multiple acyl-coenzyme A dehydrogenase deficiency. Sanger sequencing of all exons of glucose-6-phosphatase (G6Pase) and electronic transfer flavoprotein dehydrogenase (ETFDH) was performed for the patient and his parents. Coding and flanking sequences of the G6Pase gene detected two heterozygous single base substitutions in the boy. One variant was in exon 1 (c.209G > A), Which was also detected in the father. Another was in exon 5 (c.648G > T), which was detected in the mother. Coding and flanking sequences of the ETFDH gene revealed no pathogenic/likely pathogenic variants in the boy. GSD Ia can manifest elevated blood acyl carnitines and dicarboxylic aciduria which were the typical clinical manifestations of MADD. So the patient with clinical manifestations similar to MADD is in need of differential diagnosis for GSD Ia. Genetic testing is helpful to confirming the diagnosis of inherited metabolic diseases.

Use of electron microscopy when screening liver biopsies from neonates and infants: experience from a single tertiary children’s hospital (1991-2017)

ABSTRACT Background: Although the role of electron microscopy is diminishing in several areas of adult pathology, it remains an essential tool for the study of pediatric liver biopsies. Methods: Clinical charts, histologic slides and EM materials of native liver biopsies from patients <1 year old (1991–2017) were reviewed. Results: 677 biopsies were performed on 353 males and 324 females. This study presents the concrete numbers for both the indications and the diseases, and describes the role of EM. EM was performed on 24.7% of liver biopsies and demonstrated key pathologic findings in 10 cases (6%), which led to the appropriate biochemical and/or genetic testing to confirm the diagnoses. The cases included five cases of glycogen storage disease with characteristic findings with cytoplasmic glycogen accumulation, two cases of mitochondrial disorder with pleomorphic mitochondria with crystalloid inclusions and one case each of Niemann-Pick Disease with abundant myelinosomes, Alpha-1 antitrypsin deficiency with deposits in the endoplasmic reticulum and infantile Refsum disease with trilamellar inclusions and lack of peroxisomes. In this study, we describe the detailed histologic and EM findings of each case . Conclusion: EM played an important screening and diagnostic role in the challenging cases and was also used to rule out detectable pathologic conditions.

Forbes Disease: A Case Report

Glycogen storage disease (GSD) type 3 (Forbes disease) is an autosomal recessive inborn error of metabolism caused by loss of function mutations of the glycogen debranching enzyme (Amylo- 1, 6-glucosidase [AGL]) and (oligo-1,4-1,4-glucanotransferase) gene, which is located at chromosome band 1p21.2. GSD 3 is characterized by the storage of structurally abnormal glycogen, termed limit dextrin, in both skeletal and cardiac muscle and/or liver, with great variability in resultant organ dysfunction. Here we describe a 16 yearold boy diagnosed as a case of epilepsy at the ageof 8. He presented to us with inadequately controlled seizure, profound proximal weakness, hepatosplenomegaly and right-sided ballotable kidney. The final diagnosis of glycogen storage disease was made by clinical features, lab reports and liver histopathology that revealed PAS positive diastase labile glycogen accumulation within swollen hepatocytes. The particular interest of this paper is to present a case of glycogen storage disease and demonstrate the difference between that entity and other storage diseases.Birdem Med J 2017; 7(1): 60-63

Clinical significance of histopathologic and ultrastructural pathologic examination in etiological diagnosis of infantile cholestatic diseases

To study the features of histopathologic and ultrastructural pathologic changes of liver biopsy in patients with infantile cholestatic disease, and to investigate its diagnostic significance combining with the clinical data. Thirty-six children diagnosed as infantile cholestatic disease and received liver biopsy in Chongqing Medical University Children's Hospital from Jun 2007 to Oct 2008 were enrolled and the pathologic and ultrastructural pathologic changes of liver were analyzed. Morphologic changes under light microscope in liver tissues included hepatocyte swelling, hepatocyte denaturation, hepatocyte necrosis, multinucleated giant cell formation, bile duct proliferation, fiber tissues proliferation and inflammatory cells infiltration in liver lobules and portal regions. The characteristics of cholestasis including intralobular cholestasis, acinus formation, feather-like cytoplasmic filaments and bile stasis in bile canaliculi were observed. The morphologic changes of biliary atresia were observed in 7 cases whose image investigations showed no obstruction of biliary tract. Nuclear changes, resolution of cytoplasm, inflammatory cell infiltration, collagen fiber proliferation and increased number of lysosomes were observed under electromicroscope. Two cases of glycogen storage disease, 1 case of Niemann-Pick disease and 1 case of lipid storage disease with unknown cause were confirmed by the combination of histological changes and clinical manifestations. Common pathologic changes of liver tissues existed under light microscope or electroscope. The diagnosis of hereditary metabolic disorders could be made increasingly by application of these two technologies in clinical practice. It is difficult to diagnose biliary atresia in early childhood by image investigations and the pathological changes of liver tissues are helpful.

A case of simultaneously identified glycogen storage disease and mucopolysaccharidosis

Glycogen storage disease (GSD) and mucopolysaccharidosis (MPS) are both independently inherited disorders. GSD is a member of a group of genetic disorders involving enzymes responsible for the synthesis and degradation of glycogen. GSD leads to abnormal tissue concentrations of glycogen, primarily in the liver, muscle, or both. MPS is a member of a group of inherited lysosomal storage diseases, which result from a deficiency in specific enzymatic activities and the accumulation of partially degraded acid mucopolysaccharides. A case of a 16-month-old boy who presented with hepatomegaly is reported. The liver was four finger-breadth-palpable. A laboratory study showed slightly increased serum AST and ALT levels. The liver biopsy showed microscopic features compatible with GSD. The liver glycogen content was 9.3% which was increased in comparison with the reference limit, but the glucose-6-phosphatase activity was within the normal limit. These findings suggested GSD other than type I. Bony abnormalities on skeletal radiographs, including an anterior beak and hook-shaped vertebrae, were seen. The mucopolysaccharide concentration in the urine was increased and the plasma iduronate sulfatase activity was low, which fulfilled the diagnosis criteria for Hunter syndrome (MPS type II). To the best of the authors' knowledge, this is the first case of GSD and Hunter syndrome being identified at the same time.

One case of glycogen storage disease complicated with recurrent hepatic adenoma

肝腺瘤是肝脏少见良性肿瘤之一,女性多见,多为单发.糖原累积病(glycogen storage disease,GSD)是一种遗传性疾病,由于糖原代谢过程中某些酶的缺陷从而导致糖原在肝脏或者肌肉等一些组织中累积增加.我科近收治GSD合并复发性多发性肝腺瘤1例,现报告如下。

A Case of Glycogen Storage Disease with Hypertrophic Cardiomyopathy

Glycogen storage diseases are a heterogeneous group of metabolic disorder affecting multiple organ system: liver, skeletal muscle, heart and brain. Clinical features include: short status, hepatomegaly, hypoglycemia, dyslipidemia and rare involvement of the myocardium except in the case of type III, glycogen storage diseases with hypertrophic cardiomyopathy in adult, which is extremely rare. We treated a case of hypertrophic cardiomyopathy with hepatomegaly that was unknown etiology. The patient was diagnosed as having glycogen storage disease. This 46-year old women was transferred with dyspnea on exertion and abnormal LFTs. She was diagnosed with hypertrophic cardiomyopathy by echocardiography but there was no specific cause for hypertrophic cardiomyopathy. A liver biopsy was performed. The result showed glycogen storage disease possible type III, IV or IX. In conclusion, patients with hypertrophic cardiomyopathy of unknown etiology and abnormal LFTs should be evaluated for glycogen storage disease.

CD34 Expression in Hepatocellular Carcinoma and Chronic Liver Diseases

Purpose: Angiogenesis is known to be essential for the progression of hepatocellular carcinoma (HCC). However, the relationship between the occurrence of HCC and angiogenesis has been not elucidated. CD34 have been used for the detection of active angiogenesis in malignant tumors including HCC. Methods: 38 specimens of liver tumor which were obtained from patients including 6 cases of HBV-associated chronic liver diseases, 30 cases of HCV-associated, 1 case of glycogen storage disease, and 1 case of liver disease with unknown etiology by US-guided fine-needle target biopsy were embedded in paraffin, and cut into 4-micrometer-thick sections. These sections were immunostained with anti-CD34 monoclonal antibodies. The standard avidin-biodin-peroxidase complex technique was applied for immunostaining. The CD34 labeling index (LI) was measured. Results: CD34 staining patterns in cases without HCC were all negative or minimal. On the other hand, many of cases with HCC showed focal or diffuse staining pattern. The sensitivity and specificity of focal or diffuse CD34 staining for HCC was 76.9% and 100%. In 72% of cases, we could distinguish HCC from non-HCC area within the same specimen by CD34 staining. In a view of relationship between CD34 staining pattern of obtained tumor tissues and clinical variables of patients, platelet counts was significantly lower in cases with diffuse staining than in cases with negative and minimal staining (p < 0.05). The level of alfa-fetoprotein (AFP) tended to be correlated with the intensity of CD34 staining, and the AFP level of cases with diffuse CD34 staining was significantly higher than that with minimal CD34 staining (p < 0.05). In 34 patients with advanced stages, CD34 LI of 16 patients with progression to HCC within 5 years (HCC group) was significantly higher than that of 18 patients without HCC (non-HCC group)(P = .0199). Moreover, in the same patients, the cumulative incidence of HCC was significantly higher in the patients of CD34 LI≥12 (n = 16) than of CD34 LI<12 (n = 18)(P = .009). Conclusions: These results indicate that evaluating the CD34 expression in chronic liver disease is very useful in predicting the HCC development and diagnosis of HCC.

Pediatric Liver Disease in the Eastern Province of Saudi Arabia: A Clinicopathological Study

This prospective study analyzes the clinical features and histopathological findings in liver biopsies of pediatric patients presenting to the hospital with liver disease during a 10 year period. Only those patients in whom liver biopsy was performed for a tissue diagnosis were included. Fifty patients were investigated, all below the age of 12 years, of whom 36 were male and 14 female. Thirty-two were of neonatal-infantile group, 11 had a diagnosis of neonatal giant cell he hepatitis of infections origin and an intact biliary tree. Two had septic shock and one had leishmaniasis. The remaining 18 patients of the neonatal-infantile group constituted five case of glycogen storage disease, six of infantile obstructive cholangiopathy (biliary atreasia), four of fatty change and one each of congenital hepatic fibrosis, neuroblastoma and nonspecific reactive hepatitis. The eighteen older children had the following diagnoses: thalassemia in five, sickle cell disease in four, two each of Reye syndrome and hepatoblastoma. The remaining were one each of glycogen storage disease, Rotor syndrome, cirrhosis, fatty change and non-Hodgkin lymphoma (NHL). These findings are presented and discussed.

Type I glycogen storage disease with vasoconstrictive pulmonary hypertension

SummaryA case of glycogen storage disease (GSD) type I with vasoconstrictive pulmonary hypertension is described.

Ultrasound findings in childhood chronic liver parenchymal diseases. An analysis of 41 patients.

Forty-one children with liver disease were studied by ultrasound scan at King Khalid University Hospital, Riyadh, Saudi Arabia. Diagnoses were confirmed either by liver biopsy or specific laboratory tests. Sonograms were studied for liver size, beam penetration, echogenicity, vascularity, and biliary tree abnormalities. Different liver diseases, such as chronic hepatitis, biliary cirrhosis, Wilson's disease, familial idiopathic cirrhosis, type III glycogen storage disease, and secondary haemochromatosis revealed non-specific disease patterns. Four cases of biliary cirrhosis and two cases of glycogen storage disease showed periportal fibrosis. Two cases of familial idiopathic cirrhosis and a case of Wilson's disease revealed thickening of the gall bladder wall, which has not been described in the literature.

An unusual case of glycogen storage disease.

Glycogen Storage Disease Type I (G.S.D.I) is characterised by a block in the final common pathway of glucose liberation from the liver leading to abnormal deposition of liver glycogen. The pertinent metabolic features include fasting hypoglycemia, lactic acidemia and increased free fatty acids. A severe tendency towards acidosis, hyperuricemia, hypertriglyceridemia with an abnormal pre- β band are frequently observed. Glucagon administration does not provoke hyperglycemic response, but causes a further rise in blood lactic acid. No hyperglycemic response can be elicited after galactose, fructose or glycerol administration.KeywordsUric AcidGlycogen Storage DiseaseGlycogen Storage Disease TypeGlucagon Stimulation TestBlood Lactic AcidThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Portal diversion for the treatment of glycogen storage disease in humans.

STARZL, THOMAS E. M.D., Ph.D.; PUTNAM, CHARLES W. M.D.; PORTER, KEN A. M.D.; HALGRIMSON, CHARLES C. M.D.; CORMAN, JACQUES M.D.; BROWN, BARBARA I. M.D.; COTLIN, RONALD W. M.D.; RODCERSON, DENIS O. Ph.D.; CREENE, HARRY L. MAJ. MC, USA Author Information

Biochemical and clinical studies on 4 cases of hepatic glycogen storage disease

This report presented 4 cases of glycogen storage diseases. To investigate these cases, the galactose tolerance test, epinephrine test and glucagon double test were performed. Biochemical and enzymological procedures were also employed to tissue samples. Activities of twenty two glycolytic enzymes were determined. Total liver phosphorylase activity was measured by using dephosphophosphorylase kinase. One showed the deficiency of glucose-6-phosphatase (type I, von Gierke). Two showed the deficiency of amylo-1,6-glucosidase (type III, Cori) with the concomitant decrease in glucose-6-phosphatase activity. The last one with hypogonadism demonstrated no glycolytic enzyme defect. In one of type III, hyperglycemic response was demonstrated in each of postprandial epinephrine and glucagon tests in spite of the very low value of glucose-6-phosphatase activity. It was emphasized that differential diagnosis of type of glycogen storage diseases had to be done not only on the results of enzyme assay but also on findings of repeated loading tests.

A case of glycogen storage disease

A case of glycogen storage disease

Cardiomyopathy, cirrhosis of the liver and deposits of a fibrillar polysaccharide: Report of a case with histochemical and electron microscopic studies

Carbohydrate deposits were found in cardiac and smooth muscle fibers, liver, adrenal medulla, sweat gland epithelium and kidneys of a young girl who presented clinical evidence of cardiomyopathy and cirrhosis of the liver. Histochemical and electron microscopic study of the heart showed that the carbohydrate deposits consisted of fine fibrils of a weakly acid polysaccharide. These findings are discussed in relation to the various types of glycogen storage disease and other disorders of carbohydrate metabolism. Polysaccharide storage disease should be considered in atypical cases of glycogen storage disease. Histochemical and electron microscopic study may be necessary to classify properly the diseases associated with the storage of carbohydrate material in the heart and other organs.

INTRODUCTION

SUMMARYAn attempt was made to trace all known or suspected cases of glycogen storage disease in Sweden.1. Totally 35 such cases are discussed; 20 of them could be studied with biochemical and enzymic methods. In an additional 3 patients the diagnosis could be evaluated, since a sib with similar symptoms was investigated. Nine patients were dead without any material having been saved. In three patients, still alive, no new examination could be made.2. Seven of the patients studied were considered to have a definite glycogen storage disease. In 6 of the cases not studied by the author, glycogenosis was considered to be proved by other investigators. Of the 13 patients thus found with definite or highly probable glycogenosis, 8 belonged to type 1 glycogenosis (in 3 cases the type diagnosis is only tentative), 1 (tentatively) to type 2, 1 (tentatively) to type 3 and 2 (1 proved, 1 tentatively) to type 6. In one case no type diagnosis is suggested.1 The criteria for the diagnosis in these 13 cases are discussed.3. In 10 cases studied, it was considered possible to exclude the suspected type or all known types of glycogen storage disease.4. The minimum incidence of known cases of all types of glycogen storage disease in Sweden is calculated to be 1: 246,000 live births.5. The various current diagnostic possibilities are discussed, and the value of clinical, clinical‐chemical, histological, biochemical and enzymic procedures is surveyed. The advantages and drawbacks of modern diagnostic assays on corpuscular elements of the blood are described. It is stressed that these new methods have not made unnecessary the utilization of other diagnostic procedures.

Glucose-6-phosphatase in human jejunal mucosa lack of activity in glycogenosis of cori's type 1

1. (1) The activity of glucose-6-phosphatase (G6Pase) was assayed in human, guinea pig and rat jejunum. A specific G6Pase was indicated in human and guinea pig jejunum but not in that of the rat. 2. (2) Two cases of glycogen storage disease of Con's type 1 were shown completely to lack jejunal G6Pase activity. In spite of this enzyme deficiency they did not have a pathological glycogen storage in the jejunum. 3. (3) It is concluded that human jejunal G6Pase may be governed by the same gene as liver and kidney G6Pase. 4. (4) The importance of the enzyme in human jejunal mucosa is discussed, especially with regard to glucose transport and fructose-to-glucose conversion. 5. (5) Peroral jejunal mucosa biopsy in patients suspected to suffer from von Gierke's disease is judged to be a diagnostic possibility, when liver biopsy cannot be performed.

A chemical investigation of two cases of glycogen storage disease

A chemical investigation of two cases of glycogen storage disease

Glycogen storage disease of the muscles: Report of a case with unusual features

A case of glycogen storage disease of the muscle in a 2 1/2-year-old child is reported. This may represent a fourth type of glycogen disease of striated muscle although, with the data available, a severe form of McArdle's disease with the onset in infancy cannot be excluded. The clinical findings consisted of hypotonia and palatal paralysis without cardiomegaly or hepatomegaly. Blood lactate concentration failed to rise normally following epinephrine administration. Striated muscle contained massive deposits of glycogen of normal molecular structure. Amylo-1, 6-glucosidase was normal. Phosphorylase was not assayed. A summary of the types of glycogen storage disease of muscle is presented. Muscle biopsy in early cases of muscle dystrophy is urged as a means of discovering further examples of glycogen disease of striated muscle.