Successful Anesthetic Management of an Adult Patient With Glycogen Storage Disease Type 1 During Liver Transplant: A Case Report.

Glycogen storage disease type 1 is a congenital abnormality of metabolism caused by the deficiency of the glucose-6-phosphatase enzyme, essential in glucose homeostasis. Patients with this disease are at high risk of developing hypoglycemia, hyperlipidemia, lactic acidemia, growth retardation, neutropenia, inflammatory bowel disease, and many other severe complications, such as hepatic adenomas converting into hepatocellular carcinomas. To prevent these complications, a liver transplant is the ultimate method of treatment. We present the successful anesthesia management for a 21-year-old man who had gross hepatomegaly, severe hypoglycemia, and hyperlactatemia and who received a liver transplant from his mother, which is a substantial challenge for anesthesiologists. Anesthesiologists should know the underlying pathophysiological condition and perform a comprehensive preoperative evaluation to determine the correct anesthesia plan in patients with glycogen storage disease type 1 who will undergo an orthotopic liver transplant due to multiple system disorders. Successful perioperative management of patients with glycogen storage disease type 1 relies on effective communication and collaboration between specialists through a multidisciplinary team approach.

Previously undiagnosed genetic disease in adult patient with hepatic masses and reported history of congenital hyperinsulinism.

Glycogen storage disease type 1A (GSD1A), also known as Von Gierke's disease, is a rare autosomal recessive disorder affecting glycogen metabolism in the liver. It most commonly presents in infancy with hypoglycaemia and failure to thrive, but cases have been reported as undiagnosed until adulthood. A woman in her early 20s with diabetes mellitus presented with right upper quadrant pain and was found to have several haemorrhagic hepatic adenomas. This patient had insulin-dependent diabetes since a pancreatectomy at age 9 months due to continued episodes of hypoglycaemia and suspected insulinoma. During the hospital stay, the hepatic adenomas were embolised, but significant lactic acidosis and hypoglycaemia continued. Further workup revealed a chronic lactic acid level, during several hospital stays, of above 5 mmol/L. After cytology of hepatic tissue ruled out hepatocellular carcinoma, the patient was discharged and recommended to follow-up for genetic testing, which confirmed the diagnosis of GSD1A.

Report of an Iranian child with chronic abdominal pain and constipation diagnosed as glycogen storage disease type IX: a case report.

BACKGROUND: Glycogen storage disease type IX is a rare disorder that can cause a wide variety of symptoms depending on the specific deficiency of the phosphorylase kinase enzyme and the organs it affects. CASE PRESENTATION: A 4-and-a-half-year-old Caucasian girl was referred to our clinic with a liver biopsy report indicating a diagnosis of glycogen storage disease. Prior to being referred to our clinic, the patient had been under the care of pediatric gastroenterologists. The patient's initial symptoms included chronic abdominal pain, constipation, and elevated liver transaminase. With the help of the pediatric gastroenterologists, cholestasis, Wilson disease, and autoimmune hepatitis were ruled out. Given that glycogen storage diseases type I and type III are the most common, we initially managed the patient with frequent feedings and a diet that included complex carbohydrates such as a corn starch supplement and a lactose restriction. Following an unfavorable growth velocity and hepatomegaly during the follow-up period, genetic analysis was conducted, which revealed a novel mutation of the phosphorylase kinase regulatory subunit beta gene- a c.C412T (P.Q138x) mutation. As the diagnosis of glycogen storage disease type IX was confirmed, the treatment regimen was altered to a high protein diet (more than 2 g/kg/day) and a low fat diet. CONCLUSION: Given the mild and varied clinical manifestations of glycogen storage disease type IX, it is possible for the diagnosis to be overlooked. It is important to consider glycogen storage disease type IX in children who present with unexplained hepatomegaly and elevated transaminase levels. Furthermore, due to the distinct management of glycogen storage disease type IX compared with glycogen storage disease type I and glycogen storage disease type III, genetic analysis is essential for an accurate diagnosis.

A case of glycogen storage disease type â a with gout as the first manifestation. / 以痛风为首发的糖原贮积症â a型一例.

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.

Persistent acidosis and chronic kidney disease in a patient with type 1 glycogen storage disease.

Type 1 glycogen storage disease (GSDI) is a rare autosomal recessive disorder caused by glucose-6-phosphatase (G6Pase) deficiency. We discuss a case of a 29-year-old gentleman who had GSDI with metabolic complications of hypoglycemia, hypertriglyceridemia, hyperuricemia, and short stature. He also suffered from advanced chronic kidney disease, nephrotic range proteinuria, and hepatic adenomas. He presented with acute pneumonia and refractory metabolic acidosis despite treatment with isotonic bicarbonate infusion, reversal of hypoglycemia, and lactic acidosis. He eventually required kidney replacement therapy. The case report highlights the multiple contributing mechanisms and challenges to managing refractory metabolic acidosis in a patient with GSDI. Important considerations for dialysis initiation, decision for long-term dialysis modality and kidney transplantation for patients with GSDI are also discussed in this case report.

First report of suspected glycogen storage disease type 1a occurring in an adult dog.

A 4-year-old female border collie was presented with haemoabdomen following the rupture of a hepatocellular carcinoma. After referral for ongoing elevation of alanine aminotransferase and alkaline phosphatase, the dog was found to have marked vacuolar hepatopathy due to glycogen accumulation within the liver, fasting hypoglycaemia and hyperlactataemia, and a negative response to glucagon stimulation testing. These changes were strongly suggestive of glycogen storage disease type 1a. Based on our literature search, this report documents the first adult canine to be diagnosed with suspected glycogen storage disease type 1a.

Glycogen Storage Disease Type Ia Screening Using Dried Blood Spots on Filter Paper: Application of COP-PCR for Detection of the c.648G>T G6PC Gene Mutation.

Glycogen storage disease type Ia (GSDIa, OMIM #232200) is an autosomal recessive metabolic disease characterized by impaired glucose homeostasis and has a long-term complication of hepatocellular adenoma/carcinoma. GSDIa is caused by deleterious mutations in the glucose-6-phosphatase gene (G6PC). Recent studies have suggested that early treatment by gene replacement therapy may be a good solution to correct the glucose metabolism and prevent serious late complications. Early treatment of the disease needs an early disease detection system. Thus, we aimed to develop a screening system for GSDIa using dried blood spots (DBS) to detect the c.648G>T mutation in G6PC, which is a frequent mutation in the East Asian population. In this study, a total of 51 DBS samples (50 healthy controls and one patient with c.648G>T) were tested by modified competitive oligonucleotide priming PCR (mCOP-PCR). In control DBS samples, the c.648G allele was amplified at lower Cq (quantification cycle) values (<11), while the c.648T allele was amplified at higher Cq values (>14). In the patient DBS sample, the c.648T allele was amplified at a lower Cq value (<11), and the c.648G allele was amplified at a higher Cq value (>14). Based on these findings, we concluded that our mCOP-PCR system clearly differentiated the wild-type and mutant alleles, and may be applicable for screening for GSDIa with the c.648G>T mutation in G6PC.

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.

[Glycogen storage disease type â a: a rare cause of gout in adolescent and young adult patients].

Objective: To analyze the clinical features of secondary gout in glycogen storage disease type Ⅰa (GSD Ⅰa), so as to improve the awareness of this disease. Methods: The clinical features, laboratory findings, treatments and prognosis of 5 GSD Ⅰa patients with secondary gout who had been admitted to the Peking Union Medical College Hospital during 2006 to 2016 were collected and analyzed. GSD Ⅰa was confirmed by liver biopsy and genotyping. Results: Among the 5 patients (median age: 27 years), 3 were males and 2 were females. The mean age of gout onset was 17 ranging from 10 to 22 years old. The common manifestations of GSD included hepatomegaly since childhood, hypoglycemia, growth retardation, anemia, hyperlactacidemia and hyperlipidemia. All the 5 patients were complicated with gouty tophi and kidney stone. Gouty tophi and kidney stone were identified 3.8 years and 10.2 years after the first occurrence of articular symptoms, respectively. Renal damage occurred in 3 cases. All the patients underwent several therapeutic modalities including lifestyle intervention, allopurinol, and raw corn starch treatment. Conclusions: Determination of the presence of primary disease should be performed actively for young-onset gout with early occurrence of gouty tophi. GSD should be suspected if there exist clinical manifestations like hepatomegaly, recurrent hypoglycemia, growth retardation. Early management of hyperuricemia and gout in GSD patients is important to prevent complications and improve prognosis.

Prevention of complications in glycogen storage disease type Ia with optimization of metabolic control.

Prior to 1971, type Ia glycogen storage disease was marked by life-threatening hypoglycemia, lactic acidosis, severe failure to thrive, and developmental delay. With the introduction of continuous feeds in the 1970s and cornstarch in the 1980s, the prognosis improved, but complications almost universally developed. Changes in the management of type Ia glycogen storage disease have resulted in improved metabolic control, and this manuscript reviews the increasing evidence that complications can be delayed or prevented with optimal metabolic control as previously was seen in diabetes.

Reappraisal of the Role of Portacaval Shunting in the Growth of Patients With Glycogen Storage Disease Type I in the Era of Liver Transplantation.

BACKGROUND: Instead of dietary modification, surgical management is considered for correcting growth retardation, poor metabolic control, and hepatocellular adenoma (HCA) in glycogen storage disease (GSD) type I. METHODS: The records of 55 GSD type I patients were retrospectively reviewed. Thirty-two patients underwent only dietary management (group D) and 23 underwent surgical management (group S). In group S, 17 underwent portacaval shunting (PCS), 13 underwent liver transplantation (LT; 7 underwent both PCS and LT). Height-for-age and body mass index-for-age Z-scores based on World Health Organization data were used to compare growth patterns before and after surgery. Changes in metabolic abnormalities and HCA after operation were also investigated. RESULTS: Height-for-age Z-scores for group S were higher by an average of 0.377 compared to that for group D. Metabolic abnormalities often disappeared after LT but improved partially after PCS. De novo HCA was detected in 4 patients (13%) from group D, 12 (100%) who underwent PCS, and none who underwent LT. One case of hepatocellular carcinoma and one of hemorrhage from a HCA were noted in group D. Two cases of hepatocellular carcinoma, 2 of hemorrhage, and 1 of necrosis were noted after PCS. CONCLUSIONS: Surgery yielded greater growth improvement than dietary management. However, after PCS, metabolic abnormalities remained unresolved, and the de novo HCA rate was high. Portacaval shunting can be used to improve growth in GSD type I patients when LT is not possible, but close observation for metabolic abnormalities and HCA is essential.

Hepatic glycogen storage disorders: what have we learned in recent years?

PURPOSE OF REVIEW: Glycogen storage disorders (GSDs) are inborn errors of metabolism with abnormal storage or utilization of glycogen. The present review focuses on recent advances in hepatic GSD types I, III and VI/IX, with emphasis on clinical aspects and treatment. RECENT FINDINGS: Evidence accumulates that poor metabolic control is a risk factor for the development of long-term complications, such as liver adenomas, low bone density/osteoporosis, and kidney disease in GSD I. However, mechanisms leading to these complications remain poorly understood and are being investigated. Molecular causes underlying neutropenia and neutrophil dysfunction in GSD I have been elucidated. Case series provide new insights into the natural course and outcome of GSD types VI and IX. For GSD III, a high protein/fat diet has been reported to improve (cardio)myopathy, but the beneficial effect of this dietary concept on muscle and liver disease manifestations needs to be further established in prospective studies. SUMMARY: Although further knowledge has been gained regarding pathophysiology, disease course, treatment, and complications of hepatic GSDs, more controlled prospective studies are needed to assess effects of different dietary and medical treatment options on long-term outcome and quality of life.

Glycogen storage disease type I: clinical and laboratory profile / Doença de depósito de glicogênio tipo I: perfil clínico e laboratorial

OBJECTIVES: To characterize the clinical, laboratory, and anthropometric profile of a sample of Brazilian patients with glycogen storage disease type I managed at an outpatient referral clinic for inborn errors of metabolism. METHODS: This was a cross-sectional outpatient study based on a convenience sampling strategy. Data on diagnosis, management, anthropometric parameters, and follow-up were assessed. RESULTS: Twenty-one patients were included (median age 10 years, range 1-25 years), all using uncooked cornstarch therapy. Median age at diagnosis was 7 months (range, 1-132 months), and 19 patients underwent liver biopsy for diagnostic confirmation. Overweight, short stature, hepatomegaly, and liver nodules were present in 16 of 21, four of 21, nine of 14, and three of 14 patients, respectively. A correlation was found between height-for-age and BMI-for-age Z-scores (r = 0.561; p = 0.008). CONCLUSIONS: Diagnosis of glycogen storage disease type I is delayed in Brazil. Most patients undergo liver biopsy for diagnostic confirmation, even though the combination of a characteristic clinical presentation and molecular methods can provide a definitive diagnosis in a less invasive manner. Obesity is a side effect of cornstarch therapy, and appears to be associated with growth in these patients. .

OBJETIVOS: Caracterizar o perfil clínico, laboratorial e antropométrico de uma amostra de pacientes brasileiros com doença de depósito de glicogênio tipo I tratados em um ambulatório de referência para erros inatos do metabolismo. MÉTODOS: Este foi um estudo ambulatorial transversal com base em uma estratégia de amostragem de conveniência. Foram avaliados os dados com relação ao diagnóstico, tratamento, parâmetros antropométricos e acompanhamento. RESULTADOS: Foram incluídos 21 pacientes (idade média de 10 anos, faixa 1-25 anos de idade), e todos se encontravam em terapia de amido de milho cru. A idade média na época do diagnóstico foi de sete meses (faixa, 1-32 meses), e 19 pacientes foram submetidos a biópsia hepática para confirmação do diagnóstico. Sobrepeso, baixa estatura, hepatomegalia e nódulos hepáticos foram fatores presentes em 16 de 21, quatro de 21, nove de 14 e três de 14 pacientes, respectivamente. Foi encontrada uma correlação entre os escores z para peso para idade e IMC para idade (r = 0,561; p = 0,008). CONCLUSÕES: O diagnóstico da doença de depósito de glicogênio tipo I tem sido tardio no Brasil. A maioria dos pacientes foi submetida a confirmação do diagnóstico, apesar de o quadro clínico característico e os métodos moleculares poderem fornecer um diagnóstico definitivo de forma menos invasiva. Obesidade é um efeito colateral da terapia com amido de milho e parece estar associada a crescimento nesses pacientes. .

Glycogen storage disease type I: clinical and laboratory profile.

OBJECTIVES: To characterize the clinical, laboratory, and anthropometric profile of a sample of Brazilian patients with glycogen storage disease type I managed at an outpatient referral clinic for inborn errors of metabolism. METHODS: This was a cross-sectional outpatient study based on a convenience sampling strategy. Data on diagnosis, management, anthropometric parameters, and follow-up were assessed. RESULTS: Twenty-one patients were included (median age 10 years, range 1-25 years), all using uncooked cornstarch therapy. Median age at diagnosis was 7 months (range, 1-132 months), and 19 patients underwent liver biopsy for diagnostic confirmation. Overweight, short stature, hepatomegaly, and liver nodules were present in 16 of 21, four of 21, nine of 14, and three of 14 patients, respectively. A correlation was found between height-for-age and BMI-for-age Z-scores (r=0.561; p=0.008). CONCLUSIONS: Diagnosis of glycogen storage disease type I is delayed in Brazil. Most patients undergo liver biopsy for diagnostic confirmation, even though the combination of a characteristic clinical presentation and molecular methods can provide a definitive diagnosis in a less invasive manner. Obesity is a side effect of cornstarch therapy, and appears to be associated with growth in these patients.

PCR-based allelic discrimination for glucose-6-phosphate dehydrogenase (G6PD) deficiency in Ugandan umbilical cord blood.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common X-linked disorder in the world. G6PD deficiency puts children at risk for hyperbilirubinemia and kernicterus during the newborn period and an increased risk of severe hemolysis after exposure to many antimalarial medications. A laboratory diagnosis of G6PD deficiency is rare in the developing world due to limited resources. We developed a TaqMan-based allele-specific assay to rapidly determine rates of G6PD deficiency contributing alleles (G202A and A376G) in East Africa. We tested umbilical cord blood from 100 Ugandan newborns and found that the overall allele frequency of G202A was .13 and A376G was .32. The overall incidence of G6PD A- (G202A/A376G) was 6%; all A- variants were males. There was no correlation between G6PD deficiency and umbilical cord blood hemoglobin, white blood count, platelet count, or other hematologic parameters. Allele-specific PCR can serve as a rapid method to determine specific G6PD deficiency allele frequencies in a given population and as a diagnostic tool in a hospital setting in which laboratory resources are present.

Rapid molecular diagnosis of genetic diseases by high resolution melting analysis: fabry and glycogen storage 1A diseases.

For inborn errors of metabolism, high resolution melting analysis (HRMA) is a rapid, efficient, simple, and inexpensive method for mutation/rare variant screening. HRMA is a recent molecular technique for genotyping single-nucleotide polymorphisms without using probes. Here we apply HRMA to the α-galactosidase a (GLA) and glucose-6-phosphatase-alpha (G6PC) genes for mutation detection of patients with Fabry disease (MIM 301500) and glycogen storage disease type 1A (GSD1A; MIM 232200), respectively. To evaluate the procedure, genomic DNAs were blindly tested for known GLA mutations (c.658C>T, c. 679C>T, c.772G>A, c.796G>A, or c.718-719delAA) in three affected males and two obligate heterozygotes with Fabry disease, a G6PC mutation (c.247C>T) in a patient homozygous for that lesion, and 10 healthy control Turkish individuals. HRMA clearly detected the mutant amplicons and discriminated them from all wild-type GLA or G6PC amplicons. HRMA proved to be a sensitive, specific, and cost-effective mutation screening method for the rapid molecular diagnosis of these inborn errors of metabolism, indicating that the technique can be readily adapted to other genetic diseases.

[History case of multiple hepatic adenomas in adolescent with severe course of glycogen storage disease type lb].

We represented a case history of multiple hepatic adenomas in an adolescent with severe clinical course of glycogen storage disease type lb (compound heterozygous mutations c.1042_1043delCT and c.817G>A in the SLC37A4). The patient was prescribed a raw cornstarch and hepatoprotectors therapy, but he and his parents had low compliance to treatment. At the age of 13,5 years ultrasound investigation and computed tomography revealed multiple adenomas. Due to the severe condition of the patient it was impossible to perform focal hepatic biopsy. At present time the patient receives treatment focused on correction of metabolic disturbances, thereafter an applicability of exploratory puncture will be settled for the further patient surveillance. The modern data on causes and risk factors of hepatic adenomas in such patients, the possibility of their malignization, the algorithm of the follow-up and the methods of treatment are presented in the discussion.

Fifteen years of follow-up of a liver transplant recipient with glycogen storage disease type Ia (Von Gierke disease).

Von Gierke's disease or glycogen storage disease type Ia (GSD-Ia) is an infrequent metabolic disease caused by an atypical accumulation of glycogen. The principal cause of this pathology is deficiency of the glucose-6-phosphatase enzyme. Herein we have reported a case of a young man with a history of Von Gierke's disease (GSD-Ia) since childhood who developed hepatocellular adenomatosis brought to light by ultrasounds and TACs. The patient began to develop early chronic renal failure, necessitating simultaneous liver and kidney transplantation. Years later continuous reviews at the nephrology and hepatobiliopancreatic surgery services show he has a good quality of life and a normal hepatorenal profile.