A patient with glycogen storage disease type Ia combined with chronic hepatitis B infection: a case report.

BACKGROUND: Glycogen storage disease type I (GSD I), also known as von Gierk disease, is a metabolic disorder leading to the excessive accumulation of glycogen and fat in organs, characterized by hepatomegaly, hypoglycemia, lactic acidemia, hyperlipidemia, hyperuricemia, puberty delay and growth retardation, which can be indicated by height, weight, blood glucose and blood lipids. CASE PRESENTATION: Here we present a 16-year-old male patient with GSD Ia complicated with hepatic adenoma and combined with hepatitis B. As a chronic hepatitis B patient, the patient was admitted to hospital in order to further clarify the nature of hepatic space occupancy because of suspicion of hepatocellular carcinoma. However, the imaging studies did not support hepatocellular carcinoma certainly. And by tracing his clinical history, we suggested that he might suffer from GSD I. Finally the diagnosis was confirmed by MRI (Gd-EOB-DTPA), liver biopsy and whole exome sequencing (WES). The WES discovered a homozygous point mutation at the exon 5 of G6PC gene at 17th chromosome, c.G648 T (p.L216 L, NM_000151, rs80356484). This pathogenic mutation causes CTG changing to CTT at protein 216. Though both codons encode leucine, this silent mutation creates a new splicing site 91 bp downstream of the authentic splice site. According to previous research, this mutation is a disease causal variant for GSD Ia, and has a high frequency among GSD patients in China and Japan. This patient was finally diagnosed as GSD Ia complicated with hepatic adenoma and combined with chronic hepatitis B, and received corn starch therapy immediately after GSD was suspected. After receiving corn starch therapy, the height and weight of the patient were increased, and the secondary sexual characteristics were developed, including beard, pubic hair and seminal emission. Unexpectedly, the liver adenomas were still increasing, and we did not find any cause to explain this phenomenon. CONCLUSION: This patient was diagnosed as GSD Ia combined with chronic hepatitis B, who responded to corn starch intervention. For childhood patients with hypoglycaemia, hyperlipidemia, puberty delay and growth retardation, GSD should be considered. Gene sequencing is valuable for the quick identification of GSD subtypes.

Glycemic control and complications in glycogen storage disease type I: Results from the Swiss registry.

BACKGROUND: Regular carbohydrate intake to avoid hypoglycemia is the mainstay of dietary treatment in glycogen storage disease type I (GSDI). The aim of this study was to evaluate the quality of dietary treatment and glycemic control in a cohort of GSDI patients, in relation to the presence of typical long-term complications. METHODS: Data of 25 patients (22 GSD subtype Ia and 3 GSDIb, median age 20y) from the Swiss hepatic glycogen storage disease registry was analyzed cross-sectionally. Frequency and type of hypoglycemia symptoms were assessed prospectively using a structured questionnaire. Diagnostic continuous glucose monitoring (CGM) was performed as part of usual clinical care to assess glycemic control in 14 patients, usually once per year with a mean duration of 6.2 ±â€¯1.1 consecutive days per patient per measurement. RESULTS: Although maintenance of euglycemia is the primary goal of dietary treatment, few patients (n = 3, 13%) performed capillary blood glucose measurements regularly. Symptoms possibly associated with hypoglycemia were present in 13 patients (57%), but CGM revealed periods of low glucose (<4 mmol/l) in all patients, irrespective of the presence of symptoms. GSDIa patients with liver adenomas (n = 9, 41%) showed a higher frequency and area under the curve (AUC) of low blood glucose than patients without adenomas (frequency 2.7 ±â€¯0.8 vs. 1.5 ±â€¯0.7 per day, AUC 0.11 ±â€¯0.08 vs. 0.03 ±â€¯0.02 mmol/l/d; p < 0.05). Similarly, the presence of microalbuminuria was also associated with the frequency of low blood glucose. Z-Scores of bone density correlated negatively with lactate levels. CONCLUSION: The quality of glucose control is related to the presence of typical long-term complications in GSDI. Many patients experience episodes of asymptomatic low blood glucose. Regular assessment of glucose control is an essential element to evaluate the quality of treatment, and increasing the frequency of glucose self-monitoring remains an important goal of patient education and motivation. CGM devices may support patients to optimize dietary therapy in everyday life.

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.

Lipids in hepatic glycogen storage diseases: pathophysiology, monitoring of dietary management and future directions.

Hepatic glycogen storage diseases (GSD) underscore the intimate relationship between carbohydrate and lipid metabolism. The hyperlipidemias in hepatic GSD reflect perturbed intracellular metabolism, providing biomarkers in blood to monitor dietary management. In different types of GSD, hyperlipidemias are of a different origin. Hypertriglyceridemia is most prominent in GSD type Ia and associated with long-term outcome morbidity, like pancreatitis and hepatic adenomas. In the ketotic subtypes of GSD, hypertriglyceridemia reflects the age-dependent fasting intolerance, secondary lipolysis and increased mitochondrial fatty acid oxidation. The role of high protein diets is established for ketotic types of GSD, but non-traditional dietary interventions (like medium-chain triglycerides and the ketogenic diet) in hepatic GSD are still controversial and necessitate further studies. Patients with these rare inherited disorders of carbohydrate metabolism meet several criteria of the metabolic syndrome, therefore close monitoring for cardiovascular diseases in ageing GSD patients may be justified.

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.

Glycogen storage disease type Ia: linkage of glucose, glycogen, lactic acid, triglyceride, and uric acid metabolism.

A female presented in infancy with hypotonia, undetectable serum glucose, lactic acidosis, and triglycerides >5000 mg/dL. The diagnosis of type 1A glycogen storage disease was made via the result of a liver biopsy, which showed increased glycogen and absent glucose-6-phosphatase enzyme activity. The patient was treated with dextrose administered orally, which was replaced by frequent feedings of cornstarch, which resulted in an improvement of her metabolic parameters. At age 18 years of age, she had marked hypertriglyceridemia (3860 mg/dL) and eruptive xanthomas and was treated with fenofibrate, atorvastatin, and fish oil. At age 29 years she was noted to have multiple liver adenomas, severe anemia, and hyperuricemia. Aggressive cornstarch therapy was commenced with a goal of maintaining her blood glucose levels >75 mg/dL and lactate levels <2 mmol/L. After 15 months on this regimen, her lipids levels (measured in mg/dL) off all medications were as follows: total cholesterol 222, triglycerides 179, high-density lipoprotein cholesterol 32, and calculated low-density lipoprotein cholesterol 154. Her weight was stable with a body mass index of 24.8 kg/m(2). Her liver adenomas had decreased in size, and her anemia and hyperuricemia had improved. She was homozygous for the R83C missense mutation in G6PC. Our data indicate that optimized metabolic control to maintain blood glucose levels >75 mg/dL is critical in the management of this disease.

Glucose-6-phosphatase deficiency.

Glucose-6-phosphatase deficiency (G6P deficiency), or glycogen storage disease type I (GSDI), is a group of inherited metabolic diseases, including types Ia and Ib, characterized by poor tolerance to fasting, growth retardation and hepatomegaly resulting from accumulation of glycogen and fat in the liver. Prevalence is unknown and annual incidence is around 1/100,000 births. GSDIa is the more frequent type, representing about 80% of GSDI patients. The disease commonly manifests, between the ages of 3 to 4 months by symptoms of hypoglycemia (tremors, seizures, cyanosis, apnea). Patients have poor tolerance to fasting, marked hepatomegaly, growth retardation (small stature and delayed puberty), generally improved by an appropriate diet, osteopenia and sometimes osteoporosis, full-cheeked round face, enlarged kydneys and platelet dysfunctions leading to frequent epistaxis. In addition, in GSDIb, neutropenia and neutrophil dysfunction are responsible for tendency towards infections, relapsing aphtous gingivostomatitis, and inflammatory bowel disease. Late complications are hepatic (adenomas with rare but possible transformation into hepatocarcinoma) and renal (glomerular hyperfiltration leading to proteinuria and sometimes to renal insufficiency). GSDI is caused by a dysfunction in the G6P system, a key step in the regulation of glycemia. The deficit concerns the catalytic subunit G6P-alpha (type Ia) which is restricted to expression in the liver, kidney and intestine, or the ubiquitously expressed G6P transporter (type Ib). Mutations in the genes G6PC (17q21) and SLC37A4 (11q23) respectively cause GSDIa and Ib. Many mutations have been identified in both genes,. Transmission is autosomal recessive. Diagnosis is based on clinical presentation, on abnormal basal values and absence of hyperglycemic response to glucagon. It can be confirmed by demonstrating a deficient activity of a G6P system component in a liver biopsy. To date, the diagnosis is most commonly confirmed by G6PC (GSDIa) or SLC37A4 (GSDIb) gene analysis, and the indications of liver biopsy to measure G6P activity are getting rarer and rarer. Differential diagnoses include the other GSDs, in particular type III (see this term). However, in GSDIII, glycemia and lactacidemia are high after a meal and low after a fast period (often with a later occurrence than that of type I). Primary liver tumors and Pepper syndrome (hepatic metastases of neuroblastoma) may be evoked but are easily ruled out through clinical and ultrasound data. Antenatal diagnosis is possible through molecular analysis of amniocytes or chorionic villous cells. Pre-implantatory genetic diagnosis may also be discussed. Genetic counseling should be offered to patients and their families. The dietary treatment aims at avoiding hypoglycemia (frequent meals, nocturnal enteral feeding through a nasogastric tube, and later oral addition of uncooked starch) and acidosis (restricted fructose and galactose intake). Liver transplantation, performed on the basis of poor metabolic control and/or hepatocarcinoma, corrects hypoglycemia, but renal involvement may continue to progress and neutropenia is not always corrected in type Ib. Kidney transplantation can be performed in case of severe renal insufficiency. Combined liver-kidney grafts have been performed in a few cases. Prognosis is usually good: late hepatic and renal complications may occur, however, with adapted management, patients have almost normal life span. DISEASE NAME AND SYNONYMS: Glucose-6-phosphatase deficiency or G6P deficiency or glycogen storage disease type I or GSDI or type I glycogenosis or Von Gierke disease or Hepatorenal glycogenosis.

Obesity and reversed growth retardation in a child with type Ia glycogen storage disease.

Type Ia Glycogen storage disease is an autosomal recessive hepatic metabolic disease due to a lack of glucose-6-phosphatase (G-6-Pase) activity presenting with growth retardation, lactic acidosis, fasting hypoglycemia with hypoinsulinemia, hyperuricemia, hepatomegaly, and hepatic adenoma with a risk of malignancy. The gene that encodes G-6-Pase was mapped to 17q21. There are some genotype-phenotype correlations. We report a case with delF327 mutation which is devoid of G-6-Pase activity; however clinical presentation in this case differs somewhat. Although correction of hypoglycemia and lactic acidosis with nocturnal intragastric feeding and uncooked starch therapy improves growth failure, mean height of the patients is often less than the target. Normal height and obesity in this case with hepatic steatosis and low hepatic glycogen storage requires clinical reevaluation since there are some overlapping phenotypes between type Ia GSD and metabolic syndrome. The phenomenon may be related to insulin resistance as a consequence of early aggressive nutrition therapy with frequent low glycemic index meals.

Pregnancies in glycogen storage disease type Ia.

OBJECTIVE: Reports on pregnancies in women with glycogen storage disease type Ia (GSD-Ia) are scarce. Because of improved life expectancy, pregnancy is becoming an important issue. We describe 15 pregnancies by focusing on dietary treatment, biochemical parameters, and GSD-Ia complications. STUDY DESIGN: Carbohydrate requirements (milligrams per kilogram per minute), triglyceride and uric acid levels, liver ultrasonography, and creatinine clearance were investigated before, during, and after pregnancy. Data from the newborn infants were obtained from the records. RESULTS: In the first trimester, a significant increase in carbohydrate requirements was observed (P = .007). Most patients had acceptable triglyceride and uric acid levels during pregnancy. No increase in size or number of adenomas was seen. In 3 of 4 patients, a decrease in glomerular filtration rate was observed after pregnancy. In 3 pregnancies, lactic acidosis developed during delivery with severe multiorgan failure in 1. All but 1 of the children are healthy and show good psychomotor development. CONCLUSION: Successful pregnancies are possible in patients with GSD-Ia, although specific GSD-Ia-related risks are present.

Effect of continuous glucose therapy with uncooked cornstarch on the long-term clinical course of type 1a glycogen storage disease.

UNLABELLED: To evaluate the effects of uncooked cornstarch (UCS) on metabolic control, growth, and complications of pubertal and postpubertal subjects with type 1a glycogen storage disease, we studied 26 subjects (16 males), mean age 20.8+/-5.1 years, in whom continuous glucose therapy with cornstarch began at 6.8+/-4.3 years. At the time of this analysis, subjects had received cornstarch for 14.1+/-3.5 years. Metabolic control was determined with subjects receiving their usual home dietary regimens: 4.1+/-1.3 doses of UCS in the day (9.7+/-2.6 g/h) and 2.0+/-0.4 doses at night (11.7+/-2.2 g/h). Mean height standard deviation score (SDS) was -1.2+/-1.3, significantly less than the mean target height of -0.2+/-1.1 ( P<0.01). Mean weight SDS was 0.5+/-1.9 and body mass index SDS was 0.7+/-1.0. Of all subjects, 50% had at least one focal hepatic lesion consistent with an adenoma. Urinary albumin excretion was increased (>20 micro g/min) in 31% of subjects; two subjects had clinical albuminuria (>300 mg per 24 h), but none has progressed to chronic renal insufficiency. Of 26 subjects, 13 (50%) had anemia. All of the complications were associated with evidence of suboptimal metabolic control, whereas subjects with no evidence of any long-term complications had near normal blood lactate and total CO(2) concentrations. CONCLUSION: The achievement of optimal biochemical control of glycogen storage disease type 1a continues to be a challenge, but is attainable by meticulous adherence to an individualized dietary regimen based on the results of periodic metabolic evaluation and home blood glucose monitoring. Minimizing the metabolic abnormalities of the disease may decrease the risk of long-term complications.

Type I glycogen storage disease: favourable outcome on a strict management regimen avoiding increased lactate production during childhood and adolescence.

UNLABELLED: Our objective was to evaluate the long-term effects of dietary therapy of type I glycogen storage disease which avoids increased lactate production during childhood and adolescence. In order to suppress hepatic glucose and increased lactate production consistently day and night, the treatment regimen included nocturnal intragastric feeding of glucose polymer during childhood and adolescence. The aim was to keep the blood glucose concentration in the "high normal range" (4.3-5.5 mmol/l) and the lactate concentration in urine in the normal range (<0.06 mol/mol creatinine). The amounts of dietary carbohydrate required decreased in an age-related manner from 11.9+/-1.3 mg/kg body weight per min by day and 6.9+/-0.9 mg/kg body weight per min by night at 1 year of age to 5.2+/-1.0 and 2.9+/-1.2 mg/kg body weight per min, respectively, at the age of 16 years. In 15 infants, therapy started at 5.8+/-3.2 months of age and induced catch up growth over 1-2 years by which time the mean height SDS increased from -1.02+/-0.91 to -0.19+/-1.07. In the well controlled patients, further growth continued within that range. From 12 years of age, mean height SDS was in line with the respective mean SDS of mid-parental target height. The plasma lipid concentrations were markedly reduced, but were not brought into the normal range. So far, no adolescent showed liver adenoma or renal damage. Four patients with poor metabolic control due to poor compliance with treatment (frequently subnormal plasma glucose concentrations, severe hypoglycaemia, and increased urinary lactate excretion) showed retardation of growth and bone maturation. CONCLUSION: avoiding increased lactate production by keeping the blood glucose concentration permanently in the "high normal range" seems to be crucial for growth according to the genetic potential.

Guidelines for management of glycogen storage disease type I - European Study on Glycogen Storage Disease Type I (ESGSD I).

UNLABELLED: Life-expectancy in glycogen storage disease type I (GSD I) has improved considerably. Its relative rarity implies that no metabolic centre has experience of large series of patients and experience with long-term management and follow-up at each centre is limited. There is wide variation in methods of dietary and pharmacological treatment. Based on the data of the European Study on Glycogen Storage Disease Type I, discussions within this study group, discussions with the participants of the international SHS-symposium 'Glycogen Storage Disease Type I and II: Recent Developments, Management and Outcome' (Fulda, Germany; 22-25th November 2000) and on data from the literature, guidelines are presented concerning: (1). diagnosis, prenatal diagnosis and carrier detection; (2). (biomedical) targets; (3). recommendations for dietary treatment; (4). recommendations for pharmacological treatment; (5). metabolic derangement/intercurrent infections/emergency treatment/preparation elective surgery; and (6). management of complications (directly) related to metabolic disturbances and complications which may develop with ageing and their follow-up. CONCLUSION: In this paper guidelines for the management of GSD I are presented.

Long-term follow-up of portacaval shunt in glycogen storage disease type 1B.

UNLABELLED: In two girls with glycogen storage disease (GSD) type 1b, terminolateral portacaval shunt (PCS) with partial circular resection of the lobus quadratus of the liver was performed at the age of 12 and 10 years, respectively. At that time, the patients had a height of -3.1 and -1.7 SDS, respectively. PCS resulted in a spectacular growth spurt of 35 cm within the first 5 years after surgery in both of them. As first sign of puberty, breast enlargement started 2.5 years after PCS in both patients. Improved glucose tolerance was evidenced by increased levels of blood glucose and insulin after PCS. Diet with raw cornstarch (CS), 2g/kg body weight four times daily, was started 8 years after PCS in patient 1, but initiated with nightly gastric feeding at the age of 2 years in patient 2, 8 years before PCS. Treatment with recombinant granulocyte colony-stimulating factor (rhGCSF), 6 microg/kg body weight every 36-48 h, was started 20 years after PCS in patient 1, but only 1 month before PCS in patient 2. Progressive development of up to 7-8 liver adenomas was observed after PCS, but without conclusive signs of malignancy on Ferrit MRI. The PCS is still open 23 and 7 years after PCS, respectively. Terminolateral PCS with partial circular resection of the lobus quadratus of the liver associated with dietary control and rhGCSF might still have a place in the treatment of GSD type 1b because it improves the tolerance to fasting and the quality of life and moreover yields excellent metabolic control. CONCLUSION: Treatment of glycogen storage disease type 1b by portacaval shunt might be considered in patients with height-for-age below the 3rd percentile occurring in spite of dietary control, or before considering liver transplantation which, if necessary, can still be performed after shunt surgery.

Liver transplantation for glycogen storage disease types I, III, and IV.

UNLABELLED: Glycogen storage disease (GSD) types I, III, and IV can be associated with severe liver disease. The possible development of hepatocellular carcinoma and/or hepatic failure make these GSDs potential candidates for liver transplantation. Early diagnosis and initiation of effective dietary therapy have dramatically improved the outcome of GSD type I by reducing the incidence of liver adenoma and renal insufficiency. Nine type I and 3 type III patients have received liver transplants because of poor metabolic control, multiple liver adenomas, or progressive liver failure. Metabolic abnormalities were corrected in all GSD type I and type III patients, while catch-up growth was reported only in two patients. Whether liver transplantation results in reversal and/or prevention of renal disease remains unclear. Neutropenia persisted in both GSDIb patients post liver transplantation necessitating continuous granulocyte colony stimulating factor treatment. Thirteen GSD type IV patients were liver transplanted because of progressive liver cirrhosis and failure. All but one patient have not had neuromuscular or cardiac complications during follow-up periods for as long as 13 years. Four have died within a week and 5 years after transplantation. Caution should be taken in selecting GSD type IV candidates for liver transplantation because of the variable phenotype, which may include life-limiting extrahepatic manifestations. It remains to be evaluated, whether a genotype-phenotype correlation exists for GSD type IV, which may aid in the decision making. CONCLUSION: Liver transplantation should be considered for patients with glycogen storage disease who have developed liver malignancy or hepatic failure, and for type IV patients with the classical and progressive hepatic form.

Effect of continuous glucose therapy begun in infancy on the long-term clinical course of patients with type I glycogen storage disease.

BACKGROUND: To evaluate the effects of continuous glucose therapy on metabolic control, occurrence of severe hypoglycemia, physical growth and development, and complications of glycogen storage disease type I (GSD-I). METHODS: Seventeen patients (11 males) with GSD-I were studied, mean age 14.6+/-5.0 (SD) years, in whom continuous glucose therapy was begun at 0.8+/-0.4 years. At the time of this study, subjects had received continuous glucose therapy for a total duration of 13.9+/-5.0 years. Uncooked cornstarch was used as the method of providing glucose continuously for 10.2+/-3.2 years. Subjects were admitted to the Clinical Research Center and followed their usual home dietary regimens, which included cornstarch supplements at 2- to 4-hour intervals during the day and at 4- to 8-hour intervals during the night. Plasma glucose, blood lactate, and glucoregulatory hormones were measured hourly for 24 hours. RESULTS: During a 24-hour period of biochemical monitoring, mean hourly plasma glucose concentrations for the group of 17 subjects ranged from 76+/-17 (SD) mg/dl (4.2+/-0.9 mmol/l) to 108+/-16 mg/dl (6.0+/-0.9 mmol/l), and blood lactate concentrations ranged from 2.1+/-1.2 mmol/l to 3.8+/-2.8 mmol/l. Four subjects had transient plasma glucose levels of 50 mg/dl (2.8 mmol/l) or less in the interval between midnight and 8:00 AM. Mean blood lactate levels were highest (> or =3 mmol/l) between 2:00 and 09:00 AM. Mean height standard deviation score for chronological age (SDS(CA)) was -0.8+/-1.1, significantly (p < 0.01) less than the mean target height SDS of -0.1+/-1.1; mean weight SDS was 0.3+/-1.3. Six (35%) subjects (12.2-21.4 years of age) had anemia with hemoglobin concentrations of 10.6 to 11.6 g/dl. Ultrasound examination showed one or more focal hepatic lesions, consistent with an adenoma in 5 (29%) subjects (10.4 to 21.4 y); 16 subjects had glomerular hyperfiltration; and urinary albumin excretion was increased in 2 subjects, ages 15.9 and 21.1 years. CONCLUSIONS: Long-term continuous glucose therapy with cornstarch, begun in infancy, resulted in mean height 0.7 SDS less than target height. Optimal biochemical control of GSD-I requires meticulous adherence to an individualized dietary regimen that is based on the results of periodic metabolic evaluation and home blood glucose monitoring. Renal glomerular dysfunction and formation of hepatic adenomata remain serious long-term complications.

[Corn starch in the treatment of patients with glycogenosis type I and III]. / Almidón de maíz crudo en el tratamiento de pacientes con glucogenosis tipo I y III.

RATIONALE: Administering raw corn starch can maintain normoglycemia for long periods after being ingested, thus facilitating control in patients with type I and III glycogenosis. METHODS: The metabolic effects and the effects on the nutritional status of a treatment with fractionated administrations of raw starch are assessed in two patients with type I glycogenosis (ages 18 and 12 years) and one patient with type III glycogenosis (aged 13 years). In the first two cases the response was previously studied after administering a load of raw corn starch in a water suspension, in an amount similar to the estimated rate of endogenous glucose production during the fasting period (5 mg/kg/minute). RESULTS: The results of the overload of starch showed a normoglycemia and an absence of lactoacidosis between 4 and 6 hours after its ingestion. The three patients were given two doses of raw corn starch (2 g/kg/dose) at 1.00 and 5.00 hours during the night. After one year of treatment, all patients showed glycemia levels at 9.00 AM that were greater than 90 mg/dl and lactic acid levels that were lower than 2.4 mmol/l. Moreover, in two of the cases there was an increase in the growth rate. In all cases the amount of the hepatomegaly decreased as did the size of the hepatic adenomas that were present in two of the cases. CONCLUSIONS: In patients with type I and III glycogenosis, raw corn starch can balance the results of the nightly gastric glucose infusion, both with regard to the metabolic control and with regard to the growth.

Three consecutive pregnancies in a patient with glycogen storage disease type IA (von Gierke's disease).

Glycogen storage disease type IA is associated with metabolic abnormalities that can compromise fetal outcome. Normal outcome can be achieved by maintaining euglycemia throughout gestation. We report three consecutive pregnancies in a patient with glycogen storage disease type IA. The patient, a 35-year-old woman, has been maintained on a regimen of nightly nasogastric or cornstarch feedings for the past 12 years with improving metabolic control, reduced liver size, and no progression of multiple hepatic adenomas. On confirmation of each pregnancy, early in the first trimester nightly feeding was changed from cornstarch ingestion to Polycose by nasogastric intubation, with good metabolic control. During the last trimester of each pregnancy metabolic control showed further improvement, with lowering of lactate, urate, and triglyceride levels. During the first pregnancy unexpected fetal death occurred at 33 weeks. During the last two pregnancies, the patient was admitted at 33 and 34 weeks, respectively, for closer supervision of metabolic status and fetal monitoring. She underwent a cesarean section at 35 weeks 4 days of gestation and was delivered of a girl. She underwent a repeat cesarean section at 35 weeks 2 days for the subsequent gestation and was delivered of a boy. Both infants are healthy and appear to be unaffected by von Gierke's disease. Hepatic adenomas did not enlarge during the pregnancies. Meticulous management resulted in normal pregnancy outcomes in two consecutive gestations. Rapid fetal growth late in the third trimester may require particularly careful supervision to maintain euglycemia.