Pulmonary hypertension in type I glycogen storage disease

Summary Two cases of pulmonary hypertension associated with type I glycogen storage disease (type I GSD) are reported. Before the development of pulmonary hypertension, patient 1 had been treated with dietary therapy with nocturnal gastric-drip infusion and zyloric therapy. Patient 2 had received a shunt operation between the intestinal vein and inferior vena cava, as well as dietary therapy. Both patients died of progressive heart failure due to pulmonary hypertension despite many attempts at drug therapy. There was no evidence in either case of a disorder that could have been the cause of the pulmonary hypertension. In case 1, the autopsy revealed a vascoconstrictive type of pulmonary hypertension with plexiform vascular lesions.     

Liver transplantation for type I and type IV glycogen storage disease

Progressive liver failure or hepatic complications of the primary disease led to orthotopic liver transplantation in eight children with glycogen storage disease over a 9-year period. One patient had glycogen storage disease (GSD) type I (von Gierke disease) and seven patients had type IV GSD (Andersen disease). As previously reported [19], a 16.5-year-old-girl with GSD type I was successfully treated in 1982 by orthotopic liver transplantation under cyclosporine and steroid immunosuppression. The metabolic consequences of the disease have been eliminated, the renal function and size have remained normal, and the patient has lived a normal young adult life. A late portal venous thrombosis was treated successfully with a distal splenorenal shunt. Orthotopic liver transplantation was performed in seven children with type N GSD who had progressive hepatic failure. Two patients died early from technical complications. The other five have no evidence of recurrent hepatic amylopectinosis after 1.1–5.8 postoperative years. They have had good physical and intellectual maturation. Amylopectin was found in many extrahepatic tissues prior to surgery, but cardiopathy and skeletal myopathy have not developed after transplantation. Post-operative heart biopsies from patients showed either minimal amylopectin deposits as long as 4.5 years following transplantation or a dramatic reduction in sequential biopsies from one patient who initially had dense myocardial deposits. Serious hepatic derangement is seen most commonly in types I and IV GSD. Liver transplantation cures the hepatic manifestations of both types. The extrahepatic deposition of abnormal glycogen appears not to be problematic in type I disease, and while potentially more threatening in type IV disease, may actually exhibit signs of regression after hepatic allografting.     

Pulmonary vascular disease in a child with atrial septal defect of the secundum type and type I glycogen storage disease

A rare combination of atrial septal defect of the secundum type and type I glycogen storage disease was seen with early fatal outcome due to rapidly progressive severe pulmonary vascular disease. Possible reasons for the unexpected, rapidly progressive pulmonary vascular disease are discussed.     

Severe pulmonary arterial hypertension in type 1 glycogen storage disease

Pulmonary arterial hypertension is characterised by the presence of pulmonary hypertension (mean pulmonary artery pressure > 25 mmHg at rest or >30 mmHg during exercise) and normal pulmonary wedge pressure (<12 mmHg). Several risk factors for pulmonary arterial hypertension have been described. In the absence of any factor or condition suspected to play a causal or facilitating role in the process, pulmonary hypertension is “unexplained” (primary pulmonary hypertension, PPH). PPH is a rare condition, with an estimated incidence of 2 per million people. Recent genetic studies have identified mutations in the bone morphogenetic protein receptor-II (BMPR-II) gene, a receptor member of the transforming growth factor-beta family, in a majority of familial cases of PPH. Interestingly, 25% of patients displaying sporadic PPH may also have mutations in theBMPR-II gene, emphasising the relevance of genetic susceptibility for this severe condition. Other molecular and biochemical processes behind the complex vascular changes associated with pulmonary arterial hypertension are currently investigated. Type 1a glycogen storage disease caused by a deficiency of glucose-6-phosphatase has an estimated incidence of 1 per 100,000 with a few reported cases of unexplained severe pulmonary hypertension. The occurrence of pulmonary arterial hypertension in type 1a glycogen storage disease could be due to vasoconstrictive amines such as serotonin, a pulmonary vasoconstrictor and growth factor for vascular smooth muscle cells stored in platelets. Published online: 31 July 2002     

Effective renal plasma flow in patients with glycogen storage disease type I

To evaluate effective renal plasma flow (ERPF) we performed renal scintigraphies with^99mTc-Mercaptoacetyl-triglycine (MAG₃) in ninepatients with glycogen storage disease I (GSD I) (age: 16±7 years). Two patients presented with proteinuria, none showed hyperaminoaciduria, disturbed tubular reabsorption of phosphate or hypertension.^99mTc-MAG₃ clearance values were elevated in eight out of nine patients (865±233 ml/min/1.73 m² body surface area) and exceeded the agedependent mean values by 21%–145%. ERPF values in patients with poor metabolic control were higher than in patients with long-term good metabolic control (988±186 vs. 619±55 ml/min/1.73 m²;P<0.05). We conclude that enhanced ERPF is a common finding in GSD I patients, which preceeds clinically overt nephropathy. Renal scientigraphy with^99mTc MAG₃ is a suitable method for the early detection and monitoring of kidney dysfunction in GSD I.     

Biochemical diagnosis of Type 1b glycogen storage disease

A child with the classical signs and symptoms of Type 1 glycogen storage disease is presented who on investigation was shown to have a recently described variant of this disease known as Type 1b glycogen storage disease. A reliable and simple procedure for the diagnosis and differentiation of Types 1 and 1b glycogen storage disease is described, as the conventional diagnostic approach of assaying glucose-6-phosphate phosphohydrolase in frozen tissue will not diagnose Type 1b glycogen storage disease.
A portion of biopsy tissue should be maintained at a temperature near 0°C (but not frozen) and the remainder frozen. Glucose-6-phosphate phosphohydrolase assays are carried out on the tissue homogenates of both portions. In Type 1 glycogen storage disease, glucose-6-phosphate phosphohydrolase activity will be tow or absent in both frozen and unfrozen tissues. In Type 1b glycogen storage disease the frozen tissue homogenate will exhibit normal glucose-6-phosphate phosphohydrolase activity due to the disruption of the microsomes by tee crystals, white in the unfrozen tissue low levels of glucose-6-phosphate phosphohydrolase activity will be detected.     

Focal nodular hyperplasia in an adolescent with glycogen storage disease type I with mesocaval shunt operation in childhood: a case report and review of the literature

As patients with glycogen storage disease type I survive longer, cases with hepatic tumor have been increasingly documented. A 16 year old boy with glycogen storage disease type I was evaluated for multiple liver tumors. He was diagnosed on clinical features at 9 months of age and underwent a mesocaval shunt operation at 5 years of age. The biopsy of one of the masses showed focal nodular hyperplasia. This is uncommon in patients with glycogen storage disease type I, compared to those with adenoma or malignant hepatic tumor. The association of a portacaval shunt with focal nodular hyperplasia is significant compared to other tumors. An environment of high estrogen concentration or sex hormone binding globulin accompanied by shunt operation may cause focal nodular hyperplasia to develop in the liver of patients with glycogen storage disease type I.     

Effects of cornstarch treatment in very young children with type I glycogen storage disease

Three children aged 1–2 years with glycogenosis type I were treated with 2 g/kg bodyweight oral cornstarch per meal (4–5 times a day) for a period up to 16 months. In comparison to the previous dietary regimen (day and nocturnal feedings every 3 h) the cornstarch diet stabilised serum glucose profiles and dramatically improved secondary hyperlipoproteinaemia. Mean total triglycerides decreased up to one half, consistent with a fall of very low density lipoprotein-triglycerides up to two thirds. Metabolic acidosis and hyperuricaemia did not occur and normal growth rates (0.7–1 cm/month) were achieved. We conclude that the cornstarch regimen even in the age group up to 2 years can be considered as an efficient alternative in the treatment of glycogenosis type I patients with less frequent feedings and without nocturnal infusion.     

Type la glycogen storage disease with focal nodular hyperplasia in siblings

Glycogen storage disease type I (GSD-I) is an inherited disorder that is due to a glucose-6-phosphatase (G6Pase) deficiency. There have been recent reports of hepatocellular tumors in adults with this disease. Hepatic adenoma is the most common tumor described but others, including hepatocellular carcinomas, hepatoblastomas, and focal nodular hyperplasia (FNH) have been reported. FNH of the liver is a rare benign lesion that has been reported in eight patients with GSD-I. Three of these eight patients, in addition to the patient in our study, had been treated with portacaval shunts. When these patients were compared with patients who had not received such treatment, it appeared that the portacaval shunts may have induced the development of FNH and may have been associated with earlier complications. FNH is a benign tumor that may coexist with adjacent fibrolamillar carcinomas and/or adenomas and requires careful follow-up.     

Brain damage in glycogen storage disease type I

OBJECTIVE: To investigate brain morphology and function in patients with glycogen storage disease type I (GSDI). STUDY DESIGN: Nineteen patients (13 females and 6 males, aged 0.9-22.6 years) and 38 sex- and age-matched controls entered the study. Neurological examinations, psychometric tests (IQ, tests of performance and verbal abilities), standard electroencephalogram (EEG), somatosensory (SEPs), visual (VEPs), and brain-stem auditory evoked potentials (BAEPs), and brain magnetic resonance imaging (MRI) were performed. RESULTS: The results of tests of performance ability were lower in patients than in controls (P <.05). The prevalence of abnormal EEG findings (26.3% versus 2.6%), VEPs (38.4% versus 7.7%), SEPs (23.0% versus 0%), and BAEPs abnormalities (15.7% versus 0%) was higher in patients than in controls (P <.05). MRI pattern was altered in 57.1% of patients and was normal in all controls (P <.05). Both results of tests of performance ability and BAEPs abnormalities significantly correlated with the frequency of admissions for hypoglycemia, whereas EEG abnormalities correlated with dietary compliance (P <.05). CONCLUSIONS: Brain damage, probably caused by recurrent severe hypoglycemia, may be present in patients with GSDI.     

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

To evaluate the effects of uncooked cornstarch (UCS) on metabolic control, growth, and complications of pubertal and postpubertal, subjects with type 1 a 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 μg/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 CO₂ 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. Published online: 31 July 2002     

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??Abstract?? Objective To summarize the clinical features of hepatic glycogen storage disease to improve the diagnosis and treatment and decrease the possibility of misdiagnosis. Methods Twelve cases of hepatic glycogen storage disease in Shengjing Hospital from May, 2007 to November, 2013 were analyzed retrospectively and followed up. Results Two cases were misdiagnosed in the 5 final diagnosed cases at first treatment. Liver dysfunction and growth retardation are the main symptoms, 2 cases with low blood glucose and 3 cases with jaundice??4 cases were screened positive result for epinephrine stimulating test. Two time of follow-up confirmed these cases still suffered from hepatomegaly and splenomegaly, liver dysfunction, growth retardation, etc. In suspected diagnosed group,only 1 case was screened positive result for epinephrine stimulating test. Conclusion The clinical manifestations of hepatic glycogen storage disease are multiple. Therefore, physicians should have sufficient recognition for this disease and give a right and prompt diagnosis based on family history, physical examinations and laboratory findings.     

Cardiac involvement in glycogen storage disease type III

Twenty patients with enzymatically proven glycogen storage disease type III (GSD III) aged 3–30 years underwent cardiological evaluation. Seventeen showed subclinical evidence of cardiac involvement in form of ventricular hypertrophy on ECG. Of 16 patients in whom an ECG examination was performed, 13 had abnormal echocardiographic features. Only 2 patients had cardiomegaly on X-ray. The cardiac findings in 1 of the patients, a 25-year-old female with clinically evident cardiomyopathy are described in detail. In view of our findings, patients with established GSD III, should not only be investigated regarding their muscular involvement, but should also undergo a detailed evaluation of their cardiac status.Abbreviation GSD glycogen storage disease     

Secondary amyloidosis in glycogen storage disease type Ib

We observed the development of generalized amyloidosis in a girl with glycogen storage disease type Ib (GSD-Ib) who showed neutropenia, neutrophil dysfunction and recurrent infections. Renal and thyroid biopsies showed secondary amyloidosis, characterized by the presence of potassium permanganate sensitive Dylon positive deposits in glomeruli, renal vessels and thyroid interstitium. Immunohistochemistry showed that the deposits were composed of amyloid A (AA) protein. Possibly neutrophil abnormalities are involved in the pathogenesis of amyloidosis.     

Effect of clonidine on the height of a child with glycogen storage disease type VI: A 13 year follow-up study

A 9-month-old male was found to have hepatomegaly when he was treated by his doctor for bronchitis. At the age of 2 years and 3 months, glycogen storage disease (GSD) of type VI (GSD VI) was diagnosed in this patient. Despite the recommended diet therapy, his growth was not good, changing under or along the line of ?2.0 SD. At the age of 6 years, oral clonidine therapy (0.15 mg/day, 0.2 mg/m² body surface per day) was started. Six to 10 months after the initiation of clonidine therapy, his height began to increase more than the values for ?2.0 SD and once reached the value for ?1.0 SD at the age of 10 years. His growth rate and bone age increased. Clonidine therapy was continued regularly for 7 years until the age of 13 years, 11 months. At that time his development was normal and his height reached 150.8 cm (–1.34 SD). However, cessation of the treatment at the patient's free will resulted in a reduction of the growth rate at age 15 years 6 months. These observations suggest the effect of clonidine therapy on height. Side effects were not noted during the clonidine therapy. Other clinical and laboratory findings of GSD VI also completely improved during treatment. In conclusion, administration of clonidine could be another treatment modality in children with GSD, not only of type VI but also I and III.     

Bone mineralisation in type 1 glycogen storage disease

Radial bone mineral content (BMC) was measured using single photon absorptiometry in 11 prepubertal children, aged 3.4–12.6 years, with glycogen storage disease type 1 (GSD-1), 2 of whom were receiving granulocyte colony stimulating factor (G-CSF) therapy for chronic neutropenia. Patients were short (median height SD score –1.35, range –3.74 to –0.27), and had reduced BMC Z scores (median 1.79, range –6.35 to +0.27) and radial bone width Z scores (median –0.72, range –2.00 to +0.68). Those receiving G-CSF did not differ significantly from the rest of the group. Generally dietary calcium intake was low and urinary calcium excretion increased. Urinary lactate excretion was high but did not correlate with BMC Z scores. Factors regulating bone metabolism (parathyroid hormone and 25-hydroxy vitamin D concentrations) and markers of bone formation (osteocalcin and skeletal alkaline phosphatase) were not increased implying that there was no compensation for increased bone resorption.Conclusion Patients with GSD-1 may be at increased risk of fracture in later life and require close attention to metabolic control and calcium balance.