Metabolic Control, Quality of Life, and Body Image in Patients with Glycogen Storage Disease Type Ia

Glycogen storage disease is a group of inborn errors of metabolism, with type Ia being the most common form of the disorder. Glycogen storage disease type Ia (GSDIa) is a multisystemic condition in which individuals have various complications secondary to an inability to properly break down glycogen and to perform gluconeogenesis. Complex management is then necessary for patients and includes dietary modification, frequent cornstarch usage, and evaluation for additional complications such as hepatic adenomas, hypertriglyceridemia, and kidney disease. Previous studies have found lower scores in quality of life and body image in GSDIa patients; however, the specific factors influencing this relationship remain unknown. In this study, 24 adult participants (n=24) with glycogen storage disease type Ia completed a survey including measures of health-related quality of life, body image, and metabolic control. Results found that quality of life was significantly lower than the general population on both the physical and mental component scores (t=-3.11, p=0.005; t=-2.21, p=0.03). Additionally, body image was significantly lower on all subscales: Weight (t=-5.88,

LIVER TRANSPLANTATION FOR TYPE I GLYCOGEN STORAGE DISEASE

A 16½-year-old girl with type I glycogen storage disease was treated by orthotopic liver transplantation under cyclosporin/steroid immunosuppression. All metabolic stigmata of the disease were relieved and 1 year postoperatively she follows a normal diet and lifestyle

Liver transplantation for type IV glycogen storage disease

TYPE IV glycogen storage disease is a rare autosomal recessive disorder (also called Andersen's disease1 or amylopectinosis) in which the activity of branching enzyme alpha-1, 4-glucan: alpha-1, 4-glucan 6-glucosyltransferase is deficient in the liver as well as in cultured skin fibroblasts and other tissues.2,3 This branching enzyme is responsible for creating branch points in the normal glycogen molecule. In the relative or absolute absence of this enzyme, an insoluble and irritating form of glycogen, an amylopectin-like polysaccharide that resembles plant starch, accumulates in the cells. The amylopectin-like form is less soluble than normal glycogen, with longer outer and inner chains. © 1991, Massachusetts Medical Society. All rights reserved

Portacaval shunt for glycogen storage disease and hyperlipidaemia.

Complete portacaval shunt was used to treat 10 patients with glycogen storage disease. A favourable effect was noted on body growth and a number of metabolic abnormalities. More recently, continous night feedings with an intermittently placed gastric tube or through a gastrostomy has been shown to be helpful either before or after portacaval shunts. Such alimentation techniques may eliminate the need for shunts in some patients and be of adjuvant benefit in others. Portacaval shunt was also used for three children who had homozygous Type II hyperlipidaemia. Substantial reductions in serum cholesterol concentration were observed, as well as resorption of xanthomas. Reversal of some cardiovascular lesions has been documented. The benefits of portacaval shunt in these disorders is probably due to the change in the hormone climate of the liver and the whole organism brought about by diversion of the hormone-rich splanchnic venous blood around the liver

Chimerism after Liver Transplantation for Type IV Glycogen Storage Disease and Type 1 Gaucher's Disease

Background: Liver transplantation for type IV glycogen storage disease (branching-enzyme deficiency) results in the resorption of extrahepatic deposits of amylopectin, but the mechanism of resorption is not known. Methods: We studied two patients with type IV glycogen storage disease 37 and 91 months after liver transplantation and a third patient with lysosomal glucocerebrosidase deficiency (type 1 Gaucher's disease), in whom tissue glucocerebroside deposition had decreased 26 months after liver replacement, to determine whether the migration of cells from the allograft (microchimerism) could explain the improved metabolism of enzyme-deficient tissues in the recipient. Samples of blood and biopsy specimens of the skin, lymph nodes, heart, bone marrow, or intestine were examined immunocytochemically with the use of donor-specific monoclonal anti-HLA antibodies and the polymerase chain reaction, with preliminary amplification specific to donor alleles of the gene for the beta chain of HLA-DR molecules, followed by hybridization with allele-specific oligonucleotide probes. Results: Histopathological examination revealed that the cardiac deposits of amylopectin in the patients with glycogen storage disease and the lymph-node deposits of glucocerebroside in the patient with Gaucher's disease were dramatically reduced after transplantation. Immunocytochemical analysis showed cells containing the HLA phenotypes of the donor in the heart and skin of the patients with glycogen storage disease and in the lymph nodes, but not the skin, of the patient with Gaucher's disease. Polymerase-chain-reaction analysis demonstrated donor HLA-DR DNA in the heart of both patients with glycogen storage disease, in the skin of one of them, and in the skin, intestine, blood, and bone marrow of the patient with Gaucher's disease. Conclusions: Systemic microchimerism occurs after liver allotransplantation and can ameliorate pancellular enzyme deficiencies., In patients with type IV glycogen storage disease, deficiency of the branching enzyme α-1,4-glucan:α-1,4-glucan 6-glucosyltransferase is responsible for the accumulation in the liver and elsewhere of an insoluble and irritating amylopectin-like polysaccharide1. We recently described the absorption of this amylopectin from the extrahepatic tissues after liver transplantation,2 leading Howell to predict that an explanation of the benefit would “clearly teach us a great deal about transplantation”3. That prediction has been shown to be accurate by our observation in this study that patients with type IV glycogen storage disease in whom liver transplantation was successful became chimeras: the cells… © 1993, Massachusetts Medical Society. All rights reserved

SLC37A4-CDG : mislocalization of the glucose-6-phosphate transporter to the Golgi causes a new congenital disorder of glycosylation

Loss-of-function of the glucose-6-phosphate transporter is caused by biallelic mutations in SLC37A4 and leads to glycogen storage disease Ib. Here we describe a second disease caused by a single dominant mutation in the same gene. The mutation abolishes the ER retention signal of the transporter and generates a weak Golgi retention signal. Intracellular mislocalization of the transporter leads to a congenital disorder of glycosylation instead of glycogen storage disease

Pituitary hypoplasia and growth hormone deficiency in a woman with glycogen storage disease type Ia: a case report

<p>Abstract</p> <p>Introduction</p> <p>Growth retardation is one of the cardinal manifestations of glycogen storage disease type Ia. It is unclear which component of the growth hormone and/or insulin-like growth factor axis is primarily disrupted, and management of growth impairment in these patients remains controversial. Here we report the first case in the literature where glycogen storage disease type Ia is associated with pituitary hypoplasia and growth hormone deficiency.</p> <p>Case presentation</p> <p>A 20-year-old woman with glycogen storage disease type Ia was admitted to our endocrinology department because of growth retardation. Basal and overnight growth hormone sampling at 2-hour intervals demonstrated low levels; however, provocative testing revealed a relatively normal growth hormone response. A hypoplastic anterior pituitary with preserved growth hormone response to provocative testing suggested the possibility of growth hormone neurosecretory dysfunction and/or primary pituitary involvement.</p> <p>Conclusion</p> <p>Pituitary hypoplasia may result from growth hormone-releasing hormone deficiency, a condition generally known as growth hormone neurosecretory dysfunction. It is an abnormality with a spontaneous and pulsatile secretion pattern, characterized by short stature, growth retardation and normal serum growth hormone response to provocative testing. However, in the case described in this report, a normal although relatively low growth hormone response during insulin tolerance testing and pituitary hypoplasia suggested that primary pituitary involvement or growth hormone neurosecretory dysfunction may occur in glycogen storage disease type Ia. This is a potential cause of growth failure associated with a lower somatotroph mass, and may explain the variable responsiveness to growth hormone replacement therapy in people with glycogen storage disease.</p

Portal diversion in glycogen storage disease

Two children with glycogen storage disease were treated with portacaval transposition. The first is alive and in good health more than 5 years later. She underwent a rapid increase in growth after the operation, while the liver remained the same size. The second patient died within 2 days after the transposition, apparently because the portal system of the swollen liver was unable to transmit the vena caval inflow. © 1969

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. Postoperative 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 T 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