Living donor liver transplantation for glycogen storage disease type Ib

Kasahara, Mureo; Horikawa, Reiko; Sakamoto, Seisuke; Shigeta, Takanobu; Tanaka, Hideaki; Fukuda, Akira; Abe, Kodai; Yoshii, Keisuke; Naiki, Yasuhiro; Kosaki, Rika; Nakagawa, Atsuko

doi:10.1002/lt.21929

Cited by 34 publications

(28 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…107 on the other hand, in children with GSD-I, living-donor or reduced-size liver transplantation 108,109 has corrected metabolic abnormalities in all nine cases of GSD-Ia and four cases of GSD-Ib documented and improved neutropenia and decreased infectious episodes in children with GSD-Ib. 109 In a 21-year-old patient with GSD-I and multiple hepato-cellular adenomas, reduced-size liver transplantation was also successful, 110 which suggests that living-donor liver transplantation is a viable option to restore normal metabolic balance in some patients with GSD-I. Despite the transplant guidelines, the liver transplant priority for patients with GSD-I, calculated on the basis of a score for end-stage liver disease, is extremely low.…”

Section: Treatmentmentioning

confidence: 99%

Glycogen storage disease type I and G6Pase-β deficiency: etiology and therapy

2010

View full text Add to dashboard Cite

Glycogen storage disease type I (GSD-I) consists of two subtypes: GSD-Ia, a deficiency in glucose-6- phosphatase-α (G6Pase-α) and GSD-Ib, which is characterized by an absence of a glucose-6-phosphate (G6P) transporter (G6PT). A third disorder, G6Pase-β deficiency, shares similarities with this group of diseases. G6Pase-α and G6Pase-β are G6P hydrolases in the membrane of the endoplasmic reticulum, which depend on G6PT to transport G6P from the cytoplasm into the lumen. A functional complex of G6PT and G6Pase-α maintains interprandial glucose homeostasis, whereas G6PT and G6Pase-β act in conjunction to maintain neutrophil function and homeostasis. Patients with GSD-Ia and those with GSD-Ib exhibit a common metabolic phenotype of disturbed glucose homeostasis that is not evident in patients with G6Pase-β deficiency. Patients with a deficiency in G6PT and those lacking G6Pase-β display a common myeloid phenotype that is not shared by patients with GSD-Ia. Previous studies have shown that neutrophils express the complex of G6PT and G6Pase-β to produce endogenous glucose. Inactivation of either G6PT or G6Pase-β increases neutrophil apoptosis, which underlies, at least in part, neutrophil loss (neutropenia) and dysfunction in GSD-Ib and G6Pase-β deficiency. Dietary and/or granulocyte colony-stimulating factor therapies are available; however, many aspects of the diseases are still poorly understood. This Review will address the etiology of GSD-Ia, GSD-Ib and G6Pase-β deficiency and highlight advances in diagnosis and new treatment approaches, including gene therapy.

show abstract

Section: Treatmentmentioning

confidence: 99%

Glycogen storage disease type I and G6Pase-β deficiency: etiology and therapy

2010

View full text Add to dashboard Cite

show abstract

“…Liver grafting corrects the hypoglycemia and the other biochemical anomalies but the correction of neutropenia is not constant [106,107]. It has not been proven that it can prevent renal involvement, which may even be worsened by the immunosuppressive therapy.…”

Section: Management Including Treatment [1263094]mentioning

confidence: 99%

Glucose-6-phosphatase deficiency

Froissart

Piraud

Boudjemline

et al. 2011

Orphanet J Rare Dis

189

159

View full text Add to dashboard Cite

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 hepatoc...

show abstract

“…1h). In addition, living donor partial liver transplantation has been performed in patients with GSD-1b resulting in restored glucose homeostasis and an increase, but no complete restoration, of the number of neutrophils (Adachi et al 2004;Kasahara et al 2009). Since chimerism has been observed in the leukocyte population (Adachi et al 2004), it cannot be excluded that the observed increase in neutrophil numbers is due to accidental transplantation and subsequent migration of healthy donor derived HSCs to the recipient's bone marrow.…”

Section: Discussionmentioning

confidence: 98%

Survival, but not maturation, is affected in neutrophil progenitors from GSD‐1b patients

Visser

Jager

Verhagen

et al. 2011

J of Inher Metab Disea

View full text Add to dashboard Cite

Glycogen storage disease type 1b (GSD 1b) is caused by mutations in the Glucose-6-phosphate transporter and is characterized by impaired glucose homeostasis. In addition, GSD-1b is associated with chronic neutropenia resulting in recurrent infections and inflammatory bowel disease. It is unclear whether the neutropenia is solely due to enhanced apoptosis of mature neutrophils or whether aberrant neutrophil development may also contribute. Here we demonstrate that hematopoietic progenitors from GSD-1b patients are not impaired in their capacity to develop into mature neutrophils. However, optimal survival of neutrophil progenitors from GSD-1b patients requires high glucose levels (> 200 mg dl(-1)), suggesting that even under normoglycemic conditions these cells are more prone to apoptosis. Furthermore, analysis of cytokine levels in peripheral blood suggests an inflammatory state with an inverse correlation between the level of inflammation and the number of neutrophils. Finally, in some patients, with low numbers of peripheral blood neutrophils, high numbers of neutrophils were observed in the intestine. Together, these results suggest that the neutropenia observed in GSD-1b patients is not caused by impaired maturation, but may be caused by both increased levels of apoptosis and egress of neutrophils from the blood to the inflamed tissues.

show abstract

Living donor liver transplantation for glycogen storage disease type Ib

Cited by 34 publications

References 23 publications

Glycogen storage disease type I and G6Pase-β deficiency: etiology and therapy

Glycogen storage disease type I and G6Pase-β deficiency: etiology and therapy

Glucose-6-phosphatase deficiency

Survival, but not maturation, is affected in neutrophil progenitors from GSD‐1b patients

Contact Info

Product

Resources

About