Neutropenia in glycogen storage disease Ib: outcomes for patients treated with granulocyte colony-stimulating factor.
(Clinical Trial;Journal Article;Multicenter Study)
PURPOSE OF REVIEW: Glycogen storage disease Ib (GSD Ib) is characterized by hepatomegaly, hypoglycemia, neutropenia, enterocolitis and recurrent bacterial infections. It is attributable to mutations in G6PT1, the gene for the glucose-6-phosphate transporter responsible for transport of glucose into the endoplasmic reticulum. Neutropenia in GSD Ib is now frequently treated with granulocyte colony-stimulating factor (G-CSF). We formed a cooperative group to review outcomes of the long-term treatment of GSD Ib patients treated with G-CSF. RECENT FINDINGS: The study enrolled 103 patients (48 men and 55 women), including 47 currently adult patients. All of these patients were treated with G-CSF, starting at a median age of 3.8 years (range 0.04-33.9 years) with a median dose of 3.0 mcg/kg/day (range 0.01-93.1 mcg/kg/day) for a median of 10.3 years (range 0.01-29.3 years). Neutrophils increased in response to G-CSF in all patients (median values before G-CSF 0.2 × 10/l, on G-CSF 1.20 x 10/l). Treatment increased spleen size (before G-CSF, 47%, on treatment on G-CSF 76%), and splenomegaly was the dose-limiting adverse effect of treatment (pain and early satiety). Clinical observations and records attest to reduce frequency of infectious events and the severity of inflammatory bowel symptoms, but fever and recurrent infections remain a significant problem. In the cohort of patients followed carefully through the Severe Chronic Neutropenia International Registry, four patients have developed myelodysplasia or acute myeloid leukemia and we are aware of four other cases, (altogether seven on G-CSF, one never treated with G-CSF). Liver transplantation in five patients did not correct neutropenia. Four patients had hematopoietic stem cell transplantation; two adults and two children were transplanted; one adult and one child survived. SUMMARY: GSD Ib is a complex disorder of glucose metabolism causing severe chronic neutropenia. G-CSF is effective to raise blood neutrophil counts and reduce fevers and infections in most patients. In conjunction with other therapies (salicylates, mesalamine sulfasalazine and prednisone), G-CSF ameliorates inflammatory bowel symptoms, but doses must be limited because it increases spleen size associated with abdominal pain.
Dale, DC; Bolyard, AA; Marrero, T; Kelley, ML; Makaryan, V; Tran, E; Leung, J; Boxer, LA; Kishnani, PS; Austin, S; Wanner, C; Ferrecchia, IA; Khalaf, D; Maze, D; Kurtzberg, J; Zeidler, C; Welte, K; Weinstein, DA
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