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We studied the genotype/phenotype correlation in a cohort of glycogen storage disease type (GSD) 1b patients. A total of 25 GSD1b patients, 13 females and 12 males, age range: 4.3-28.4 years, mean:14.6±6.8 years; median: 15 years, repre senting the entire case load of Italian GSD1b patients, were enrolled in the stu dy. Molecular analysis of the glucose 6-phosphate translocase (G6PT1) gene was performed in all patients. We analysed the presence of a correlation among both the clinical features associated with GSD1b (neutropenia, frequency of admission to the hospital for severe infections) and the presence of systemic complicatio ns (liver adenomas, nephropathy, bone mineral density defect, polycystic ovaries , short stature, in-flammatory bowel disease) and the mutations detected in each pati ent. Nine patients were homozygous or compound heterozygous for mutations causin g stop codons. In particular, three patients were homozygous for the same mutati on (400X); of these patients, one showed chronic neutropenia with severe and fre quent infections and severe inflammatory bowel disease, another patient cyclic n eutropenia associated with rare bacterial infections and mild bowel involvement and the last one normal neutrophil count. Two patients were homozygous for the m utation 128X; one of these patients did not show neutropenia, whereas the other one had severe neutropenia needing frequent hospital admission and was under gra nulocyte-colony stimulating factor treatment. In three patients no mutations we re detected. Conclusion:no correlation was found between individual mutations an d the presence of neutropenia, bacterial infections and systemic complications. These results suggest that different genes and proteins modulate neutrophil diff erentiation, maturation and apoptosis and thus the severity and frequency of inf ections. The absence of detectable mutations in three patients could suggest tha t a second protein plays a role in microsomal phosphate transport.
We studied the genotype / phenotype correlation in a cohort of glycogen storage disease type (GSD) 1b patients. A total of 25 GSD1b patients, 13 females and 12 males, age range: 4.3-28.4 years, mean: 14.6 ± 6.8 years; median : 15 years, repre senting the entire case load of Italian GSD1b patients, were enrolled in the stu dy. Molecular analysis of the glucose 6-phosphate translocase (G6PT1) gene was performed in all patients. the clinical features associated with GSD1b (neutropenia, frequency of admission to the hospital for severe infections) and the presence of systemic complications in liver (liver adenomas, nephropathy, bone mineral density defect, polycystic ovaries, short stature, in-flammatory bowel disease) and the mutations detected in each pati ent. Nine patients were homozygous or compound heterozygous for mutations causin g stop codons. In particular, three patients were homozygous for the same mutati on (400X); of these patients, on e showed chronic neutropenia with severe and fre quent infections and severe inflammatory bowel disease, another patient cyclic n eutropenia associated with rare bacterial infections and mild bowel involvement and the last one normal neutrophil count. Two patients were homozygous for the utation 128X; one of these patients did not show neutropenia, while the other one had severe neutropenia needing frequent hospital admission and was under gra nulocyte-colony stimulating factor treatment. No correlation was found between individual mutations an d the presence of neutropenia, bacterial infections and systemic complications. These results suggest that different genes and proteins modulate neutrophil diff erentiation, maturation and apoptosis and thus the severity and frequency of inf ections. The absence of detectable mutations in three patients could suggest tha ta second protein plays a role in microsomal phosphate transpor t.