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, representing the entire case load of Italian GSD1b patients, were enrolled in the study. 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 complications (liver
adenomas, nephropathy, bone mineral density defect, polycystic ovaries, short stature,
inflammatory bowel disease) and the mutations detected in each patient. Nine patients were homozygous or compound heterozygous for mutations causing
stop codons. In particular, three patients were homozygous for the same mutation (400X); of these patients, one showed chronic
neutropenia with severe and frequent
infections and severe
inflammatory bowel disease, another patient
cyclic neutropenia associated with rare
bacterial infections and mild bowel involvement and the last one normal neutrophil count. Two patients were homozygous for the mutation 128X; one of these patients did not show
neutropenia, whereas the other one had severe
neutropenia needing frequent hospital admission and was under
granulocyte-colony stimulating factor treatment. In three patients no mutations were detected.
CONCLUSION: No correlation was found between individual mutations and the presence of
neutropenia,
bacterial infections and systemic complications. These results suggest that different genes and
proteins modulate neutrophil differentiation, maturation and apoptosis and thus the severity and frequency of
infections. The absence of detectable mutations in three patients could suggest that a second
protein plays a role in microsomal
phosphate transport.