SNP Shot: Genomic Insights

Glycogen storage disease type I (GSDI), also known as von Gierke disease, is a genetic condition where the body accumulates glycogen, a complex sugar, within cells. This buildup particularly affects the liver, kidneys, and small intestines, hindering their normal function.

Symptoms usually appear around 3 to 4 months of age, when infants begin sleeping through the night and feeding less frequently. Affected babies may experience low blood sugar (hypoglycemia), potentially leading to seizures. Other signs include lactic acid buildup (lactic acidosis), elevated uric acid levels (hyperuricemia), and high levels of fats in the blood (hyperlipidemia). As children with GSDI grow, they often have thin limbs, short stature, and an enlarged liver that causes the abdomen to protrude. The kidneys may also enlarge. Some individuals develop diarrhea and cholesterol deposits in the skin (xanthomas).

Individuals with GSDI may experience delayed puberty. Later in life, during young to mid-adulthood, they may develop osteoporosis (thinning bones), gout (arthritis caused by uric acid crystals), kidney disease, and pulmonary hypertension (high blood pressure in the lung arteries). Females may also experience abnormal ovary development (polycystic ovaries). Liver adenomas, usually non-cancerous tumors, can form in teens and adults with GSDI. While generally benign, these tumors can sometimes become cancerous.

GSDI is classified into two main types, GSDIa and GSDIb, based on varying symptoms and genetic causes. Formerly, types Ic and Id were described, but these are now considered variations of GSDIb, which is sometimes referred to as GSD type I non-a.

A significant characteristic of GSDIb is neutropenia, a shortage of white blood cells, increasing susceptibility to recurrent bacterial infections, often apparent by age 1. Many individuals with GSDIb also suffer from inflammatory bowel disease. Oral health issues are common in GSDIb, including cavities, gingivitis (gum inflammation), chronic periodontal disease, abnormal tooth development, and mouth ulcers. These neutropenia and oral problems are specific to GSDIb and are not typically observed in GSDIa.

Inheritance:

GSDI follows an autosomal recessive inheritance pattern. This means that both parents, while carrying one copy of the mutated gene, usually do not exhibit symptoms of the condition. The child inherits a mutated copy from each parent.