Urinary Levels of Glc4 Abnormally High in Pompe Patients, Turkish Study Finds

Urinary levels of a proposed Pompe disease biomarker known as Glc4 are higher in patients with either infantile-onset or late-onset forms of this disorder compared to healthy individuals in the Turkish population, a study shows.

As Glc4 (or glucose tetrasaccharide) levels vary with age, identifying appropriate reference ranges for individuals of different ages is essential when using this marker to test for Pompe disease, scientists said.

The study, “The decision-making levels of urine tetrasaccharide for the diagnosis of Pompe disease in the Turkish population,” was published in the Journal of Pediatric Endocrinology and Metabolism.

Pompe disease is characterized by the abnormal buildup of a sugar called glycogen resulting from no functional acid alpha-glucosidase (GAA), an enzyme involved in breaking down glycogen. The gold standard for diagnosing Pompe disease is measuring the activity of GAA in skin cells. However, the technique used is expensive and invasive, and requires specialized equipment. As such, there is an ongoing search for new markers that could be used to diagnose this disorder in a more convenient manner.

Researchers have suggested that high levels of a sugar molecule called Glc4 in urine could be indicative of Pompe disease, as this sugar is biochemically related to glycogen. For Glc4 to be a useful biomarker, understanding normal (healthy) levels is necessary, as well as how Glc4 levels normally vary in different groups, most notably individuals of different ages.

In the new study, researchers in Turkey measured Glc4 levels in the urine of 220 healthy subjects, ranging in age from infants to 60-year-olds.

The scientists observed that urine Glc4 levels declined significantly with increasing age, with the highest levels seen in the first years of life.

Based on these findings, the researchers defined normal Glc4 ranges for four age groups. For infants up to 1 year, the range was 0.08–11.30 millimoles per mol (mmol/mol) of creatinine (a product of muscle metabolism and eating meat, which is excreted in urine). For those from 13 months to 2 years, the normal range was 0.30–9.60 mmol/mol of creatinine. For children from 25 months to 6 years, the range was 0.07–8.93 mmol/mol of creatinine, while for those older than 6, the reference values were 0.12–3.65 mmol/mol of creatinine.

Glc4 levels were also measured in four infants with infantile-onset Pompe disease (all younger than 1) and in five people with late-onset Pompe disease (age range 13–34 years). The mean urine Glc4 levels were 99.8 mmol/mol of creatinine in the infantile-onset group and 12.1 mmol/mol of creatinine in late-onset patients — significantly higher than the upper end of the respective normal range.

“In conclusion,” the researchers wrote, “we presented reference intervals with respect to the age of healthy subjects in the Turkish population and highlighted the differences in urine Glc4 levels of early-onset and late-onset Pompe patients.”

“As the reference intervals of Glc4 in urine changed with age, definition of the decision levels by age is critically important especially for diagnosing the late-onset Pompe patients with mild symptoms,” they added.