Original Articles
Decreased urinary citrate excretion in type 1a glycogen storage disease*,**

https://doi.org/10.1067/mpd.2001.111322Get rights and content

Abstract

Objectives: To quantify urinary citrate and calcium excretion and systemic acid-base status in patients with type 1a glycogen storage disease (GSD1a) and to investigate their relationship to renal complications. Study design: Fifteen patients (7 male and 8 female; age range, 3–28 years) were studied during annual evaluations of metabolic control. All were treated with intermittent doses of uncooked cornstarch. Hourly blood sampling and a 24-hour urine collection were obtained while subjects followed their usual home dietary regimen. Results: All but the youngest subject had low levels of citrate excretion (mean 2.4 ± 1.8 mg/kg/d; 129 ± 21 mg citrate/g creatinine). Normally, urinary citrate excretion increases with age; however, in patients with GSD1a, a strong inverse exponential relationship was found between age and citrate excretion (r = –0.84, P <0001). Urinary citrate excretion was unrelated to markers of metabolic control. Hypercalciuria occurred in 9 of 15 patients (mean urinary calcium/creatinine ratio, 0.27 ± 0.15) and was also inversely correlated with age (r = –0.62, P =001). Conclusions: Hypocitraturia that worsens with age occurs in metabolically compensated patients with GSD1a. The combination of low citrate excretion and hypercalciuria appears to be important in the pathogenesis of nephrocalcinosis and nephrolithiasis. Citrate supplementation may be beneficial in preventing or ameliorating nephrocalcinosis and the development of urinary calculi in GSD1a. (J Pediatr 2001;138:378-82)

Section snippets

Subjects

We studied 15 patients (7 males and 8 females) between the ages of 3 and 28 years (mean age, 17.4 ± 4.6 years) as part of routine annual evaluations of their clinical status, physical development, and metabolic control. The diagnosis of GSD1a was confirmed by liver biopsy and documentation of deficient hepatic glucose-6-phosphatase activity. Subjects all received continuous glucose therapy from the time of diagnosis (mean age, 0.5 ± 0.4 years). Of the 15 subjects, 11 were initially treated with

Results

Twenty-four separate 24-hour urine collections were obtained from the 15 subjects. Five subjects had citrate excretion determined on successive admissions with a minimum of 1 year between sample collections. Compared with the normal standards of urinary citrate excretion, 400 mg/g creatinine or 5 mg/kg/d, all but the youngest subject had abnormally low citrate excretion (Table I).Regression analyses showed a strong inverse correlation between age and citrate excretion (r = –0.84, P <.0001).

Discussion

Citrate is freely filtered by the renal glomerulus and reabsorbed by a Na+/dicarboxylate co-transporter in the proximal convoluted tubule. Normally, between 65% and 90% of filtered citrate is reabsorbed. Regulation of proximal tubular uptake of citrate appears to be independent of its blood level.15 Non-reabsorbed citrate tends to form a soluble complex with urinary calcium. This ability to chelate calcium prevents precipitation of calcium salts in the urine; citrate thereby serves as an

Acknowledgements

We thank the nursing staff and dietitians of the Clinical Research Center and the technologists of the Endocrinology and General Clinical Research Center laboratories for their contributions to the care of these patients. We also thank David Zurakowski, PhD, for statistical advice.

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    Hepato-nephromegalia glykogenica (Glykogenspeicherkrankheit der Leber und Nieren).

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    *

    Supported by a Clinical Research Center Grant from the Public Health Service Division of Research Resources, NIH M01RR02172, and by the Children’s Hospital–Harvard Medical School Glycogen Storage Disease Research Fund. David Weinstein is funded in part by the National Institutes of Health training grant 5T32 DK07699.

    **

    Reprint requests: David A. Weinstein, MD, Division of Endocrinology, Children’s Hospital, 300 Longwood Ave, Boston, MA 02115.

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