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cognitive and motor functioning. J Nutr 2003;133:1473S-6S.

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deficiency in attention-deficit hyperactivity disorder. Biol Psychiatry 1996;

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K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum,

nickel, silicon, vanadium and zinc.WashingtonDC: National Academy Press;

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Fifty Years Ago in The Journal of PediatricsRENAL GLYCOSURIA: OCCURRENCE IN TWO SIBLINGS AND A REVIEW OF THE LITERATURE

Horowitz L, Schwarger S. J Pediatr 1955;47:634-9

Renal glycosuria is a defect in the reabsorption of glucose by the proximal renal epithelial cells. The hallmark of this

condition is the finding of glucose in the urine without evidence of other renal tubular defects or hyperglycemia. This

condition was first reported late in the nineteenth century, with a number of case reports following the initial report.

In Horowitz and Schwarger’s report on 2 children with renal glycosuria, they described the youngest patient documented

to that point. In the discussion, they reviewed in detail the presumed pathogenesis of glycosuria.

We often marvel at the ability of earlier scientists to predict the pathogenesis of conditions when the available technol-

ogy was not able to elucidate the pathophysiology of a condition. The presumed mechanisms in 1955 for renal glycosuria

were as follows:

1. Decreased phosphorylase in the proximal tubule. The phosphorylases were known to be necessary for the intracellularmetabolism of glucose. Therefore, decreased phosphorylase activity would reduce intracellular glucose utilization and,secondarily, the influx of glucose into cells such as the renal proximal tubule.

2. Hormonal control of the renal threshold. The authors cited changes in the maximal ability of the tubule to reabsorbglucose [Tm] with insulin administration or during pregnancy.

3. Repeated infections of the kidney, leading to impaired function.

Our knowledge of the transport of solutes across the proximal tubule epithelium has evolved considerably since 1955.

Single-nephron micropuncture studies, renal cortical slices, direct catheterization of the renal vessels and the ureters, and

membrane vesicle studies have elucidated a primary role for transporters—membrane bound structures that shuttle solutes

in and out of the cell or cell component (eg, lysozome, mitochondria, nucleus). Further knowledge developed from the

genome project points to the sodium-glucose transporter (SGLT2) as the mutation site that explains the findings of

glucose loss in the urine with normal serum glucose concentrations and no other tubular defects.1 The most recent genome

studies have correlated the mutation site in the gene itself and the presence of homozygosity, complex heterozygosity, or

simple heterozygosity with the severity of the glucose loss. Transporter defects explain other conditions, such as renal

tubular acidosis, cystinosis, cystinuria, and Bartter’s syndrome, to name a few. The Horowitz and Schwarger article

highlights some of the advancements that have occurred over the last 50 years.

Aaron Friedman, MD

Department of Pediatrics, Brown Medical School

Providence, RI 02903YMPD1783

10.1016/j.jpeds.2005.08.066

REFERENCE1. Santer R, Kinner M, Lassen CL, et al. Molecular analysis of the SGLT2 gene in patients with renal glycosuria. J Am Soc Nephrol 2003;14:

2873-82.

Iron And Zinc Supplementation Does Not Improve Parent Or Teacher RatingsOf Behavior In First Grade Mexican Children Exposed To Lead 639