Inborn errors of metabolism detectable by tandem mass spectrometry in Egypt: The first newborn screening pilot study.

OBJECTIVES: To estimate the burden of metabolic disorders detectable by tandem mass spectrometry in Egypt, through a pilot expanded newborn screening programme at Cairo University Children's Hospital in 2008, and examining the results of 3,900 clinically at-risk children, investigated at Cairo University Children's Hospital for the same disorders over the past 7 years using the same technology. METHODS: Dried blood spots of 25,276 healthy newborns from three governorates in Upper, Middle, and Lower Egypt were screened, to give a representative sample of the Egyptian newborn population. Based on the pilot study outcomes and the results of clinically suspected children, we estimated the total birth prevalence of tandem mass spectrometry detectable metabolic disorders, and the relative frequency of several individual disorders. RESULTS: Among the healthy newborns, 13 metabolic disorder cases (five phenylketonuria [1:5,000], two methylmalonic acidemia, and isovaleric acidemia [1:12,500], one each of maple syrup urine disease, propionic acidemia, ß-ketothiolase deficiency, and primary carnitine deficiency [1:25,000]) were confirmed, giving a total birth prevalence of 1:1944 live births. Among the clinically suspected children, 235 cases were diagnosed, representing a much wider disease spectrum. CONCLUSIONS: Egypt has one of the highest reported birth prevalence rates for metabolic disorders detectable by tandem mass spectrometry. Early diagnosis and management are crucial for the survival and well-being of affected children. A nationwide NBS programme by tandem mass spectrometry is recommended.

Serum klotho: relation to fibroblast growth factor-23 and other regulators of phosphate metabolism in children with chronic kidney disease.

FGF23 and Klotho synergize to regulate phosphate homeostasis by promoting renal phosphate excretion. Chronic kidney disease (CKD) may be viewed as a state of FGF23 resistance caused by Klotho deficiency. This viewpoint explains several observations on phosphate metabolism in CKD that lack mechanistic insights. Our objectives were to correlate serum klotho and FGF-23 with other variables that regulate phosphate metabolism. We studied 40 patients with CKD on conservative treatment (group A), 44 patients with end-stage renal disease (ESRD) on regular hemodialysis (group B), 40 kidney transplant recipients (KTR) (group C) and 40 healthy controls for measuring serum klotho and FGF-23. Blood samples were withdrawn for measuring the levels of serum Calcium (Ca), Phosphorus (P), alkaline phosphatase (ALP), 1,25 (OH)2 D3, intact parathyroid hormone (PTH), FGF-23 and α klotho. The mean levels of FGF-23 and α klotho in control group were 225.78 ± 111.05 pg/ml (range: 102.4, 418.5) and 6.78 ± 1.90 ng/ml (range: 4, 11), respectively. The mean levels of FGF-23 in the 3 studied groups were 1,034.2 ± 84.6, 1,288.7 ± 131.4 and 1,008.7 ± 117.6 pg/ml, respectively. The median levels of s-klotho in the 3 studied groups were 3.15, 2.3 and 2.95, respectively. It was found that FGF-23 was significantly increased and α klotho was significantly decreased in all patients when compared with those in the control group (p < 0.001, <0.001, respectively). We found that there was a significant inverse correlation between serum Ca and α klotho in the studied groups. There was no significant correlation between FGF-23 and α klotho in the studied groups (p > 0.05). We have shown that circulating s-klotho was not related to FGF-23 in CKD, dialysis and KTR patients. In addition, we demonstrated a novel association between serum Ca and s-klotho that needs to be further studied.