Results of this study support the administration of intravitreal pegaptanib as useful therapy in the management of stage 3+ ROP.

Hereditary xanthinuria (HX) is a rare inherited disorder caused by a deficiency of xanthine dehydrogenase/oxidase (XDH/XO). Missing XDH/XO activity leads to undetectable levels of uric acid excessively replaced by xanthine in serum/urine. The allopurinol loading test has been traditionally used to differentiate between HX types I and II. Final confirmation of HX has been based on the biopsy finding of the absent XDH/XO activity in the small intestine or liver. We present the clinical, biochemical, ultrasound and molecular genetics findings in three new patients with HX and suggest a simple three-step approach to be used for diagnosis, typing and confirmation of HX. In the first step, the diagnosis of HX is determined by extremely low serum/urinary uric acid excessively replaced by xanthine. Second, HX is typed using urinary metabolomics. Finally, the results are confirmed by molecular genetics. We advocate for this safe and non-invasive diagnostic algorithm instead of the traditional allopurinol loading test and intestinal or liver biopsy used in the past.

Hereditary vitamin D-resistant rickets (HVDRR) is a rare recessive genetic disorder caused by mutations in the vitamin D receptor (VDR). In this study, we examined the VDR in a young girl with clinical features of HVDRR including rickets, hypophosphatemia, and elevated serum 1,25(OH) 2 D. The girl also had total alopecia. Two mutations were found in the VDR gene: a nonsense mutation (R30X) in the DNAbinding domain and a unique 3-bp in-frame deletion in exon 6 that deleted the codon for lysine at amino acid 246 (DK246). The child and her mother were both heterozygous for the 3-bp deletion, whereas the child and her father were both heterozygous for the R30X mutation. Fibroblasts from the patient were unresponsive to 1,25(OH) 2 D 3 as shown by their failure to induce CYP24A1 gene expression, a marker of 1,25(OH) 2 D 3 responsiveness. [3 H]1,25(OH) 2 D 3 binding and immunoblot analysis showed that the patient's cells expressed the VDRDK246 mutant protein; however, the amount of VDRDK246 mutant protein was significantly reduced compared with wildtype controls. In transactivation assays, the recreated VDRDK246 mutant was unresponsive to 1,25(OH) 2 D 3 . The DK246 mutation abolished heterodimerization of the mutant VDR with RXRa and binding to the coactivators DRIP205 and SRC-1. However, the DK246 mutation did not affect the interaction of the mutant VDR with the corepressor Hairless (HR). In summary, we describe a patient with compound heterozygous mutations in the VDR that results in HVDRR with alopecia. The R30X mutation truncates the VDR, whereas the DK246 mutation prevents heterodimerization with RXR and disrupts coactivator interactions.

Phenylketonuria is an inherited disorder of metabolism of the amino acid phenylalanine caused by a deficit of the enzyme phenylalanine hydroxylase. It is treated with a low-protein diet containing a low content of phenylalanine to prevent mental affection of the patient. Because of the restricted intake of high-biologic-value protein, patients with phenylketonuria may have lower than normal serum concentrations of pre-albumin, selenium, zinc and iron. The objective of the present study was to assess the compliance of our phenylketonuric (PKU) and hyperphenylalaninemic (HPA) patients; to determine the concentration of serum pre-albumin, selenium, zinc and iron to discover the potential correlation between the amount of proteins in food and their metabolic control. We studied 174 patients of which 113 were children (age 1-18), 60 with PKU and 53 with HPA and 61 were adults (age 18-42), 51 with PKU and 10 with HPA. We did not prove a statistically significant difference in the concentration of serum pre-albumin, zinc and iron among the respective groups. We proved statistically significant difference in serum selenium concentrations of adult PKU and HPA patients (p = 0.006; Mann-Whitney U test). These results suggest that controlled low-protein diet in phenylketonuria and hyperphenylalaninemia may cause serum selenium deficiency in adult patients.