Madrid Newborn Sickle Cell Disease Cohort: clinical outcomes, stroke prevention and survival.

In May 2003, Madrid established the universal newborn screening (NBS) for sickle cell disease (SCD). However, there are no studies resembling the evolution of a SCD neonate cohort followed according to national guidelines in Spain. The aim of this study is to describe the morbimortality and the stroke prevention programme in patients diagnosed by SCD NBS in Madrid. This is a multicentre, observational, prospective cohort study between 2003 and 2018; 187 patients diagnosed with SCD were included (151 HbSS, 6 HbSß0, 27 HbSC, 3 HbSß +), and median follow-up was 5.2 years (0.03-14.9). There were 5 deaths: 2 related to SCD in patients with severe genotype (HbSS/HbSß0). Overall survival reached 95% and SCD-related survival 96.8%. The most frequent events were fever without focus, vaso-occlusive crises and acute chest syndromes. Eight strokes occurred in 5 patients which led to a 90.7% stroke-free survival in severe genotype patients (first stroke rate, 0.54 per 100 patient-years). Transcranial Doppler (TCD) was performed in 95% of eligible patients; 75% of children with pathological TCD remained stroke-free. Regarding HbSS/HbSß0 patients, 50.1% received hydroxyurea and 9.5% haematopoietic stem cell transplantation. This study reflects the evolution of Madrid SCD cohort and provides morbimortality data similar to other developed countries.

Newborn screening for homocystinurias: Recent recommendations versus current practice.

PURPOSE: To assess how the current practice of newborn screening (NBS) for homocystinurias compares with published recommendations. METHODS: Twenty-two of 32 NBS programmes from 18 countries screened for at least one form of homocystinuria. Centres provided pseudonymised NBS data from patients with cystathionine beta-synthase deficiency (CBSD, n = 19), methionine adenosyltransferase I/III deficiency (MATI/IIID, n = 28), combined remethylation disorder (cRMD, n = 56) and isolated remethylation disorder (iRMD), including methylenetetrahydrofolate reductase deficiency (MTHFRD) (n = 8). Markers and decision limits were converted to multiples of the median (MoM) to allow comparison between centres. RESULTS: NBS programmes, algorithms and decision limits varied considerably. Only nine centres used the recommended second-tier marker total homocysteine (tHcy). The median decision limits of all centres were ≥ 2.35 for high and ≤ 0.44 MoM for low methionine, ≥ 1.95 for high and ≤ 0.47 MoM for low methionine/phenylalanine, ≥ 2.54 for high propionylcarnitine and ≥ 2.78 MoM for propionylcarnitine/acetylcarnitine. These decision limits alone had a 100%, 100%, 86% and 84% sensitivity for the detection of CBSD, MATI/IIID, iRMD and cRMD, respectively, but failed to detect six individuals with cRMD. To enhance sensitivity and decrease second-tier testing costs, we further adapted these decision limits using the data of 15 000 healthy newborns. CONCLUSIONS: Due to the favorable outcome of early treated patients, NBS for homocystinurias is recommended. To improve NBS, decision limits should be revised considering the population median. Relevant markers should be combined; use of the postanalytical tools offered by the CLIR project (Collaborative Laboratory Integrated Reports, which considers, for example, birth weight and gestational age) is recommended. tHcy and methylmalonic acid should be implemented as second-tier markers.

[Pharmacological preconditioning with sildenafil of warm ischemic kidneys]. / Precondicionamiento farmacológico con sildenafilo del riñón con isquemia normotérmica.

OBJECTIVES: To evaluate the preconditioning effect of sildenafil administered preoperatively in kidneys subjected to a period of warm ischemia (WI), hypothermic perfusion (HP) or cold storage (CS) and finally, autotransplant (AT). MATERIAL AND METHOD: We studied 6 groups of autotransplanted kidneys: no-WI-inmediate AT (Group A); 45 min of WI + immediate AT (Group B); 45 min of WI + 60 min of HP + autotransplant (Group C); 45 min of WI + 60 min of CS + autotransplant (Group D); 100 mg of oral sildenafil preoperatively + 45 min of WI + autotransplant (Group E); 100 mg of oral sildenafil preoperatively + 45 min of WI+60 min of HP + autotransplant (Group F). Belzer solution was used for HP; UW-Viaspan for CS. Inmediately after the autotransplant (reperfusion period), we recorded in real time for 60 min the values of Renal vascular Flow (RVF) and Renal Vascular Resistance (RVR). Nitric Oxide levels in the cava and renal graft vein were recorded every 15 min during the 60 min of the reperfusion-study period. Conventional & Electronic microscopy were completed after the process. RESULTS: We obtained significant higher values of RVF and lower values of RVR in sildenafil groups (E and F) in comparison to the other groups (A-D) (Table 1). NO levels were also significantly higher in groups E and F (Fig. 1). Groups A, B, E and F showed integrity of tubule and endothelium in comparison to groups C and D in the microscopic study. CONCLUSIONS: We showed a beneficious effect of sildenafil in inmediate post-transplant reperfusion hemodynamic and biochemical parameters of kidneys subjected to a critical period of warm-ischemia.

[Prevalence of frequent recessive diseases in the Spanish population through DNA analyses on samples from the neonatal screening]. / Prevalencia de enfermedades recesivas frecuentes en población española mediante análisis de ADN en muestras del cribado neonatal.

BACKGROUND AND OBJECTIVE: Cystic fibrosis (CF) and the nonclassical forms of congenital adrenal hyperplasia (NC21OHD) are frequent autosomal recessive diseases. Their frequencies in the Caucasian population are the ones applied to the management of the diseases (1:2500 and 1:1000, respectively). The aim of this study was to learn about the adequacy of these figures to the Spanish population. MATERIAL AND METHOD: Study of the recurrent mutation (about 50% of alleles) in each entity, DF508 or Val281Leu, respectively, in 300 anonymous consecutive samples (600 alleles) from the Comunidad de Madrid neonatal screening. PCR specific amplifications of the CFTR and CYP21A2 genes and direct analyses of DF508 and Val281Leu mutations were performed. RESULTS: Allele frequencies of DF508 and Val281Leu were 0.005 and 0.038 (carrier frequencies 1.1% and 7.5%, respectively). Taking into consideration the percentage of these mutations in patient alleles, 48% for CF and for 57% NC21OHD, disease frequencies of about 1:8028 (CF) and 1:230 (NC21OHD) were estimated. The standard error calculated for these data were 0.6% and 1.5%. CONCLUSIONS: We have found that CF is less frequent and NC21OHD more frequent in the Spanish population than in other Caucasian populations.