V.M. Navas López

Eficacia y seguridad de tacrolimus oral para el tratamiento de la enfermedad inflamatoria intestinal pediátrica

BACKGROUND In certain clinical situations, such as acute and severe episodes of ulcerative colitis (UC) or Crohns Disease (CD), that do not respond to conventional intravenous steroid treatment, we need potent, fast-acting drugs to induce clinical remission and avoid surgery. OBJECTIVES To evaluate the efficacy and safety of oral tacrolimus treatment of acute and severe UC or CD to induce their remission, and also to assess its efficacy in delaying or avoiding surgery. MATERIAL AND METHODS We present a retrospective study that included all patients under 18 years of age with acute and severe bouts of CD (colonic or ileocolonic location) or UC who were treated with oral tacrolimus at our institution from January 1998 to December 2007. RESULTS We included a total of 8 patients (4 males and 4 females), 6 presented with UC and 2 had CD. The mean age of our patients at the start of the treatment was 11.8 years (range 2.75-16.58 y) and the mean time from diagnosis to the start of tacrolimus therapy was 4 months (range 1-96 m). An initial response was obtained in 50% of patients. Plasma trough levels of tacrolimus remained between 5-11 ng/ml. Six of the eight patients (75%) required surgery. In one patient with UC and in another with CD, surgery was avoided. In 2 of the 6 patients with UC, surgery was postponed beyond 6 months. CONCLUSIONS Tacrolimus is useful in inducing clinical remission in patients with acute and severe bouts of UC or CD, and so can avoid or delay the surgery; it may also be used as a bridging agent until the new maintenance therapy with other immunosuppressants is effective.

Plasma citrulline as a marker of loss of enterocitary mass in coeliac disease in childhood

INTRODUCTION Plasma citrulline is not incorporated in endogenous or exogenous proteins so it is a theoretical marker of villous atrophy. Our aim was to correlate plasma citrulline levels with severity of villous atrophy in celiac patients. METHODS Observational case-control study longitudinal in children 16 month-old to 14 year-old: 48 with untreated celiac disease, 9 celiac children under gluten free diet and 35 non-celiac healthy children. Plasma amino acids concentration is determined, expressed in μmol/L, and so are other clinical and analytical data. RESULTS No statistically significative difference found in the referring to BMI, age or renal function. Small increase in fecal fat in celiac children. Citrulline, arginine and glutamine are significantly lower in cases (17.7 μmol/l, 38.7 μmol/l, 479.6 μmol/l respectively) than in controls (28.9 μmol/l, 56.2 μmol/l, 563.7 μmol/l). Citrulline levels are significantly lower in the severe degrees of atrophy than in mild ones (13.8 μmol/l vs. 19.7 μmol/l, p < 0.05), not happening so with rest of amminoacids. SUMMARY Postabsortive mean of plasma citrulline is a good marker of reduction in enterocyte mass in celiac patients with villous atrophy; secondary reduction in plasma arginine too. Just a small histological alteration in intestinal biopsy is enough to differentiate citrulline in cases and controls and besides it can be seen that high levels of atrophy present with lower plasma citrulline.

Disminución de la densidad mineral ósea y otros factores de riesgo en niños prepuberales con fractura del antebrazo distal

AIM To investigate the relationship between bone mineral density (BMD), age, sex, anthropometric measurements, dietary calcium intake and daily physical activity, in prepubertal children with distal forearm fracture (DFF). METHODS 160 children (80 males, 80 females) 3-10 years of age with DFF; control group of 160 children (age-sex matched) were studied. Age, sex, weight, height, tricipital skin fold thickness (TS), body mass index, daily calcium intake, and level of physical activity (extra-school physical exercise: low <1hour/day, high >1hour/day) registered. BMD assessed by peripheral DXA densitometer. RESULTS Most fractures were caused by mild-moderate precipitating trauma by accidental fall (85.6%), with radius fracture in most cases (87.5%). BMI was higher in patients (19.14 kg/m(2)+/-3.50 vs. 17.46 kg/m(2)+/-2.67; p<0.0001). TS thickness was similar in both groups (20.28 mm+/-8.24 vs. 19.61 mm+/-6.60; p>0.05). Physical activity was lower in study group (extra-school physical activity >1h: 21.25% vs. 46.87%; p<0.001). Daily calcium intake was not associated with DFF incidence (918.75 mg/day+/-338.04 vs. 886.13 mg/day+/-382.77; p>0.05). BMD was lower in fractured children (0.2591 g/cm(2)+/-0.0413 vs. 0.2801 g/cm(2)+/-0.0300; p<0.0001) SUMMARY Our results suggest that significantly reduced bone mineral density, overweight and low physical activity are potential risk factors for fracture of the distal forearm, whilst low dietary intakes of calcium do not seem to be associated. The current epidemic of infantile overweight might explain the increased incidence of fractures of the distal forearm.

Lavados colonicos anterogrados para el estrenimiento refractario en ninos sin encefalopatia

A descriptive review of 12 patients who underwent appendicocecostomy or caecostomy for antegrade colonic lavage from January 2002 to February 2008. There were 9 appendicocecostomies performed patients from 3 to 13 years suffering from myelomeningocele, of which 8 of them had a very good outcome, with one case withdrawn due to poor use by the family. Three caecostomies were performed in non-mentally retarded constipated children. One was an otherwise healthy 7 year-old boy with hard stools since he was 10 months old, in spite of multiple laxative treatments, with normal morphology and function. He had a percutaneous caecostomy five years ago, with some improvement and a good quality of life, but still some occasional partial impactions. Another healthy 12 year-old boy with daily constipation associated faecal incontinence since he was 3 years old (normal manometry and rectal biopsy with signs of mild neuronal dysplasia) had a percutaneous caecostomy performed three years ago, with improvement in the faecal incontinence and better psychological outcome. The last caecostomy patient was an 8-year-old boy, with a similar clinical history and good progress in last three years after placing a Chaits button using an endoscopic procedure. Stubborn constipation continuing into adult life has a negative impact on the social and emotional adaptation of the paediatric patient, affecting family interactions. Antegrade colonic lavage allows independence and improves the quality of life in patients affected by recurrent faecal impactions. This technique needs to be performed on more patients to find out its true effectiveness.

Colestasis intrahepática familiar progresiva tipo 3. Defecto de MDR3

182 An Pediatr (Barc). 2008;69(2):181-96 series publicadas, se presenta entre el 3,75 y el 6,6%4-8 de los casos. Según Bagwell, las HDC con secuestro extralobar presentan una mayor incidencia de malformaciones asociadas (15-50%)9. Sólo existe un caso publicado en la bibliografía de duplicación intestinal y poliesplenia, que necesitó un segundo tiempo quirúrgico para su exéresis5. Queremos recalcar que a pesar del mal pronóstico inicial, la paciente presentó una evolución favorable que permitió su extubación a las 48 h tras la cirugía, y que fue dada de alta de la UCIN a los 13 días. Con respecto a los métodos de diagnóstico prenatal, éstos han demostrado tener una elevada sensibilidad y una baja especificidad10, como vemos en nuestro caso, en que se detectó la HDC y el secuestro pero no las otras malformaciones asociadas.

Acidosis D-láctica en un niño de 10 meses afecto de un síndrome de intestino corto: la rápida sospecha equivale a un rápido tratamiento

Metabolic acidosis is a disorder of the acid--base balance which may be due to bicarbonate losses, deficient acid elimination by the kidney, exogenous intake of acids or an endogenous increased acid production. Within this last group, lactic acidosis should be noted, because of its frequency, morbidity and potential mortality. Lactic acidosis, which is generally caused by accumulation of the l-lactic isomer, can be congenital or secondary, the latter is in relation to tissue hypoxia (type A) or to hepatic, renal or oncologic diseases, intense exercise, seizures or toxics (type B). Less common are the situations where the cumulative isomer is the d-lactic, which have occasionally been reported in patients suffering from short bowel syndrome (SBS), presenting with a metabolic acidosis, increased anion GAP and neurological symptoms. We present a case of a ten month old infant with SBS secondary to gastroschisis and intestinal necrosis. He had undergone surgery three times during the neonatal period with a remaining small bowel of 30 cm preserving the ileocecal valve. The patient’s diet was composed of extensively hydrolysed lactose-free formula, gluten-free cereal, vegetables and chicken. Feeding was done mostly through nasogastric tube, with some participation of oral feeding. Metronidazole 20 mg/kg/day and cefixime 8 mg/kg/day were administered alternatively the first week of each month as intestinal decontamination protocol. The month before admission, abundant stool production with decreased consistency associated to weight loss was present. Coincidentally, the decontamination protocol was not followed and 48 h prior to admission, he developed a respiratory syncytial virus respiratory tract infection. On admission, the anthropometric data showed severe malnutrition: weight 4.41 kg (<P1, −5.2 DE), height 63 cm (<P1, −4.62), based on Fernández et al., 2011 standards. Shukla nutritional index was 50.65%. Poor general condition, severe malnutrition and dehydration signs were appreciated. Tachypnea, altered level of consciousness and generalized hypotonia were also present. Severe metabolic acidosis was noted (pH 6.8, bicarbonate 4.3 mmol/L) and the anion GAP was increased (27 mEq/L) with normal lactic levels (0.7 mmol/L). Ketonuria was absent. Correction therapy was started with intravenous fluids containing bicarbonate and

Carta al editorHemocromatosis neonatal: un nuevo y esperanzador horizonteNeonatal haemochromatosis: a new and promising horizon

1. Satischandra P. Hot-Water Epilepsy. Epilepsia. 2003;44 Suppl 1:29—32. 2. Bebek N, Gurses C, Gokyigit A, et al. Hot-water epilepsy: clinical and electrophysiological fidings based on 21 cases. Epilepsia. 2001;42:1130—4. 3. Argumosa A, Herranz JL, Barrasa J, Arteaga R. Epilepsia refleja por agua caliente: un Nuevo caso y revision de la bibliografia. Rev Neurol. 2002;35:349—53. 4. Yavuz ST, Ak M. Hot water epilepsy: case report and review of the literature. AJCI. 2007;1:122—4. 5. Ratnapriya R, Satishchandra P, Dilip S, Gadre G, Anand A. Familial autosomal dominant reflex epilepsy triggered by hot water maps to 4q24—q28. Hum Genet. 2009;126:677—83. 6. Ratnapriya R, Satishchandra P, Kumar SD, Gadre G, Reddy R, Anand A. A locus for autosomal dominant reflex epilepsy precipitated by hot water maps at chromosome 10q21. 3—q22. 3. Hum Genet. 2009;125:541—9. 7. Franzoni E, Gentile V, Grosso S, Brunetto D, Cordelli DM, Balestri P. Bathing epilepsy: report of two Caucasian cases. Epileptic Disord. 2010;12:88—90. 8. Nechay A, John BP. Stephenson, Bath-induced paroxysmal disorders in infancy. Eur J Paediatr Neurol. 2009;13:203—8. 9. Ioos C, Fohlen M, Villeneuve N, et al. Hot Water epilepsy: a benign and unrecognized form. J Child Neurol. 2000;15:125—8. 10. Tezer FI, Ertas N, Yalcin D, Saygi S. Hot water epilepsy with cerebral lesion: a report of five cases with cranial MRI findings. Epilepsy Behav. 2006;8:672—6.

Hemocromatosis neonatal: un nuevo y esperanzador horizonte

1. Satischandra P. Hot-Water Epilepsy. Epilepsia. 2003;44 Suppl 1:29—32. 2. Bebek N, Gurses C, Gokyigit A, et al. Hot-water epilepsy: clinical and electrophysiological fidings based on 21 cases. Epilepsia. 2001;42:1130—4. 3. Argumosa A, Herranz JL, Barrasa J, Arteaga R. Epilepsia refleja por agua caliente: un Nuevo caso y revision de la bibliografia. Rev Neurol. 2002;35:349—53. 4. Yavuz ST, Ak M. Hot water epilepsy: case report and review of the literature. AJCI. 2007;1:122—4. 5. Ratnapriya R, Satishchandra P, Dilip S, Gadre G, Anand A. Familial autosomal dominant reflex epilepsy triggered by hot water maps to 4q24—q28. Hum Genet. 2009;126:677—83. 6. Ratnapriya R, Satishchandra P, Kumar SD, Gadre G, Reddy R, Anand A. A locus for autosomal dominant reflex epilepsy precipitated by hot water maps at chromosome 10q21. 3—q22. 3. Hum Genet. 2009;125:541—9. 7. Franzoni E, Gentile V, Grosso S, Brunetto D, Cordelli DM, Balestri P. Bathing epilepsy: report of two Caucasian cases. Epileptic Disord. 2010;12:88—90. 8. Nechay A, John BP. Stephenson, Bath-induced paroxysmal disorders in infancy. Eur J Paediatr Neurol. 2009;13:203—8. 9. Ioos C, Fohlen M, Villeneuve N, et al. Hot Water epilepsy: a benign and unrecognized form. J Child Neurol. 2000;15:125—8. 10. Tezer FI, Ertas N, Yalcin D, Saygi S. Hot water epilepsy with cerebral lesion: a report of five cases with cranial MRI findings. Epilepsy Behav. 2006;8:672—6.

88 Use of Statins in Children

Introduction Referring to the use of statins for hyperlipemia in children, it is not yet clearly defined who must be treated (recent recommendations focused on older than 8 years) and also the frequency of short and long-term toxicity. Methods Retrospective, descriptive study of patients, 10 year-old or younger, under statin treatment, followed in our Unit. Epidemiology, treatment and side-effects data were analized. Results Twelve children met inclusion criteria; 7/12 female and 11/12 caucasian. Main diagnosis was familiar hypercholesterolemia (10/12); 1/12 hypertriglyceridemia and 1/12 nefrotic syndrome. Positive family history of cardiovascular events: 5/12 (no death among first degree relatives). Mean age at diagnosis was 5.3 years. All of them were asymptomatic. 8/12 had been treated previously (7/12 resins, 1/12 cholesterol absorption inhibitor). Statin treatment starting age was 8.6 years, 4/12 younger than 8 year-old (minimum age: 5.2 years). Atorvastatin used in 10/12, lovastatin 1/12, simvastatin 1/12; initial dose was always 10 mg/day. The average levels before treatment were: LDL 235 mg/dL, total cholesterol 324.7 mg/dL. In one 10 year-old patient (40 mg/day lovastatin) muscular pain was reported with a CPK increase; side-effects stopped once the statin dose was reduced to 20mg/day. Besides, no adverse effect was reported. The highest dose achieved was 40 mg/day. Patients follow-up varies from 9 months to 4 years. Conclusions It remains unclear whether statins could be started before 8 year-old. From our experience, no adverse effects were found in that group. Dose had to be increased to 20–40 mg/day in order to achieve objectives.

1031 Aminoacidopathies: Review and Data of 12 Years Experience from a Spanish Tertiary Care Center

Background/Aims Range and severity of symptoms hugely variable in aminoacidopathies, mainly diagnosed during acute episodes. Tandem Mass spectrometry (Ms/Ms) used in our unit since 2010 for diagnosing asymptomatic infants (very important for prognosis). Methods Retrospective, descriptive study in which field data were collected from clinical histories of patients diagnosed of aminoacidopathies (excluding phenylcetonuria) since 2000 till 2012. Results 30 children detected. 22/30 male; 24/30 caucasians. 10/30 diagnosed by newborn screening, all of them asymptomatic: 1 methylmalonic acidemia (MMA), 3 glutaric aciduria type 1, 2 homocystinuria, 2 methylcrotonylglycinuria, 1 hipermetioninemia and 1 maple syrup urine disease. 20/30 diagnosed because of clinical symptoms, 2/20 since MS/MS newborn screening was performed. Mean age of clinical debut in intoxication type aminoacidopathies was 64.5 days (median 8 days). Most frequent symptoms were clouding of consciousness (9/20), convulsions (2/20) and apnoea (2/20). Laboratory results showed metabolic acidosis (6/20), hyperammonemia (8/20), coagulation defects (4/20) and hipoglycemia. Main complications were: shock (9/20), multiple organ failure (5/20), coagulopathy (4/20), brain injury (1/20), liver failure (1/20) and seizures (2/20). The final diagnosis was: 5 OTC-defficiency, 2 citrullinemia, 3 methylmalonic acidemia, 1 3-OH-metilglutaric aciduria, 1 glutaric aciduria type 1, 1 metilglutaconic acidemia, 1 trimethylaminuria, 1 propionic acidemia, 2 tyrosinemia and 3 homocystinuria. Ventilatory support needed in 13/20, vasoactive agents 11/20, peritoneal dialysis 8/20, continuous veno-venous haemofiltration 4/20. 8 patients died; among survivors, 2/12 madurative failure, 3/12 serious neurological sequelae, 1/12 liver failure, needing transplantation. Conclusions Aminoacidopathies diagnosed by Ms/Ms start early with treatment. Wide range of presentation symptoms and findings.