Síndrome de Leigh causado por la mutación G14459A del ADN mitocondrial en una familia mexicana / Leigh syndrome caused by the mitochondrial DNA G14459A mutation in a mexican family

Introducción. El síndrome de Leigh es una enfermedad neurodegenerativa y progresiva, de aparición en la infancia, que está causada por defectos tanto en el genoma nuclear como en el mitocondrial. La mutación G14459A del ADN mitocondrial se ha asociado con anterioridad a la neuropatía óptica hereditaria de Leber y recientemente al síndrome de Leigh. Caso clínico. Niña mexicana de 10 meses de edad diagnosticada, después de un seguimiento clínico, neurológico y radiológico, de síndrome de Leigh. Se le realizó el análisis de mutaciones puntuales en el ADN mitocondrial asociadas a este síndrome, y se encontró la mutación G14459A en un porcentaje próximo a la homoplasmia y en heteroplasmia en la madre. El resto de familiares relacionados por vía materna carecen de la mutación. Conclusión. La mutación G14459A, aunque poco frecuente en la patología, debe de estudiarse en pacientes con síndrome de Leigh que no presentan las mutaciones puntuales más comunes (AU)

Introduction. Leigh syndrome is a neurodegenerative and progressive disease that appears usually in childhood due to defects in nuclear or mitochondrial genome. The mutation G14459A in mitochondrial DNA has been associated previously to Leber hereditary optic neuropathy and recently to Leigh syndrome. Case report. A 10 months-old Mexican girl diagnosed of Leigh syndrome. Molecular-genetic studies detected the mutation G14459A in a percentage close to homoplasmy and in low heteroplasmy in her mother. The rest of the maternally related family members analyzed were negative. Conclusion. The G14459A mutation, although not very frequently associated to Leigh syndrome, should be analyzed in patients that do not present the most common point mutations (AU)

[Leigh syndrome caused by the mitochondrial DNA G14459A mutation in a Mexican family]. / Síndrome de Leigh causado por la mutación G14459A del ADN mitocondrial en una familia mexicana.

INTRODUCTION: Leigh syndrome is a neurodegenerative and progressive disease that appears usually in childhood due to defects in nuclear or mitochondrial genome. The mutation G14459A in mitochondrial DNA has been associated previously to Leber hereditary optic neuropathy and recently to Leigh syndrome. CASE REPORT: A 10 months-old Mexican girl diagnosed of Leigh syndrome. Molecular-genetic studies detected the mutation G14459A in a percentage close to homoplasmy and in low heteroplasmy in her mother. The rest of the maternally related family members analyzed were negative. CONCLUSION: The G14459A mutation, although not very frequently associated to Leigh syndrome, should be analyzed in patients that do not present the most common point mutations.

[Neurological and psychological sequelae in children with acute lymphoblastic leukemia who had received radiotherapy and intrathecal methotrexate]. / Secuelas neurológicas y psicológicas que deja la radioterapia o el metotrexate intratecal en niños con leucemia linfoblástica aguda.

UNLABELLED: Our objective was to compare the neurologic and psychological sequelae of children with acute lymphoblastic leukemia (ALL) after three or more years without antineoplasic treatment who underwent cranial irradiation plus intrathecal methotrexate (Group 1) or just intrathecal methotrexate (Group 2). In both groups, a neurologic evaluation, electroencephalogram (EEG) and cranial computed tomography (CCT) were performed. Intellectual quotient and the Bender test were done for the psychological evaluation. Investigators did not know the kind of treatment of each patient. STATISTICS: Fisher's exact test and Mann-Whitney U. There were fourteen patients in group 1 and eight patients in group 2. Intellectual quotient was statistically lower in the first group (median 83.5) than in the second (90.5). Neurologic impairments were found in one patient of each group, alterations of the EEG were found in 6 and 4 in group 1 and 2, respectively, and in the CCT of two patients in group 2 without statistical difference. Children with ALL after cranial irradiation have a greater alteration of intellectual performance than children with intrathecal methotrexate. Neurologic alterations were seen in both groups.

Cerebral infarction and antiphospholipid syndrome in children.

OBJECTIVE: To investigate the prevalence of antiphospholipid antibodies (aPL) in children with acute cerebral infarction. METHODS: The study was carried out in 10 consecutive patients during the first days of neurological symptoms. aPL detected as lupus anticoagulant or anticardiolipin antibodies (aCL) and natural anticoagulant proteins C, S, and antithrombin III were determined in all patients. RESULTS: Seven patients had acute cerebral infarctions associated with aCL; 4 of these patients had high serum aCL concentrations in 2 different determinations (antiphospholipid syndrome). Two patients had temporary protein C deficiency. In one patient with negative aCL, protein C, S, and antithrombin III determinations were not carried out. No patient had evidence of connective tissue disease or family history of hypercoagulable state. After followup of 15.7 months, no patient had recurrent infarction while taking aspirin. CONCLUSION: Our study demonstrates high prevalence of aCL in children who suffer acute cerebral infarction and our results suggest aspirin may be effective therapy to prevent recurrences.

[Safety in the switching traditional cyclosporin to microemulsion cyclosporin in stable renal transplant patients: cooperative study]. / Seguridad en la conversión de ciclosporina tradicional a ciclosporina como microemulsión en trasplante renal estable: estudio cooperativo.

In an open clinical trial we assessed the tolerance and safety of the 1:1 conversion of traditional cyclosporine A (CyA) to a new cyclosporine formulation based on a microemulsion technology (CyN) in 18 patients with stable renal allografts. 56% patients were female. Median patient age was 40.9 +/- 3.2 years (range 18 to 65). Renal transplantation was performed in 24.1 +/- 4.6 months (range 6 to 67 months), prior to the beginning of the study, and 67% of the transplants were from cadaveric donor. The most frequent underlying renal disease was glomerulonephritis (44.4%). None of the patients entering the study were withdrawn prematurely. After 2 weeks of observation for graft function stability, the study was divided in two phases: I: during 4 weeks the patients received CyA traditional at fixed doses (Mean dose administered 3.056 +/- 0.25 mg/Kg/d) and II: during the consecutive 6 weeks with conversion to CyN, with doses adjustment as required (Mean dose 2.887 +/- 0.21 mg/Kg/d). Clinical events, adverse reactions and laboratory parameters were evaluated. Levels of 100-200 ng/ml measured by monoclonal specific fluorescence polarization immunoassay were considered appropriate. There were no significant changes in physical examination and laboratory parameters between phases. The incidence of adverse reactions reported in phase I was only gingival hypertrophy (5%) which persisted in phase II, qualified as probably related to the cyclosporine, and in phase II tremor in 17%, qualified as definitively related. Both drugs were well tolerated and there was no report of acute rejection during the study. We conclude that the tolerance and safety of the 1:1 conversion of CyA to CyN were confirmed by our results, and considering the improved pharmacokinetic properties of the second, the microemulsion presentation will be used preferentially as immunosuppressive drug in the treatment of stable kidney transplant patients.

Indicaciones y complicaciones del transplante renal. Revision. / Indications and complications of kidney transplantation. Review

El numero de contraindicaciones absolutas del transplante renal ha venido disminuyendo en el transcurso de los anos. En la actualidad solo podemos considerar como tales las siguientes situaciones:infeccion activa, enfermedad maligna reciente, oxalosis primaria y edad muy avanzada. En esta revision tambien se analiza la situacion de los denominados receptores de alto riesgo: edad mayor de 50 anos o menor de 1 ano, historia de enfermedades malignas,enfermedad psiquiatrica, enfermedades sistemicas o extrarenales y enfermedades familiares o metabolicas. En cuanto a las complicaciones se describen solamente las mas comunes. Principalmente las infecciones, por instituir estas la mas comun de las complicaciones y la principal causa de morbilidad y mortalidad. Se discuten tambien otras complicaciones asociadas con los esteroides y otras drogas inmunosupresoras. Finalmente, se discute el problema de la glomerulonephritis recurrente, cuya evidencia histologica parece ser mas frecuente que la presencia de anormalidades en el sedimento urinario o en la funcion renal

Family studies of the HLA system in acute post-streptococcal glomerulonephritis.

Eighteen families (67 siblings) of index cases with acute post-streptococcal glomerulonephritis (APSGN) were typed for HLA-A,B,C,DR antigens. Twenty cases of clinical nephritis and 10 cases of asymptomatic disease with detected among the sibships. In eight families with more than one affected individual comprising 18 sib pairs random segregation of paternal and maternal HLA haplotypes was found (0.5 less than p less than 0.06), but some antigens (CW1, DR3) showed deviation from the expected 1:1 ratio in affected and nonaffected siblings in backcross families. We had previously noticed the existence of Mendelian recessive ratios in APSGN but in the absence of clear evidence for a dominant or recessive mode of inheritance for a putative APSGN susceptibility gene(s), pedigree data were analyzed twice for linkage with HLA using the two genetic models. The data obtained, although not sufficient to reject the hypothesis of linkage, provide no support for it. Comparison of the frequency of 61 HLA antigens among 42 unrelated APSGN patients and 109 controls, showed that HLA-DRW4 is more frequent among the former (pc = 0.0500).