Lyme Neuroborreliosis is a Severe and Frequent Neurological Disease in Mexico.

OBJECTIVE: To describe clinical cases with neurological manifestations associated with Borrelia burgdorferi infection in a large cohort of children and adults from Mexico. MATERIAL AND METHODS: Patients with neurological manifestation (cranial neuritis, radiculoneuritis, meningitis and encephalomyelitis) were recruited in one pediatric and two general hospitals, during January 2006-December 2015. Blood and cerebrospinal fluid (CSF) samples were drawn from each patient at inclusion. IgM and IgG antibodies against B. burgdorferi were detected using a commercial ELISA test, and confirmed by Western-Blot test (WB) using three different antigens from Borrelia burgdorferi complex. Following CDC criteria were considered true cases with both positive tests. RESULTS: Of 606 patients recruited, 403 (66.5%) were adults and 203 (33.4%) children, 50.5% were male. B. burgdorferi infection was diagnosed in 168 patients (27.7%), 97 adults, mean age 42 ± 14.7 years and 71 children, mean age 9.6 ± 5 years; early disseminated disease occurred in 130 cases (77.4 %) and chronic stage in 38 (22.6 %). A previous tick bite was reported by 21% cases, and 5% recalled an erythema migrans lesion. Polyradiculoneuropathy and encephalomyelitis were the most common manifestations, whereas 14.8% presented an initial Guillain-Barré Syndrome. B. burgdorferi sensu stricto was identified in 142 (84%) cases, B. garinii in 14 (8%), B. afzelii in three, and nine cases presented coinfection with two species. CONCLUSION: Lyme neuroborreliosis is a frequent condition in patients with neurological diseases in Mexico.

[Menstrual pattern characteristics in female adolescents with epilepsy]. / Características del patrón menstrual en adolescentes con epilepsia.

BACKGROUND: There are multiple adverse effects from anti-epileptic drugs, including menstrual irregularities such as amenorrhea, oligomenorrhea, gynecomastia, galactorrhea and polycystic ovary syndrome. In view of the paucity of information, the purpose of this study was to determine the frequency of menstrual disorders in female adolescents with epilepsy in a tertiary care pediatric hospital. METHODS: Female adolescents with epilepsy, older than 9 years and with more than 1 year with epilepsy were included. Initially, pubertal stage was identified. During 6 months, menstrual patterns were assessed. Among those with detected menstrual disorders, a hormonal profile and gynecological ultrasound were performed. Statistical analysis was descriptive. RESULTS: 24 patients with a median of 13 years of age; 40 % with overweight or obesity. Most received more than two anti-epileptic drugs. Sixteen patients (66.6 %) had one or more menstrual disorders: 10 had menorrhagia, 6 polymenorrhea, 6 dysmenorrhea, 4 opsomenorrhea; 4 had primary amenorrhea and 1 secondary amenorrhea. There were four patients with hyperprolactinemia and three with hypothyroidism. Evolution time and treatment of epilepsy, as well as the number of anti-epileptic drugs were higher among those with menstrual disorders. CONCLUSIONS: The high frequency of menstrual disorders in female adolescents with epilepsy should be taken into account as part of the comprehensive treatment of these patients.

INTRODUCCIÓN: existen múltiples efectos adversos de los fármacos antiepilépticos, uno de ellos son las irregularidades menstruales como amenorrea, oligomenorrea, ginecomastia, galactorrea y síndrome de ovarios poliquísticos. Ante la poca información, el objetivo de este estudio fue determinar la frecuencia de alteraciones menstruales en adolescentes con epilepsia en un hospital pediátrico de tercer nivel de atención. MÉTODOS: se incluyó a adolescentes con epilepsia, mayores de nueve años de edad y con más de un año con epilepsia. Inicialmente se definió el estadio puberal. Durante seis meses se evaluó el patrón menstrual. Entre quienes se detectó alguna alteración se evaluó perfil hormonal y se realizó ultrasonido ginecológico. El análisis fue descriptivo. RESULTADOS: 24 pacientes con una mediana de 13 años; 40 % con sobrepeso u obesidad. La mayoría recibía más de dos fármacos antiepilépticos; 16 pacientes (66.6 %) tuvieron uno o más trastornos menstruales: 10 hipermenorrea, seis polimenorrea, seis dismenorrea, cuatro opsomenorrea; dos tuvieron amenorrea primaria y una amenorrea secundaria; cuatro presentaron hiperprolactinemia y tres, hipotiroidismo. El tiempo de evolución y de tratamiento de la epilepsia, así como el número de fármacos antiepilépticos fueron mayores entre quienes tenían trastornos menstruales. CONCLUSIONES: la alta frecuencia de trastornos menstruales en adolescentes con epilepsia debe tomarse en cuenta como parte del tratamiento integral de estas pacientes.

Mutational analysis of the LDL receptor and APOB genes in Mexican individuals with autosomal dominant hypercholesterolemia.

The goal of this project was to identify families with autosomal dominant hypercholesterolemia (ADH) to facilitate early detection and treatment and to provide genetic counselling as well as to approximate the mutational diversity of ADH in Mexico. Mutational analysis of the LDLR and APOB genes in 62 index cases with a clinical and/or biochemical diagnosis of ADH was performed. Twenty-five mutations (24 LDLR, 1 APOB) were identified in 38 index cases. A total of 162 individuals with ADH were identified using familial segregation analysis performed in 269 relatives of the index cases. In addition, a novel PCSK9 mutation, c.1850 C>A (p.Ala617Asp), was detected. The LDLR mutations showed the following characteristics: (1) four mutations are novel: c.695 -1G>T, c.1034_1035insA, c.1586 G>A, c.2264_2273del; (2) the most common mutations were c.682 G>A (FH-Mexico), c.1055 G>A (FH-Mexico 2), and c.1090 T>C (FH-Mexico 3); (3) five mutations were identified in 3 or more apparently unrelated probands; (4) three mutations were observed in a true homozygous state; and (5) four index cases were compound heterozygous, and one was a carrier of two mutations in the same allele. These results suggest that, in Mexico, ADH exhibits allelic heterogeneity with 5 relatively common LDLR mutations and that mutations in the APOB gene are not a common cause of ADH. This knowledge is important for the genotype-phenotype correlation and for optimising both cholesterol lowering therapies and mutational analysis protocols. In addition, these data contribute to the understanding of the molecular basis of ADH in Mexico.

G6PD (AC)n and (CTT)n microsatellites in Mexican Mestizos with common G6PD African variants.

Genotyping for the G6PD (AC)n and (CTT)n microsatellites in a sample of 58 Mexican Mestizos with common G6PD African variants was carried out. The second mutation that defines to the variants G6PD A(-202A/376G), G6PD Santamaria(376G/542T) and G6PD A(-376G/968C) very probably occurred on G6PD A(376G) chromosomes with the compound haplotypes, intragenic silent polymorphisms and microsatellites, Pvu-II/Pst-I/Bcl-I/Nla-III/(AC)n/(CTT)n: +/+/-/+/166 bp/195 bp, -/+/-/+/166 bp/201 bp, and -/+/-/+/166 bp/204 bp respectively. The structure of the repeat sequences for the AC-166 bp allele in the 3 variants was (TA)5(AA)1(TA)9(CA)10 whereas the repeat sequences for the CTT-195 bp, CTT-201 bp and CTT-204 bp alleles were (CTT)11(ATT)6, (CTT)7(ATT)12 and (CTT)7(ATT)13 in the first, second and third variants respectively. Genotyping for the G6PD microsatellites can be a useful tool with several applications.

DNA sequencing analysis of several G6PD variants previously defined by PCR-restriction enzyme analysis

Results of a corroborative DNA sequencing analysis for five glucose-6-phosphate dehydrogenase (G6PD) mutations previously defined by PCR-restriction enzyme analysis are presented. The suitability for performing DNA sequencing analysis is discussed along with the importance of selecting the proper PCR-REA strategy in order to define the presence of a specific mutation .

Glucose-6-phosphate dehydrogenase (G-6-PD) mutations in Mexico: four new G-6-PD variants.

Screening for mutations at the G-6-PD gene by PCR-SSCP combined with restriction enzyme analysis and DNA sequencing was performed in nine G-6-PD deficient individuals with negative results for the presence of the most frequent G-6-PD mutations previously observed in Mexican population. The variants G-6-PD Valladolid(406T), G-6-PD Durham(713G), and G-6-PD Viangchan(871A) and four new G-6-PD mutant alleles were identified. The new mutations are located at cDNA nt 376 A --> T (126 Asn --> Tyr), nt 770 G --> T (257 Arg --> Leu), nt 1094 G --> A (365 Arg --> His), and nt 1285 A --> G (429 Lys --> Glu) and they were named G-6-PD San Luis Potosi, G-6-PD Zacatecas, G-6-PD Veracruz, and G-6-PD Yucatán, respectively. To date, a total of 18 different G-6-PD variants have been observed in Mexico and several of them are common in Africa, South Europe, and Southeast Asia.

Molecular heterogeneity of glucose-6-phosphate dehydrogenase deficiency in Mexico: overall results of a 7-year project.

Several years ago, a project aiming to determine (i) the molecular basis of G-6-PD deficiency, (ii) the distribution of four different mutant alleles previously detected, and (iii) the whole of polymorphic alleles that account for the overall prevalence of G-6-PD deficiency in Mexico was implemented. Nearly 5000 individuals-from the general population and patients with hemolytic anemia-belonging to at least 14 States were screened for G-6-PD deficiency. Seventy-six G-6-PD-deficient subjects were detected and the prevalence of G-6-PD deficiency in 4777 individuals from the general population was 0.71%. Screening for both mutations associated with enzyme deficiency and silent polymorphisms at the G-6-PD gene was performed in the enzyme-deficient individuals by PCR-SSCP combined with restriction enzyme analysis; the silent polymorphisms as well as the nondeficient variant G-6-PD A(376G) were also investigated in 366 G-6-PD normal individuals from the general population. In 88% of the enzyme-deficient individuals it was possible to define the mutation responsible and the type G-6-PD A- variants were the more common in both individuals from the general population and patients with hemolytic anemia. G-6-PD deficiency is heterogeneous at the DNA level in Mexico and up to date 10 different variants-8 in the present project and 2 previously-have been observed: G-6-PD A(-202A/376G), G-6-PD A(-376G/968C), G-6-PD Santamaria(376G/542T), G-6-PD Vanua Lava(383C), G-6-PD Tsukui(del561-563), G-6-PD "Mexico City"(680A), G-6-PD Seattle(844C), G-6PD Guadalajara(1159T),G-6-PD Nashville(1178A), and G-6-PD Union(1360T). The G-6-PD A(-) variants have a relatively homogeneous distribution and along with G-6-PD Santamaria(376G/542T), they account for 82% of the overall prevalence of G-6-PD deficiency in Mexico; all other seven variants represent 9% of the mutant alleles examined, and in the rest of the chromosomes the mutation responsible for the enzyme deficiency remains to be defined. Several of the variants observed in Mexico are common in Africa, South Europe, and Southeast Asia. The prevalence for the variant G-6-PD A(376G) was 1.64%. From 256 possible haplotypes only 14 were observed and haplotype analysis suggests that some of the G-6-PD variants probably were imported to Mexico by population flow from South Europe, Africa, and Southeast Asia. This work (i) identified the G-6-PD variants prevalent in Mexico, (ii) defines their geographical distribution, (iii) contributes to the knowledge of the genetic structure of the Mexican population, and (iv) will facilitate the molecular analysis of the G-6-PD gene in enzyme-deficient Mexican individuals.

Genotyping by"cold single-strand conformation polymorphism" of the UGT1A1 promoter polymorphism in Mexican mestizos.

Since no data have previously been reported concerning both the (TA) n polymorphism at the promoter of the UGT1A1 gene in the Mexican population and the use of single-strand conformation polymorphism (SSCP) for the detection of such polymorphism, genotyping by SSCP in 375 G-6-PD normal (Group A) and 81 G-6-PD-deficient (Group B) mestizos belonging to 14 states was carried out. Allele frequencies for (TA)6 and (TA)7 repeats were 0.654 and 0.334, respectively, in Group A and 0.685 and 0.315 in Group B; in the former group, the (TA)5 allele was also observed with a frequency of 0.012. The frequencies of the genotype (TA)7/(TA)7 were 10.1% (Group A) and 8.6% (Group B). The (TA)7/(TA)8 genotype was also observed in a patient with unconjugated hyperbilirubinemia. Due to the importance of its potential medical implications, the observed high frequency (10%) of the (TA)7/(TA)7 genotype is stressed. Genotyping by SSCP of the (TA) n polymorphism is an adequate methodological option.

Envenenamiento mortal causado por el aceite de epazote: chenopodium graveolens / Fatal poisoning caused by epazote oil: chenopodium graveolens

Se presenta el caso de una niña de 2 años y 9 meses de edad, a quien una curandera indica la administración de aceite de epazote (aceite de quenopodio) como vermífugo, en dos tomas de 20 ml cada una. Después de la segunda manifiesta coma profundo, convulciones, midriasis, apnea, acidosis metabólica, choque neurogénico y muerte. ElEEG mostró un trazo sugestivo de encefalopatía, la TAC con imagen de edema cerebral y colapso ventricular. El estudio postmortem ratificó el edema cerebral y microscópicamente evidenció necrosis neuronal difusa; otros hallazgos fueron neumonía, enteritis, peicolangitis, pancreatitis incipiente y necrosisi tubular, el análisis fitoquímico del aceite identificó ascaridol, principio activo de las quenopodáceas, en cantidad 39 mg/ml (1,560 mg en los 40 ml ingeridos) y a chenopodium graveolens como la planta de la que se obtuvo el aceite, conforme al método como históricamente se adminstraba el aceite, la paciente debió haber ingerido una dosis total de ascaridol de 60 mg, por lo que la cantidad administrada fue 26 veces superior, además que excedía 56 por ciento la dosis de 1,000 mg, informada como letal en humanos.

Eritroenzimopatías hereditarias en neonatos con hiperbilirrubinemia / Hereditary erythroenzymopathies in neonates with hyperbilirubinemia

Se presentan los resultados del tamizaje para eritroenzimopatías hereditarias en 707 recién nacidos a término con hiperbilirrubinemia (305 niñas y 402 varones), cuyo objetivo fue determinar su frecuencia relativa. Se tamizó por métodos fluorescentes para las eritroenzimopatías más frecuentes a saber: deficiencias de glucosa-6-fosfato deshidrogenasa (G-6-PD), piruvato cinasa (PC) y glucosa fosfatoisomerasa (GPI): estos son tres de los 14 errores congénitos del metabolismo del eritrocito claramente asociados con hemólisis. Se identificaron cuatro varones con deficiencia de G-6-PD y no se encontraron individuos con deficiencia de PC o GPI. Los resultados globales de éste y de estudios previos de nuestro grupo en una población de 2218 individuos sugieren que la frecuencia de la deficiencia de G-6-PD en varones recién nacidos con ictericia y/o hiperbilirrubinemia es de 1.08%. Se concluye que la deficiencia de G-6-PD como causa de hiperbilirrubinemia no es un problema de salud pública en la población estudiada; sin embargo, ya que 1% de los varones con ictericia y/o hiperbilirrubinemia neonatal tienen deficiencia de G-6-PD, se recomienda tomar en consideración este diagnóstico al evaluar a un neonato que presente anemia y/o hiperbilirrubinemia

Las eritroenzimopatias hereditarias: II. Métodos y procedimientos de tamizaje / Heredity red blood cell enzyme disorders. II. Screening methods and procedures

En relación con un programa de detección de eritroenzimopatías, se revisan los métodos y procedimientos de tamizaje. Se han descrito más de 20 diferentes eritroenzimopatías hereditarias. El denominador común en 14 de estas, es la presencia de anemia hemolítica, razón por la cual no es posible distinguir un defecto de otro sin practicar estudios enzimáticos específicos generalmente laboriosos y que requieren de recursos no disponibles en todos los laboratorios. Se presentan nuevos procedimientos enzimáticos de tamizaje por fluorescencia para la detección de eritroenzimopatías hereditarias. Dichos procedimientos se basan en la interdependencia de las vías metabólicas, de tal forma que con un número mínimo de ensayos se prueba la integridad de múltiples reacciones enzimáticas. Estos procedimientos, usados en combinación con otros métodos de tamizaje notificados, hacen posible la detección de las siguientes eritroenzimopatías asociadas con hemólisis: deficiencias de adenilato kinasa, hexokinasa, glucosa-6-fosfato deshidrogenasa, glucosa fosfato isomerasa &P, fosfofructokinasa aldolasa, triosa fosfato isomerasa, fosfoglicerato kinasa, piruvato kinasa gama-glutamilcisteína sintetasa y glutatión sintetasa. Las características de esta metodología son tales que por su versatilidad, sencillez y economía pueden aplicarse en laboratorios con recursos mínimos y harán posible el tamizaje de 11 eritroenzimopatías. Se describen detalladamente cada uno de los métodos y procedimientos de tamizaje; se mencionan los resultados obtenidos con dicha metodología en el programa para la detección de eritroenzimopatías hereditarias y por último se discuten brevemente las diferentes etapas que comprende la detección y caracterización de las eritroenzimopatías hereditarias