Nearly all mutations in the presenilin 1 (PSEN1), presenilin 2 (PSEN2), and amyloid b precursor protein (APP) genes lead to early-onset Alzheimer disease (EOAD, onset age at or before 65 years). In order to assess the genetic contribution of these genes in a series of Colombian AD cases, we performed a systematic mutation analysis in 11 autosomal dominant, 23 familial, and 42 sporadic AD patients (34% with age of onset 65 years). No APP missense mutations were identi®ed. In three autosomal dominant cases (27.2%), two different PSEN1 missense mutations were identi®ed. Both PSEN1 mutations are missense mutations that occurred in early-onset autosomal AD cases: an I143T mutation in one case (onset age 30 years) and an E280A mutation in two other cases (onset ages 35 and 42 years). In addition, a novel PSEN1 V94M mutation was present in one early-onset AD case without known family history (onset age 53 years) and absent in 53 controls. The E318G polymorphism was present in ®ve AD cases and absent in controls. In PSEN2, two different silent mutations were detected, including one not reported elsewhere (P129). The majority of the Colombian AD cases, predominantly late-onset, were negative for PSEN and APP mutations.

We present 19 patients with tuberous sclerosis complex and subependymal giant cell astrocytoma. The mean age at the time of tumor diagnosis was 9.4 years (range, 1.5 to 21 years). Computed cranial tomography (CT) or cranial magnetic resonance imaging (MRI) identified the lesion which was resected in all cases. Seven patients had hydrocephalus and there was an interval increase in the tumor size or a large tumor without hydrocephalus in 12 patients. Surgical criteria included: (1) presence of hydrocephalus; (2) interval increase in tumor size; (3) new focal neurologic deficit attributable to the tumor; and/or (4) symptoms of increased intracranial pressure. Eight patients were identified through a surveillance program involving annual computed cranial tomography. All of these eight patients had their tumor removed prior to the development of symptoms, none had neurologic deficits which persisted after surgery, and none has so far developed recurrent subependymal giant cell astrocytoma. In contrast, of the 11 patients from the non-surveillance group 7 were symptomatic at tumor diagnosis, 1 had a complicated postoperative course, 2 developed recurrent giant cell astrocytoma, and 1 had an extensive lesion that could not be completely excised. Periodic cranial imaging may help to identify subependymal giant cell astrocytomas in tuberous sclerosis patients before they become symptomatic. Earlier diagnosis and treatment could reduce surgical morbidity and the risk of tumor recurrence.

We report three cases of folinic acid-responsive intractable neonatal seizures. All patients were born at term following normal gestation and delivery. In the first infant, seizures began on the 5th day of life and were unresponsive to phenobarbital, pyridoxine, and valproate, but stopped within 24 hours of initiation of folinic acid treatment at the age of 6 months. Her sibling had died at age 6 months with intractable seizures. In the second infant, seizures began in the 2nd hour of life. These were initially controlled with phenobarbital; however, at 3 months of age she developed status epilepticus refractory to anticonvulsants, steroids, and pyridoxine and she required repeated induction of pentobarbital coma. Seizures stopped within 24 hours of starting folinic acid. Seizures and encephalopathy were noted in the third infant on the 2nd day of life. These were controlled with phenobarbital, but at 8 weeks of age seizures recurred and were difficult to control despite the addition of phenytoin. Immediately after folinic acid was initiated the seizures stopped. Breakthrough seizures in all patients have responded to increases in folinic acid; two of the three remain on standard anticonvulsants. All patients have global developmental delay. Cranial magnetic resonance imaging in the second patient shows diffuse atrophy, and in the third patient shows increased signal on T2 images in the white matter of the frontal and parietal lobes. Analysis of cerebrospinal fluid from these patients using high-performance liquid chromatography with electrochemical detection has consistently revealed an as-yet unidentified compound, which can be used as a marker for this condition. We suggest that cerebrospinal fluid be analyzed for the presence of this compound and a trial of folinic acid be considered in neonates with unexplained early onset intractable seizures.

-Objective: As the strength of the association between the APOE ε4 allele and Alzheimers disease (AD) varies across ethnic groups, we studied if there was such an association in Colombian patients. Method: We performed apolipoprotein E (APOE) genotyping in a clinical sample of 83 unrelated AD patients, predominantly late-onset (>65 yrs) including familial ( n =30) and sporadic AD cases (n= 53) diagnosed according to NINCDS-ADRDA criteria and assessed by a multi-disciplinary team. Control subjects (n = 44) had no significant cognitive impairment by medical interview and neuro-psychological testing. Results: We found a high association (OR= 5.1 95%CI 1.9 -13.6) between APOE ε4 and AD, in this series with predominantly late-onset cases with familial aggregation in 24 cases (28.9%). A significant negative association was found between ε2 and AD (OR= 0.2 95% CI 0.05-0.75). Conclusion: Further population-based surveys in Colombia are warranted to precise a possible dose effect of APOE ε4.KEY WORDS: Alzheimers disease, APOE, dementia, risk factors, ethnic groups, Colombia.Asociación positiva entre apoe ε ε ε ε ε4 y demencia de Alzheimer en una serie clinica en Bogotá (Colombia) y revision de los estudios latinoamericanos RESUMEN -Objetivo: Como la fortaleza de la asociación entre el alelo ε4 del gen APOE y la enfermedad de Alzheimer (EA) difiere entre grupos étnicos, quisimos evaluar si esta asociación existe en pacientes colombianos. Métodos: Realizamos una genotipificación para el gen de la apolipoproteina E (APOE) en una muestra clínica de 83 pacientes con EA no relacionados, de inicio predominantemente tardío (> 65 años), incluyendo casos familiares (n=30) y esporádicos (n=53) diagnosticados según los criterios del NINCDS-ADRDA y evaluados por un equipo multi-disciplinario. Los sujetos control (n= 44) no presentaban deterioro cognoscitivo de acuerdo con la entrevista médica y la evaluación neuropsicológica. Resultados: Hallamos una alta asociación (OR= 5.1; IC95% 1.9-13.6) entre APOE ε4 y EA en la serie de casos de inicio tardío y con agregación familiar en 24 sujetos (28.9%). Una asociación negativa, estadísticamente significativa, fue encontrada entre ε2 y EA (OR= 0.2; IC95% 0.05-0.75). Conclusión: En Colombia son necesarios futuros estudios con base poblacional para poder precisar la existencia o no de un efecto de dosis de APOE ε4.PALABRAS-CLAVES: enfermedad de Alzheimer, APOE, demencia, factores de riesgo, grupos étnicos, Colombia.