COVID-19 in children and young adults with moderate/severe inborn errors of immunity in a high burden area in pre-vaccine era.

BACKGROUND: Information regarding inborn error of immunity (IEI) as a risk factor for severe COVID-19 is scarce. We aimed to determine if paediatric patients with moderate/severe IEI got COVID-19 at the same level as the general population, and to describe COVID-19 expression. MATERIAL AND METHODS: We included patients with moderate/severe IEI aged 0-21 years old: cross-sectional study (June2020) to determine the prevalence of COVID-19; prospective study (January2020-January2021) including IEI patients with COVID-19. Assays used: nasopharyngeal swab SARS-CoV-2 PCR and SARS-CoV-2-specific immunoglobulins. RESULTS: Seven from sixty-five patients tested positive (prevalence: 10.7% (7%-13%)) after the first SARS-COV-2 wave and 13/15 patients diagnosed with COVID-19 had an asymptomatic/mild course. CONCLUSIONS: In our area, prevalence of COVID-19 in moderate/severe IEI paediatric patients after the first wave was slightly higher than in the general population. The majority of patients presented a benign course, suggesting a possible protective factor related with age despite IEI.

Lesiones pernióticas y acrales en España durante el confinamiento por COVID: análisis retrospectivo de 12 casos / Chilblain and Acral Purpuric Lesions in Spain during Covid Confinement: Retrospective Analysis of 12 Cases

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Miocardiopatía en pacientes con epidermólisis ampollosa hereditaria / Cardiomyopathy in Patients With Hereditary Bullous Epidermolysis

Introducción y objetivos: En las últimas décadas se ha descrito la asociación entre epidermólisis ampollosa (EA) y miocardiopatía dilatada (MD). Generalmente esta última enfermedad se detecta en fases avanzadas, implicando un peor pronóstico. Nuestro objetivo consistió en determinar la prevalencia de MD en los pacientes con EA vistos en el Hospital San Joan de Déu (Barcelona) desde mayo de 1986 a abril de 2015. Métodos: Estudio descriptivo transversal mediante revisión de las historias clínicas con atención al tipo y subtipos mayores de EA y la existencia o no de MD. Resultados: Se recogieron 57 pacientes con diagnóstico de EA. De ellos 19 presentaban EA simple, 10 EA juntural, 27 EA distrófica (14 EA distrófica dominante y 13 EA distrófica recesiva) y existió un caso de síndrome de Kindler. Solo 2 de los pacientes con EA distrófica recesiva presentaron MD. En 23 de los pacientes con EA existieron factores que podrían tener una relación causal con el potencial desarrollo de MD. Conclusión: La MD puede ser una complicación en los pacientes con EA, mayoritariamente del subtipo de EA distrófica recesiva, por lo que deben hacerse controles periódicos para su temprano diagnóstico y tratamiento (AU)

Introduction and objective: In recent decades, an association has been reported between epidermolysis bullosa (EB) and dilated cardiomyopathy (DC). DC is typically in an advanced phase when detected, leading to a poorer prognosis. Our objective was to determine the prevalence of DC in patients with EB seen in Hospital San Joan de Déu in Barcelona, Spain, between May 1986 and April 2015. Methods: This was a descriptive, cross-sectional chart-review study in which we recorded the type and main subtypes of EB and the presence or absence of DC. Results: Fifty-seven patients with EB were found, 19 with EB simplex, 10 with junctional EB, 27 with dystrophic EB (14 dominant dystrophic and 13 recessive dystrophic), and just 1 with Kindler syndrome. DC was detected in only 2 patients with recessive dystrophic EB. Twenty-three patients had presented factors that could have had a causal relationship with the potential onset of DC. Conclusion: DC is a possible complication of EB, particularly in recessive dystrophic EB. Periodic follow-up should be performed to make an early diagnosis and start treatment (AU)

Cardiomyopathy in Patients With Hereditary Bullous Epidermolysis. / Miocardiopatía en pacientes con epidermólisis ampollosa hereditaria.

INTRODUCTION AND OBJECTIVE: In recent decades, an association has been reported between epidermolysis bullosa (EB) and dilated cardiomyopathy (DC). DC is typically in an advanced phase when detected, leading to a poorer prognosis. Our objective was to determine the prevalence of DC in patients with EB seen in Hospital San Joan de Déu in Barcelona, Spain, between May 1986 and April 2015. METHODS: This was a descriptive, cross-sectional chart-review study in which we recorded the type and main subtypes of EB and the presence or absence of DC. RESULTS: Fifty-seven patients with EB were found, 19 with EB simplex, 10 with junctional EB, 27 with dystrophic EB (14 dominant dystrophic and 13 recessive dystrophic), and just 1 with Kindler syndrome. DC was detected in only 2 patients with recessive dystrophic EB. Twenty-three patients had presented factors that could have had a causal relationship with the potential onset of DC. CONCLUSION: DC is a possible complication of EB, particularly in recessive dystrophic EB. Periodic follow-up should be performed to make an early diagnosis and start treatment.

Outbreak of brainstem encephalitis associated with enterovirus-A71 in Catalonia, Spain (2016): a clinical observational study in a children's reference centre in Catalonia.

OBJECTIVES: To describe the characteristics of an outbreak of brainstem encephalitis and encephalomyelitis related to enterovirus (EV) infection in Catalonia (Spain), a setting in which these manifestations were uncommon. METHODS: Clinical and microbiological data were analysed from patients with neurological symptoms associated with EV detection admitted to a reference paediatric hospital between April and June 2016. RESULTS: Fifty-seven patients were included. Median age was 27.7 months (p25-p75 17.1-37.6). Forty-one (72%) were diagnosed with brainstem encephalitis, seven (12%) with aseptic meningitis, six (11%) with encephalitis, and three (5%) with encephalomyelitis (two out of three with cardiopulmonary failure). Fever, lethargy, and myoclonic jerks were the most common symptoms. Age younger than 12 months, higher white-blood-cell count, and higher procalcitonin levels were associated with cardiopulmonary failure. Using a PAN-EV real-time PCR, EV was detected in faeces and/or nasopharyngeal aspirate in all the patients, but it was found in cerebrospinal fluid only in patients with aseptic meningitis. EV was genotyped in 47 out of 57 and EV-A71 was identified in 40 out of 47, being the only EV type found in patients with brainstem symptoms. Most of the detected EV-A71 strains were subgenogroup C1. Intravenous immunoglobulins were used in 34 patients. Eight cases (14%) were admitted to the intensive care unit. All the patients but three, those with encephalomyelitis, showed a good clinical course and had no significant sequelae. No deaths occurred. CONCLUSIONS: The 2016 outbreak of brainstem encephalitis in Catalonia was associated with EV-A71 subgenogroup C1. Despite the clinical manifestations of serious disease, a favourable outcome was observed in the majority of patients.

Factors associated with severity in invasive community-acquired Staphylococcus aureus infections in children: a prospective European multicentre study.

Staphylococcus aureus is the main pathogen responsible for bone and joint infections worldwide and is also capable of causing pneumonia and other invasive severe diseases. Panton-Valentine leukocidin (PVL) and methicillin-resistant S. aureus (MRSA) have been studied as factors related with severity in these infections. The aims of this study were to describe invasive community-acquired S. aureus (CA-SA) infections and to analyse factors related to severity of disease. Paediatric patients (aged 0-16 years) who had a CA-SA invasive infection were prospectively recruited from 13 centres in 7 European countries. Demographic, clinical and microbiological data were collected. Severe infection was defined as invasive infection leading to death or admission to intensive care due to haemodynamic instability or respiratory failure. A total of 152 children (88 boys) were included. The median age was 7.2 years (interquartile range, 1.3-11.9). Twenty-six (17%) of the 152 patients had a severe infection, including 3 deaths (2%). Prevalence of PVL-positive CA-SA infections was 18.6%, and 7.8% of the isolates were MRSA. The multivariate analysis identified pneumonia (adjusted odds ratio (aOR) 13.39 (95% confidence interval (CI) 4.11-43.56); p 0.008), leukopenia at admission (<3000/mm(3)) (aOR 18.3 (95% CI 1.3-259.9); p 0.03) and PVL-positive infections (aOR 4.69 (95% CI 1.39-15.81); p 0.01) as the only factors independently associated with severe outcome. There were no differences in MRSA prevalence between severe and nonsevere cases (aOR 4.30 (95% CI 0.68- 28.95); p 0.13). Our results show that in European children, PVL is associated with more severe infections, regardless of methicillin resistance.

Diagnóstico mediante 18F-FDG PET/TC de endocarditis infecciosa, estadificación y monitorización de tratamiento antibiótico tras transposición de grandes vasos corregida quirúrgicamente / Diagnosis by 18F-FDG PET/CT of infective endocarditis, staging and monitoring of antibiotic treatment after transposition of surgically corrected great arteries

La endocarditis infecciosa es una de las principales causas de síndrome febril de origen desconocido en pacientes portadores de catéter, marcapasos y dispositivos intravasculares. El diagnóstico se realiza siguiendo los criterios modificados de Duke, basados en el hemocultivo y la ecocardiografía. La identificación de vegetaciones mediante ecocardiografía transesofágica puede ser difícil ante cambios anatómicos previos, especialmente en fases precoces. La tomografía por emisión de positrones con 18Fluorodesoxiglucosa (18F-FDG PET/TC) muestra actividad glucídica aumentada en procesos tumorales, inflamatorios e infecciosos, información funcional que permite la detección de la enfermedad causante del síndrome febril de origen desconocido antes de que aparezcan los cambios estructurales. Una ventaja adicional es la posibilidad de detectar enfermedad infecciosa extracardiaca, dado que es una exploración de cuerpo completo. Un papel prometedor de la 18F-FDG PET/TC es la monitorización de la terapia antimicrobiana en los pacientes diagnosticados de endocarditis infecciosa, valorando la eficacia al finalizar el tratamiento estándar y condicionando una intensificación terapéutica (AU)

Infective endocarditis is one of the leading causes of fever of unknown origin in those patients with intravascular catheters, prosthetic valves or cardiovascular implantable electronic devices. The diagnosis of infective endocarditis is made according to modified Duke criteria, which are based on blood culture and echocardiographic findings. Demonstration of vegetation with the transoesophageal echocardiography may be difficult in these cases with previous anatomical changes, especially in early phases. Positron emission tomography with 18F-fluorodeoxyglucose (18F-FDG PET/CT) is well known to show an increased glucidic metabolism in malignant, inflammatory, and infectious processes. Thus, it provides useful functional imaging that enables the disease causing the fever of unknown origin to be detected well before structural changes are evident. Moreover, 18F-FDG PET/CT helps to detect infectious extra-cardiac involvement, since the whole body is imaged with this technique. 18F-FDG PET/CT may have an additional promising role for the monitoring of response to antimicrobial therapy in patients with established infective endocarditis, thus evaluating standard treatment outcome, as well as evaluating the need for alternative/intensified treatment options (AU)

Diagnosis by (18)F-FDG PET/CT of infective endocarditis, staging and monitoring of antibiotic treatment after transposition of surgically corrected great arteries.

Infective endocarditis is one of the leading causes of fever of unknown origin in those patients with intravascular catheters, prosthetic valves or cardiovascular implantable electronic devices. The diagnosis of infective endocarditis is made according to modified Duke criteria, which are based on blood culture and echocardiographic findings. Demonstration of vegetation with the transoesophageal echocardiography may be difficult in these cases with previous anatomical changes, especially in early phases. Positron emission tomography with (18)F-fluorodeoxyglucose ((18)F-FDG PET/CT) is well known to show an increased glucidic metabolism in malignant, inflammatory, and infectious processes. Thus, it provides useful functional imaging that enables the disease causing the fever of unknown origin to be detected well before structural changes are evident. Moreover, (18)F-FDG PET/CT helps to detect infectious extra-cardiac involvement, since the whole body is imaged with this technique. (18)F-FDG PET/CT may have an additional promising role for the monitoring of response to antimicrobial therapy in patients with established infective endocarditis, thus evaluating standard treatment outcome, as well as evaluating the need for alternative/intensified treatment options.

Retinoschisin gene therapy in photoreceptors, Müller glia or all retinal cells in the Rs1h-/- mouse.

X-linked retinoschisis, a disease characterized by splitting of the retina, is caused by mutations in the retinoschisin gene, which encodes a putative secreted cell adhesion protein. Currently, there is no effective treatment for retinoschisis, though viral vector-mediated gene replacement therapies offer promise. We used intravitreal delivery of three different AAV vectors to target delivery of the RS1 gene to Müller glia, photoreceptors or multiple cell types throughout the retina. Müller glia radially span the entire retina, are accessible from the vitreous, and remain intact throughout progression of the disease. However, photoreceptors, not glia, normally secrete retinoschisin. We compared the efficacy of rescue mediated by retinoschisin secretion from these specific subtypes of retinal cells in the Rs1h-/- mouse model of retinoschisis. Our results indicate that all three vectors deliver the RS1 gene, and that several cell types can secrete retinoschisin, leading to transport of the protein across the retina. The greatest long-term rescue was observed when photoreceptors produce retinoschisin. Similar rescue was observed with photoreceptor-specific or generalized expression, although photoreceptor secretion may contribute to rescue in the latter case. These results collectively point to the importance of cell targeting and appropriate vector choice in the success of retinal gene therapies.

Two novel recessive mutations in KRT14 identified in a cohort of 21 Spanish families with epidermolysis bullosa simplex.

BACKGROUND: Basal epidermolysis bullosa simplex (EBS) is a group of blistering genodermatoses mostly caused by mutations in the keratin genes, KRT5 and KRT14. Recessive mutations represent about 5% of all EBS mutations, being common and specific in populations with high consanguinity, where affected patients show severe phenotypes. OBJECTIVES: To accomplish the first mutational analysis in patients of Spanish origin with EBS and to delineate a comprehensive genotype-phenotype correlation. METHODS: Twenty-one EBS families were analysed. Immunofluorescence mapping at the dermoepidermal junction level was performed on skin biopsies from patients. Mutation screening of the entire coding sequences of KRT5 and KRT14 in genomic DNA was assessed by polymerase chain reaction and direct sequencing. RESULTS: KRT5 or KRT14 causative mutations were identified in 18 of the 21 EBS families. A total of 14 different mutations were disclosed, of which 12 were dominant missense mutations and two truncating recessive mutations. Five of the 14 mutations were novel including three dominant in KRT5 (p.V186E, p.T321P and p.A428T) and two recessive in KRT14 (p.K116X and p.K250RfsX8). The two patients with EBS carrying homozygous recessive mutations were affected by severe phenotypes and belonged to consanguineous families. All five families with the EBS Dowling-Meara subtype carried recurrent mutations affecting the highly conserved ends of the α-helical rod domain of K5 and K14. The seven mutations associated with the localized EBS subtype were widely distributed along the KRT5 and KRT14 genes. Two families with mottled pigmentation carried the P25L mutation in KRT5, commonly associated with this subtype. CONCLUSIONS: This study further confirms the genotype-phenotype correlation established for EBS in other ethnic groups, and is the first in a Mediterranean country (excluding Israel). This study adds two novel recessive mutations to the worldwide record to date, which includes a total of 14 mutations. As in previous reports, the recessive mutations resulted in a lack of keratin K14, giving rise to a generalized and severe presentation.

The relation between obesity, abdominal fat deposit and the angiotensin-converting enzyme gene I/D polymorphism and its association with coronary heart disease.

OBJECTIVE: To analyse the relation between overweight, obesity and fat distribution with I/D polymorphism of the angiotensin-converting enzyme (ACE) gene and its association with coronary heart disease (CHD). DESIGN: Cross-sectional, case-control study. SUBJECTS: A total of 185 cases (141 males) who had suffered at least one episode of CHD and 182 controls (127 males). MEASUREMENTS: Body mass index, waist circumference, blood pressure, plasma total cholesterol, triglycerides, HDL cholesterol and fasting glucose were measured with standard methods, genotyping the I/D polymorphism of ACE gene. RESULTS: Obesity and abdominal fat deposit are associated with CHD in women, but not independently. We have found an association between obesity and abdominal fat deposit with the ACE gene I/D polymorphism in subjects with CHD. Subjects with CHD and DD or ID genotypes have significantly higher prevalence of obesity and abdominal fat deposit and higher values of weight and waist circumference. In addition, the DD and ID genotypes increased crude OR of obesity. The DD and ID genotypes of the ACE gene I/D polymorphism and BMI are independently associated with CHD. CONCLUSION: There is a relation between the type and grade of obesity with the genotypes of the ACE gene I/D polymorphism in subjects with CHD.

Low serum carnitine in HIV-infected children on antiretroviral treatment.

OBJECTIVE: HIV-infection and antiretroviral therapies are associated with energy dysfunction and lipid metabolism in adults. Our aim was to detect a possible carnitine deficiency in HIV-infected children on antiretroviral treatments. We analysed the relation among serum carnitine, its amino-acid precursors (methionine and lysine), clinical evaluation and antiretroviral therapy. DESIGN AND SETTING: Cross-sectional study performed in a tertiary care hospital. SUBJECTS: A total of 79 HIV-infected children on antiretroviral therapy, monitored prospectively in our hospital. INTERVENTIONS: Antiretroviral therapy included nucleoside analogues plus protease inhibitors and/or non-nucleoside analogues. Carnitine was analysed by an enzymatic-spectrometric procedure, and amino acids by ion exchange chromatography. Reference values of carnitine and amino acids were established in apparently healthy children who underwent presurgical analysis for minor surgery. RESULTS: Serum free and total carnitine, acylcarnitines, methionine and lysine were significantly lower in HIV-infected children compared with our reference values for similar ages (P<0.0001; Student's t-test). Low carnitine values were observed in 37% of our HIV-infected children. A significantly positive correlation was observed between serum total carnitine and methionine or lysine (P<0.0001 and P=0.005, respectively; Pearson test). No relation was observed between serum carnitine and clinical stage of HIV infection, immunological or nutritional status or lipodystrophy. Free and total carnitine were significantly lower (P=0.002 and 0.033, respectively) in HIV-infected patients on protease inhibitors (N=56) compared with those on other treatments (N=23). CONCLUSIONS: Low serum carnitine concentration was observed in 37% of our HIV-infected children on antiretroviral therapy. Malabsorption or defective synthesis may also account for the low serum carnitine values detected in these patients.

[Determinants of HIV mother-to-child transmission in Catalonia, Spain [1997-2001]: is it possible to eliminate it?]. / Determinantes de la transmisión vertical del VIH en Cataluña (1997-2001): ¿es posible su eliminación?

OBJECTIVES: To identify and describe the factors that have led to new cases of HIV infection through mother-to-child transmission since the introduction of antiretroviral therapy in HIV-seropositive pregnant women (1997-2001) in Catalonia. METHODS: Systematic review of cases identified in the pediatric services of all the hospitals in Catalonia. RESULTS: Twenty-eight cases of pediatric HIV infection were identified: 9, 9, 8, 2 and 0 per year of birth from 1997 to 2001, respectively. Of 16 mothers with a diagnosis of known HIV infection before or during pregnancy, nine underwent antiretroviral prophylaxis during pregnancy (compliance was good in five, unknown in one and poor in one) and seven did not undergo prophylaxis (six refused it and no information was available in one). Of 12 mothers diagnosed after delivery, pregnancy was not monitored in five and was little or well-monitored in the remaining seven. Of mothers with well-monitored pregnancy, a serological HIV test was not performed in six and was negative in the first trimester in one. CONCLUSIONS: Mother-to-child transmission of HIV has decreased in the last few years in Catalonia, but infections have sometimes occurred through poor implementation of preventive measures. Pregnant women should be offered an HIV diagnostic test not only in the first trimester but also at the end of pregnancy if HIV exposure is suspected. In women with unmonitored pregnancies, rapid diagnostic tests for HIV should be used in the delivery room.

Determinantes de la transmisión vertical del VIH en Cataluña(1997-2001): ¿es posible su eliminación? / Determinants of HIV mother-to-child transmission in Catalonia, Spain [1997-2001]: is it possible to eliminate it?

Objetivos: Identificar y describir los factores que han hecho posible la existencia de nuevas infecciones de VIH por transmisión vertical desde la implementación del tratamiento antirretroviral en la gestante seropositiva (1997-2001) en Cataluña.Métodos: Revisión sistemática de casos identificados en servicios de pediatría de todos los hospitales de Cataluña.Resultados: Se identificaron 28 casos de infección pediátrica por VIH: 9, 9, 8, 2 y 0 por año de nacimiento de 1997 a 2001, respectivamente. De 16 madres con diagnóstico de infección por VIH conocido antes o durante el embarazo, 9 realizaron profilaxis antirretroviral durante éste (5 con buena adhesión, uno desconocido y el resto con mala adhesión) y 7 no realizaron profilaxis (6 por rechazo y uno no se conoce).De 12 diagnosticadas después del parto, 5 fueron embarazos no controlados y el resto poco o bien controlados. De estos últimos, en 6 no se practicó serología para VIH y en uno fue negativa en el primer trimestre.Conclusiones: La transmisión vertical del VIH en Cataluña ha disminuido en los últimos años, pero se han producido infecciones por la mala implementación en algún caso de las medidas preventivas conocidas. Debería ofrecerse la prueba diagnóstica para VIH a toda gestante no sólo en el primer trimestre de embarazo sino también al final, si se sospecha exposición al virus, y en caso de gestaciones no controladas hay que usar pruebas diagnósticas de lectura rápida en la sala de partos. (AU)

[Neurofibromatosis type 2 as a result of a de novo mutation: a case report]. / Neurofibromatosis tipo 2 por mutación de novo. A propósito de un caso.

INTRODUCTION: Neurofibromatosis type 2 is a dominant autosomic hereditary disease which courses with distinct tumours of the central nervous system and scant cutaneous manifestations. The increased knowledge of the natural history and the genetics of NF 2 acquired over the past few years has shown that clinical onset possibly occurs during the paediatric age and an early diagnosis of these patients can be decisive in the final outcome. CLINICAL CASE: A 12 year old girl who visited the clinic because of a month old presentation of cervical tumour, otalgia and dysphonia. Exploration revealed signs of cranial nerve disorder and the magnetic resonance (MR) showed bilateral schwannomas of the eighth cranial nerves. The extension study showed ocular, auditory, troncoencephalic and cervical spinal cord disorders. The patient died three months after hospital admission. The genetic study showed a de novo mutation in the NF 2 gene (chromosome 22q12). DISCUSSION: The identification of the various mutations that cause NF 2 has enabled the early diagnosis of the patient s relatives. However, there are still patients who have not been confirmed genetically. Furthermore, de novo mutations are not predictable. NF 2 diagnosis is still clinical. In the last few years, two disease phenotypes have been defined: mild and moderate/serious, which is associated with an early onset and de novo mutations. The high incidence rate of cataracts and other associated tumours, such as those affecting paraspinal and cutaneous areas together with meningiomas, which up until now could have gone unnoticed, has also been observed. Clinical onset in the paediatric age is more frequent than was expected and shows distinct and subtle symptoms.

Neurofibromatosis tipo 2 por mutación de novo.A propósito de un caso / Neurofibromatosis type 2 as a result of a de novo mutation: a case report

Introducción. La neurofibromatosis tipo 2 (NF-2) es una enfermedad de herencia autosómica dominante que cursa con distintos tumores del sistema nervioso central y escasas manifestaciones cutáneas. El mayor conocimiento de la historia natural y de la genética de la NF-2 en los últimos años ha demostrado la posibilidad que se inicie clínicamente en la edad pediátrica; el diagnóstico precoz de estos enfermos puede ser decisivo para su pronóstico final. Caso clínico. Niña de 12 años que consulta por tumoración cervical, otalgia y disfonía de un mes de evolución. La exploración revela signos de afectación de pares craneales y la resonancia magnética es demostrativa de schwannomas bilaterales del octavo par craneal. El estudio de extensión muestra una afectación ocular, auditiva, troncoencefálica y de la médula cervical. La paciente falleció a los tres meses del ingreso. El estudio genético demostró una mutación de novo en el gen de la NF-2 (cromosoma 22q12). Conclusiones. La identificación de varias mutaciones causantes de NF-2 ha permitido el diagnóstico precoz de familiares de enfermos; sin embargo, quedan todavía pacientes sin confirmación genética. Además, las mutaciones de novo no son previsibles. El diagnóstico de la NF-2 sigue siendo clínico. En los últimos años se han definido dos fenotipos de enfermedad: el leve y el moderado/grave, asociado a un inicio precoz y mutaciones de novo. También se ha constatado la alta incidencia de cataratas y de otros tumores asociados, que hasta ahora podían pasar desapercibidos: paraespinales, cutáneos y meningiomas. El inicio clínico en la edad pediátrica es más frecuente de lo esperado y muestra síntomas distintos y sutiles (AU)

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Hyperhomocysteinaemia and folate deficiency in human immunodeficiency virus-infected children.

BACKGROUND: Our aim was the detection of possible deficiencies of folate and cobalamin by the measurement of plasma total homocysteine (tHcy) in 69 human immunodeficiency virus (HIV) -infected children on antiretroviral treatment. We studied the relationship of these vitamins and methionine with tHcy values. MATERIALS AND METHODS: Plasma tHcy was determined by high-performance liquid chromatography with fluorescence detection, folate and cobalamin by competitive protein-binding chemiluminescence, and methionine by ion exchange chromatography. RESULTS: Significant differences were observed between tHcy concentrations in the HIV-infected patients and the reference values for children of similar ages (P < 0.0001). Folate values were significantly lower in HIV-infected children compared with our reference paediatric population (P < 0.0001), but cobalamin concentrations were similar between patients and reference values. A significantly negative correlation was found between tHcy and folate (r = - 0.596; P < 0.0001), and a significantly positive correlation between folate and the methionine : tHcy ratio (r = 0.501; P < 0.0001). Plasma tHcy was significantly higher (P = 0.008), while folate values and methionine : tHcy ratios were significantly lower (P = 0.007 and P = 0.042), in patients on protease inhibitor treatment than in patients on other antiretroviral therapies. CONCLUSIONS: The hyperhomocysteinaemia and low methionine : tHcy ratios observed in our group of HIV-infected children are probably a consequence of the low folate values, which interfere in the remethylation of homocysteine to methionine. Patients on protease inhibitor treatment showed significantly higher plasma tHcy concentrations, and lower folate values and methionine : tHcy ratios, compared with patients on other antiretroviral therapies. Hyperhomocysteinaemia is associated with the risk of premature stroke, which may have adverse consequences in the evolution of disease.