Hyperinsulinism-hyperammonemia syndrome in two Peruvian children with refractory epilepsy.

OBJECTIVES: Congenital hyperinsulinism (HI) is a heterogeneous clinical disorder with great variability in its clinical phenotype, and to date, pathogenic variants in 23 genes have been recognized.  Hyperinsulinism-hyperammonemia syndrome (HI/HA) is the second most frequent cause of this disease that shows an autosomal dominant pattern and is caused by an activating mutation of the GLUD1 gene, which responds favorably to the use of diazoxide. HI/HA syndrome presents with fasting hypoglycemia; postprandial hypoglycemia, especially in those with a high protein content (leucine); and persistent mild hyperammonemia. Neurological abnormalities, in the form of epilepsy or neurodevelopmental delay, are observed in a high percentage of patients; therefore, timely diagnosis is crucial for proper management. CASE PRESENTATION: We report the clinical presentation of two Peruvian children that presented with epilepsy whose genetic analysis revealed a missense mutation in the GLUD1 gene, one within exon 11, at 22% mosaicism; and another within exon 7, as well as their response to diazoxide therapy. To the best of our knowledge, these are the first two cases of HI/HA syndrome reported in Peru. CONCLUSIONS: HI/HA syndrome went unnoticed, because hypoglycemia was missed and were considered partially controlled epilepsies. A failure to recognize hypoglycemic seizures will delay diagnosis and adequate treatment, so a proper investigation could avoid irreversible neurological damage.

Association of Central Precocious Puberty with a Rare Presentation of Schimmelpenning-Feuerstein-Mims Syndrome in a Peruvian Girl.

Schimmelpenning-Feuerstein-Mims syndrome (SFM), an epidermal nevus syndrome characterized by skin lesions, has an estimated incidence of 1 per 10 000 live births. Nevus sebaceous, the most common cutaneous lesion, and verrucous nevus, the less frequent lesion, are coupled with a wide range of extracutaneous manifestations. As part of these manifestations, rarely, central precocious puberty can arise. We report the case of a 1-year-5-month-old girl who presented to the Endocrinology and Metabolism Department with breast enlargement that began at one year of age, growth of pubic and axillary hair three months later, and vaginal bleeding that occurred five months later. During clinical examination, melanocytic nevi, with a diameter ranging from 3 to 5 mm, were noted on the face. Verrucous nevi of variable size with a tendency for coalescence following the lines of Blaschko and melanocytic nevi with a diameter ranging from 3 to 6 mm were observed on the right hemibody and on the left hemibody, respectively. Right asymmetry of the lower extremities was observed. Laboratory findings showed a significant increase in the levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) after the gonadotropin-releasing hormone (GnRH) stimulation test; additionally, imaging demonstrated advanced bone age and pubertal changes in the internal genitals. Analyses of the H-RAS, K-RAS, and N-RAS genes in the blood and in the skin were performed, and a missense mutation in exon 2 of the gene, H-RAS c37G > C (p.G13R), was detected in the latter. Treatment with triptorelin, a GnRH analog, was initiated, and it gave good clinical response. Epidermal nevus syndrome has a wide and variable systemic involvement. Thus, it is important to consider the development of precocious puberty for a prompt diagnosis and to strategize a multidisciplinary approach from the beginning.

Progresión clínica de la tiroiditis autoinmune en niños y adolescentes atendidos en el Instituto Nacional de Salud del Niño / Clinical progression of autoimmune thyroiditis in children and adolescents treated at the Instituto Nacional de Salud del Niño

La tiroiditis autoinmune es la causa más frecuente de hipotiroidismo adquirido en la edad pediátrica. El cuadro clínico al diagnóstico depende de la condición bioquímica en la que se encuentre y el seguimiento es fundamental para adoptar las medidas terapéuticas que garanticen un adecuado crecimiento y desarrollo. Objetivo. Describir la progresión clínica de la tiroiditis autoinmune en niños y adolescentes. Diseño. Estudio de serie de casos, longitudinal y retrospectivo. Lugar. Servicio de Endocrinología, Instituto Nacional de Salud del Niño, Lima, Perú (institución docente). Participantes. Niños y adolescentes con tiroiditis autoinmune. Intervenciones. Sesenta y cinco pacientes con tiroiditis autoinmune (58 mujeres y 7 varones), menores de 18 años, atendidos entre los años 2000 y 2012, tuvieron seguimiento por más de un año, con evaluaciones clínicas y bioquímicas periódicas. Se excluyó del estudio a los portadores de síndromes genéticos o diabetes mellitus tipo 1. Principales medidas de resultados. Progresión clínica de la tiroiditis autoinmune. Resultados. El bocio (78,5 por ciento) fue el signo predominante y a la vez factor de riesgo para evolucionar a hipotiroidismo establecido (adquirido) en quienes debutaron con hipotiroidismo subclínico. Al ingreso, el 48 por ciento de prepúberes presentó disfunción tiroidea frente al 26,6 por ciento de los púberes. De la población total, 46 por ciento tuvo hipotiroidismo establecido, 26 por ciento hipotiroidismo subclínico y 23 por ciento estado eutiroideo. El 27 por ciento de eutiroideos y 47 por ciento de hipotiroideos subclínicos evolucionaron a hipotiroidismo establecido. No hubo diferencia estadísticamente significativa de los puntajes Z promedio de talla o IMC al diagnóstico o durante el seguimiento. Conclusiones. Los niños y adolescentes con tiroiditis autoinmune que debutan en estado eutiroideo o hipotiroideo subclínico tienen riesgo alto de evolucionar a hipotiroidismo establecido, siendo...

Autoimmune thyroiditis is the most common cause of hypothyroidism in children. Clinical diagnosis depends on biochemical condition and monitoring is essential to adopt therapeutic measures and ensure proper growth and development. Objective. To describe the clinical progression of autoimmune thyroiditis in children and adolescents. Design. Retrospective, longitudinal series of cases study. Setting. Department of Endocrinology, Instituto Nacional de Salud del Niño, Lima, Peru (a teaching institution). Participants.Children and adolescents suffering of autoimmune thyroiditis. Interventions. Sixty-five patients-58 women and 7 men- under the age of 18 suffering of autoimmune thyroiditis and admitted between 2000-2012 were followed with clinical and biochemical evaluations over one year; carriers of genetic syndromes or with type 1 diabetes mellitus were excluded. Main outcome measures. Clinical progression of autoimmune thyroiditis. Results. Goiter (78.5 per cent) was a predominant sign and risk factor for development of acquired hypothyroidism in those who debuted with subclinical hypothyroidism. At admission 48 per cent of prepubescent infants presented thyroid dysfunction compared with 26.6 per cent of pubescent subjects. Out of the total population 46 per cent suffered of acquired hypothyroidism, 26 per cent subclinical hypothyroidism, and 23 per cent were euthyroid; 27 per cent of euthyroid patients and 47 per cent of subjects with subclinical hypothyroidism evolved into acquired hypothyroidism. There was no statistically significant difference in the mean Z score for height or BMI at diagnosis nor during follow-up. Conclusions. Children and adolescents with autoimmune thyroiditis debuting as euthyroid or with subclinical hypothyroidism had a high risk of developing acquired hypothyroidism. It seems important to monitor thyroid function for timely initiation of hormone replacement therapy...

Respuesta al tratamiento de la Enfermedad de Graves-Basedow en pacientes pediátricos / Response to Graves-Basedow Disease treatment in pediatric patients

Objetivos: Describir la respuesta clínica y bioquímica al tratamiento del hipertiroidismo por enfermedad de Graves en pacientes pediátricos. Diseño: Estudio retrospectivo. Institución: Instituto Nacional de Salud del Niño, Lima, Perú. Participantes: Niños con enfermedad de Graves. Métodos: Se incluyó 32 pacientes con diagnóstico de hipertiroidismo por Enfermedad de Graves, entre 1996 a 2007. Se consideró remisión, cuando se encontraban asintomáticos y bioquímicamente eutiroideos, luego de 6 meses de suspendido el tratamiento; y recaída, si luego de este periodo de tiempo, se encontró valores hormonales alterados. Principales medidas de resultados: Remisión o recaída luego del tratamiento. Resultados: Al diagnóstico, la edad promedio fue 10,5 años (3,2 a 17,9 años); 26 pacientes (81,2 por ciento) fueron de sexo femenino, 13 (40,6 por ciento) púberes y 19 (59,3 por ciento) pre-púberes. Los síntomas y signos más frecuentes fueron bocio, sudoración, nerviosismo, pérdida de peso, taquicardia y exoftalmos. Se usó metimazol como primera opción terapéutica a una dosis inicial promedio de 0,78 mg/kg/ día (0,4 a 2 mg/kg/día). La TSH (57,1 por ciento) y el T4L (50 por ciento) alcanzaron valores normales entre los 6 y 8 meses. Se observó remisión en 11 pacientes (34,3 por ciento), 3 (9,3 por ciento) sufrieron recaída, 12 (37,5 por ciento) pasaron a tratamiento con radioyodo (I131) y 6 (18,7 por ciento) continuaron recibiendo metimazol. La remisión de la enfermedad se alcanzó a los 2,81±0,91 años de tratamiento (rango de 1.5 a 4,8); 4,1 por ciento remitió luego del primer año, y 35,3 por ciento, 37,5 por ciento y 25 por ciento luego del segundo, tercer y cuarto año de tratamiento, respectivamente. La edad promedio de los que recibieron I131 fue 14,6 años (7,1 a 19,6 años), a una dosis alrededor de 7mCi. El 75 por ciento de ellos remitió a los 0,64± 0,60 años (rango de 0,16 a 1,5 años). Conclusiones: El hipertiroidismo por enfermedad de Graves es de relativa frecuencia en...

Objectives: To describe the clinical and biochemical response to treatment of hyperthyroidism. Design: Retrospective study. Setting: Instituto Nacional de Salud del Niño, Lima, Peru. Participants: Children. Methods: From 1996 to 2007 32 patients with diagnosis of hyperthyroidism were studied. Remission was defined when patients were asymptomatic and biochemically euthyroid 6 months after the end of treatment; relapse when altered hormone levels were found after this period of time. Main outcome measures: Remission or relapse following treatment. Results: Mean age at diagnosis was 10.5 years (3.2-17.9 years), 26 patients (81.2 per cent) were female; 13 (40.6 per cent) were pubertal and 19 (59.3 per cent) prepubertal. The most frequent symptoms and signs were: goiter, sweating, nervousness, weight loss, tachycardia and exophthalmos. Methimazole was used as first therapeutic option. Initial dose was 0.78mg/kg/day (0.41-2mg/kg/day) average. TSH (57.1 per cent) and FT4 (50 per cent) reached normal values between 6 and 8 months. Remission was observed in 11 patients (34.3 per cent), 3 (9.3 per cent) relapsed, 12 (37.5 per cent) then received treatment with radioiodine (I-131) and 6 (18.7 per cent) continued receiving methimazole. Remission was achieved after 2.81 ± 0.91 years of treatment (range 1.5-4.8), 4.1 per cent after the first year, and 35.3 per cent, 37.5 per cent and 25 per cent respectively after the second, third and fourth year of treatment. Average age of those receiving I-131 was 14.6 years (7.1-19.6 years), at a dose about 7mCi; 75 per cent of them showed remission after 0.64 ± 0.60 year (range 0.16-1.5 years). Conclusions: Hyperthyroidism due to Graves disease is relatively common in children. Remission was obtained in 34.3 per cent of patients treated with methimazole in 2.81 ± 0.91 years average and remission was achieved in 75 per cent of patients treated with I131, in 0.64 +/- 0.60 years average...

Características clínicas y bioquímicas de la diabetes mellitus tipo 2 (DMt2) en el Instituto Nacional de Salud del Niño / Clinical and biochemical characteristics of type 2 diabetes mellitus (DMt2) at Instituto Nacional de Salud del Niño

Objetivo: Evaluar las características clínicas y bioquímicas al momento del diagnóstico de diabetes mellitus tipo 2 (DMt2), en pacientes pediátricos. Diseño: Estudio clínico retrospectivo. Institución: Servicio de Endocrinología, Instituto Nacional de Salud del Niño, Lima, Perú. Pacientes: Niños con diabetes mellitus tipo 2. Métodos: Se revisó las historias clínicas de 187 pacientes con diabetes mellitus y se identificó 17 (9,2 por ciento) con diabetes mellitus tipo 2. Se preparó una ficha para la recolección de datos, en la cual se consignó características personales y familiares, síntomas y signos y datos bioquímicos. Principales medidas de resultados: Características clínicas y bioquímicas de los niños. Resultados: La edad promedio al momento del diagnóstico fue de 12,8 ± 3 años; 11 fueron de sexo masculino (64,7 por ciento) y 6 de sexo femenino (35,3 por ciento). Todos nacieron a término, de los cuales 17,6 por ciento fueron macrosómicos. Se encontró que 82,4 por ciento tenía antecedente familiar de diabetes tipo 2. Los síntomas más frecuentes fueron: poliuria, polidipsia, polifagia y pérdida de peso; 35,3 por ciento presentó sobrepeso, 41,2 por ciento obesidad y 65 por ciento del conjunto, acantosis nigricans. Cinco pacientes desarrollaron cetoacidosis. Se encontró que 60 por ciento tenía alteración de alguno de los componentes del perfil lipídico, siendo la más frecuente la alteración de los LDL (46,5 por ciento). Los anticuerpos anti-insulina, anti-GAD y anti-ICA fueron negativos en 85,7 por ciento; 14,3 por ciento de los pacientes mostró alguno de ellos positivos. Conclusiones: La mayor parte de los niños con DMt2 estudiados presentó antecedentes familiares de diabetes tipo 2, 75 por ciento de ellos con signos y síntomas clásicos de esta patología, acompañados de presencia de sobrepeso u obesidad y dislipidemia.

Objective: To determine clinical and biochemical characteristics in type 2 diabetes mellitus (T2DM) in pediatric patients at time of diagnosis. Design: Clinical retrospective study. Setting: Endocrinology Service, Instituto Nacional de Salud del Niño, Lima, Peru. Patients: Children with diabetes mellitus type 2. Methods: Medical records of 187 registered patients with diabetes mellitus were reviewed and 17 (9 per cent) with T2DM were identified. Personal and familiar characteristics, symptoms and biochemical data were obtained. Main outcome measures: Clinical and biochemical characteristics of pediatric patients. Results: Average age at diagnosis was 12.8±3 years, 11 were male (64.7 per cent) and 6 female (35.3 per cent). All were born at term and 17.6 per cent were macrosomic. Fourteen patients (82.4 per cent) had a family history of T2DM. Most frequent symptoms were polyuria, polydipsia, polyphagia and weight loss; 35.3 per cent were overweight, 41.2 per cent obese and 65 per cent showed acanthosis nigricans. Five patients developed ketoacidosis. Some component of the lipid profile was abnormal in 60 per cent with elevation of low-density lipoprotein cholesterol in 46.5 per cent. Anti-insulin antibodies, anti-GAD and islet cell antibodies (anti-ICA) were negative in 85.7 per cent and any of them positive in 14.3 per cent. Conclusions: In this series of children with type 2 diabetes most had a family history of type 2 diabetes, 75 per cent showed classical signs and symptoms of the disorder accompanied by overweight or obesity and dyslipidemia.