Fenotipos inesperados en el síndrome de Alport: la necesidad del estudio genético / Unexpected phenotypes in Alport syndrome: the need for genetic testing

El diagnóstico del síndrome de Alport supone un reto en la edadpediátrica, debido a la ausencia de fenotipos clínicos esperados de la enfermedad, su clásica caracterización de entidad rara y la práctica muy restringida de biopsias renales con análisis rutinario de la muestra por microscopía electrónica durante la infancia. Se presentan las características clínicas y genéticas de 6 pacientes pediátricos (4 mujeres) diagnosticados de síndromede Alport en dos centros hospitalarios entre 2018 y 2021. Todos los pacientes presentaron un debut clínico claramente diferente y ninguno presentó complicaciones auditivas nioftalmológicas. La mitad carecía de antecedentes familiares de enfermedad renal crónica. Ninguna biopsia renal realizada confirmó el diagnóstico. Todos los pacientes fueron confirmadosgenéticamente y fueron el caso índice del estudio familiar. Esta serie ilustra la presencia de fenotipos clínicos inesperados en el síndrome de Alport y refleja la necesidad de incorporar el estudio genético para su diagnóstico.

The diagnosis of Alport syndrome is a challenge in the pediatric age, due to the absence of expected clinical phenotypes of the disease, its classic characterization of a rare disease and the very restricted practice of renal biopsies with routine analysis of the sample by electron microscopy during infancy. The clinical and genetic characteristics of 6 pediatric patients (4 women) diagnosed with Alport syndrome in two hospital centers between 2018 and 2021 are reported. All patients presented a clearly different clinical debut and none presented auditory or ophthalmological complications. Half had no family history of chronic kidney disease. No kidney biopsy performed confirmed the diagnosis. All patients were genetically confirmed and were the index case in the family study. This series illustrates the presence of unexpected clinical phenotypes in Alport syndrome and reflects the need for the incorporation of the genetic study for its diagnosis.

[Unexpected phenotypes in Alport syndrome: the need for genetic testing]. / Fenotipos inesperados en el síndrome de Alport: la necesidad del estudio genético.

The diagnosis of Alport syndrome is a challenge in the pediatric age, due to the absence of expected clinical phenotypes of the disease, its classic characterization of a rare disease and the very restricted practice of renal biopsies with routine analysis of the sample by electron microscopy during infancy. The clinical and genetic characteristics of 6 pediatric patients (4 women) diagnosed with Alport syndrome in two hospital centers between 2018 and 2021 are reported. All patients presented a clearly different clinical debut and none presented auditory or ophthalmological complications. Half had no family history of chronic kidney disease. No kidney biopsy performed confirmed the diagnosis. All patients were genetically confirmed and were the index case in the family study. This series illustrates the presence of unexpected clinical phenotypes in Alport syndrome and reflects the need for the incorporation of the genetic study for its diagnosis.

El diagnóstico del síndrome de Alport supone un reto en la edad pediátrica, debido a la ausencia de fenotipos clínicos esperados de la enfermedad, su clásica caracterización de entidad rara y la práctica muy restringida de biopsias renales con análisis rutinario de la muestra por microscopía electrónica durante la infancia. Se presentan las características clínicas y genéticas de 6 pacientes pediátricos (4 mujeres) diagnosticados de síndrome de Alport en dos centros hospitalarios entre 2018 y 2021. Todos los pacientes presentaron un debut clínico claramente diferente y ninguno presentó complicaciones auditivas ni oftalmológicas. La mitad carecía de antecedentes familiares de enfermedad renal crónica. Ninguna biopsia renal realizada confirmó el diagnóstico. Todos los pacientes fueron confirmados genéticamente y fueron el caso índice del estudio familiar. Esta serie ilustra la presencia de fenotipos clínicos inesperados en el síndrome de Alport y refleja la necesidad de incorporar el estudio genético para su diagnóstico.

Evaluation of urinary acidification in children: Clinical utility.

The kidney plays a fundamental role in acid-base homeostasis by reabsorbing the filtered bicarbonate and by generating new bicarbonate, to replace that consumed in the buffering of non-volatile acids, a process that leads to the acidification of urine and the excretion of ammonium (NH4 +). Therefore, urine pH (UpH) and urinary NH4 + (UNH4 +) are valuable parameters to assess urinary acidification. The adaptation of automated plasma NH4 + quantification methods to measure UNH4 + has proven to be an accurate and feasible technique, with diverse potential indications in clinical practice. Recently, reference values for spot urine NH4 +/creatinine ratio in children have been published. UpH and UNH4 +, aside from their classical application in the study of metabolic acidosis, have shown to be useful in the identification of incomplete distal renal tubular acidosis (dRTA), an acidification disorder, without overt metabolic acidosis, extensively described in adults, and barely known in children, in whom it has been found to be associated to hypocitraturia, congenital kidney abnormalities and growth impairment. In addition, a low UNH4 + in chronic kidney disease (CKD) is a risk factor for glomerular filtration decay and mortality in adults, even in the absence of overt metabolic acidosis. We here emphasize on the need of measuring UpH and UNH4 + in pediatric population, establishing reference values, as well as exploring their application in metabolic acidosis, CKD and disorders associated with incomplete dRTA, including growth retardation of unknown cause.

Protocolo genético en Atención Primaria para enfermedades raras: el síndrome de Wolfram como prototipo / Genetic protocol in primary care for rare diseases: Wolfram syndrome as a prototype

Las enfermedades raras, pese a su baja frecuencia individual, afectan globalmente al 7% de la población, por lo que el profesional de Atención Primaria (AP) tendrá varios de estos pacientes bajo seguimiento. El 80% de estas enfermedades tienen base genética, lo que hace fundamental un asesoramiento genético adecuado. El seguimiento de pacientes con síndrome de Wolfram (SW) puede servir para diseñar un protocolo susceptible de ser utilizado en el diagnóstico y manejo de otras entidades y ser utilizado por profesionales sanitarios para dar soporte a los pacientes, contando con la participación de profesionales sanitarios e investigadores especializados en el SW, los propios pacientes y su entorno. Se desarrollan los pasos fundamentales de todo procedimiento clínico genético, en el que la AP es clave para dar soporte a estas familias y transmitir de forma comprensible la información sobre los aspectos genéticos.(AU)

Rare diseases, despite their individual low frequency, affect 7% of the population all combined. Consequently, every primary care practitioner (PCP) will have several of these patients under his care. 80% of rare diseases are genetically determined, which makes genetic counseling fundamental in these cases. The follow-up of patients with Wolfram syndrome (WS) can be used to design a protocol to support these patients, with the participation of researchers and healthcare professionals specialized in WS, the patients themselves and their familial environment. This protocol can be suitable for the diagnosis and management of other diseases as well. The main steps of every genetic clinical procedure are developed in this article, emphasizing the role of PCP in supporting patients and their families and in transmitting genetic information in a comprehensible manner.(AU)

[Genetic protocol in primary care for rare diseases: Wolfram syndrome as a prototype]. / Protocolo genético en Atención Primaria para enfermedades raras: el síndrome de Wolfram como prototipo.

Rare diseases, despite their individual low frequency, affect 7% of the population all combined. Consequently, every primary care practitioner (PCP) will have several of these patients under his care. 80% of rare diseases are genetically determined, which makes genetic counseling fundamental in these cases. The follow-up of patients with Wolfram syndrome (WS) can be used to design a protocol to support these patients, with the participation of researchers and healthcare professionals specialized in WS, the patients themselves and their familial environment. This protocol can be suitable for the diagnosis and management of other diseases as well. The main steps of every genetic clinical procedure are developed in this article, emphasizing the role of PCP in supporting patients and their families and in transmitting genetic information in a comprehensible manner.

Hipertensión arterial en el lactante. Un reto diagnóstico en pediatría / Infantile arterial hypertension: A diagnostic challenge in paediatrics

La prevalencia de la hipertensión arterial ha aumentado considerablemente en la edad pediátrica como consecuencia principal de su detección en niños mayores y adolescentes, en quienes predomina la causa esencial (primaria). En otras etapas de la edad pediátrica la HTA es menos frecuente, en especial en lactantes. En este grupo la hipertensión arterial obedece casi siempre a causas secundarias, en ocasiones potencialmente graves, por lo que resulta imprescindible detectarla, llevar a cabo un proceso diagnóstico etiológico adecuado y proporcionar al paciente un adecuado tratamiento, que suele requerir de un profesional especializado. A las dificultades técnicas propias de la medición de la presión arterial en los lactantes se añade la ausencia de recomendaciones específicas relacionadas con su identificación sistemática y de valores de normalidad bien establecidos en este rango de edad, por lo que su manejo constituye un reto diagnóstico y terapéutico para el profesional. A través de la exposición de 3 casos de hipertensión detectada en la etapa de lactante, se pretende sensibilizar al pediatra sobre esta enfermedad, así como proporcionar información sobre su orientación diagnóstica y terapéutica, incidiendo asimismo en las medidas farmacológicas

Arterial Hypertension prevalence (HTN) has significantly increased in paediatric patients, mainly in older children and teenagers. In these subjects the most common type is essential or primary HTN. However, in infants HTN prevalence is significantly lower and is almost always due to secondary causes, which can be potentially severe. Hence the importance of its detection, in order to establish an etiological diagnosis and provide an appropriate treatment, which usually requires a specialist physician. In addition to the technical difficulties of blood pressure measurement in infants, the lack of recommendations to perform a systematic screening in this age range and the absence of well-established normal values turns infancy-onset HTN into a diagnostic and therapeutic challenge for the physician. By means of the exposition of three infancy-onset HTN cases, the aim is to increase the paediatrician's awareness of this pathology and also to provide information about its diagnostic and therapeutic approach, dealing also with pharmacological measures of treatment

Bone Disease in CKD in Children.

This manuscript discusses mineral and bone disorders of chronic kidney disease (MBD-CKD) in pediatric patients with special emphasis on the underlying pathophysiology, the causes and clinical profile of growth retardation, the alterations in the growth plate, the strategies to optimize growth and the medical recommendations for prevention and treatment.

[Infantile arterial hypertension: A diagnostic challenge in paediatrics]. / Hipertensión arterial en el lactante. Un reto diagnóstico en pediatría.

Arterial Hypertension prevalence (HTN) has significantly increased in paediatric patients, mainly in older children and teenagers. In these subjects the most common type is essential or primary HTN. However, in infants HTN prevalence is significantly lower and is almost always due to secondary causes, which can be potentially severe. Hence the importance of its detection, in order to establish an etiological diagnosis and provide an appropriate treatment, which usually requires a specialist physician. In addition to the technical difficulties of blood pressure measurement in infants, the lack of recommendations to perform a systematic screening in this age range and the absence of well-established normal values turns infancy-onset HTN into a diagnostic and therapeutic challenge for the physician. By means of the exposition of three infancy-onset HTN cases, the aim is to increase the paediatrician's awareness of this pathology and also to provide information about its diagnostic and therapeutic approach, dealing also with pharmacological measures of treatment.