Growth hormone treatment does not to lead to insulin resistance nor excessive rise in IGF-1 levels, while improving height in patients small for gestational age A long-term observational study.

OBJECTIVE: In children born small for gestational age (SGA), the relationship between growth hormone (GH) treatment and insulin resistance (IR) has only been investigated for a short period, necessitating a longer observation period. This study aimed to evaluate the long-term (10 years) effect of GH to SGA-children on IR and safety during treatment. DESIGN: This was a multicenter observational study. PATIENTS: SGA-children who received GH treatment in Spain (stratified by Tanner-stage and age at GH onset [two groups: ≤6 years old or >6 years old]). MEASUREMENTS: The analysed variables (yearly measures) included auxologic, metabolic (insulin-like growth factor-1 (IGF-1), height velocity [HV], weight and homeostatic model assessment-IR [HOMA-IR]) and safety data. Data were collected prospectively (since the study approval: 2007) and retrospectively (since the initiation of GH treatment: 2005-2007). RESULTS: A total of 389 SGA children (369 Tanner-I) were recruited from 27 centres. The mean age (standard deviation) of the children at GH treatment onset was 7.2 (2.8) years old. IGF-1 (standard deviation score [SDS]) and HOMA-IR values tended to increase until the sixth year of GH-treatment, with significant differences being observed only during the first year, while these remained stable in the later years (within normal ranges). Height (SDS) increased significantly (basal: -3.0; tenth year: -1.13), and the maximum HV (SDS) occurred during the first year (2.75 ± 2.39). CONCLUSIONS: HOMA-IR values increased significantly in SGA-children during the first year of GH-treatment, remained stable and were within normal ranges in all cases. Our 10-year data suggests that long-term GH treatment does not promote IR and is well-tolerated, safe and effective.

High prevalence of variants in skeletal dysplasia associated genes in individuals with short stature and minor skeletal anomalies.

OBJECTIVE: Next generation sequencing (NGS) has expanded the diagnostic paradigm turning the focus to the growth plate. The aim of the study was to determine the prevalence of variants in genes implicated in skeletal dysplasias in probands with short stature and mild skeletal anomalies. DESIGN: Clinical and radiological data were collected from 108 probands with short stature and mild skeletal anomalies. METHODS: A customized skeletal dysplasia NGS panel was performed. Variants were classified using ACMG recommendations and Sherloc. Anthropometric measurements and skeletal anomalies were subsequently compared in those with or without an identified genetic defect. RESULTS: Heterozygous variants were identified in 21/108 probands (19.4%). Variants were most frequently identified in ACAN (n = 10) and IHH (n = 7) whilst one variant was detected in COL2A1, CREBBP, EXT1, and PTPN11. Statistically significant differences (P < 0.05) were observed for sitting height/height (SH/H) ratio, SH/H ratio standard deviation score (SDS), and the SH/H ratio SDS >1 in those with an identified variant compared to those without. CONCLUSIONS: A molecular defect was elucidated in a fifth of patients. Thus, the prevalence of mild forms of skeletal dysplasias is relatively high in individuals with short stature and mild skeletal anomalies, with variants in ACAN and IHH accounting for 81% of the cases. An elevated SH/H ratio appears to be associated with a greater probability in detecting a variant, but no other clinical or radiological feature has been found determinant to finding a genetic cause. Currently, we cannot perform extensive molecular studies in all short stature individuals so detailed clinical and radiological phenotyping may orientate which are the candidate patients to obtain worthwhile results. In addition, detailed phenotyping of probands and family members will often aid variant classification.

Adherence and long-term outcomes of growth hormone therapy with easypod™ in pediatric subjects: Spanish ECOS study.

BACKGROUND: Non-adherence to r-hGH treatments occurs in a variable percentage of subjects. One problem found when evaluating adherence is the great variability in methods of detection and definitions utilized in studies. This study assessed the level of adherence in subjects receiving r-hGH with the easypod™ electronic device. METHODS: National, multicenter, prospective and observational study involving 238 subjects (144 with GH deficiency (GHD), and 86 with small for gestational age (SGA), 8 with Turner Syndrome), who received r-hGH with easypod™ for at least 3 months before inclusion. The follow-up period was 4 years. RESULTS: Overall adherence was 94.5%; 97.5% after 6 months, 95.3% after 1 year, 93.7% after 2, 94.4% after 3 and 95.5% after 4 years of treatment. No differences in adherence were observed between prepubertal and pubertal groups and GHD and SGA groups. Change in height after 1 and 2 years, change in height SDS after 1 and 2 years, HV after 1 year, HV SDS after at 1 and 4 years, change in BMI after 1 year and change in BMI SDS at 1 and 2 years showed significant correlation with adherence. No significant differences in adherence according to IGF-I levels were found in follow-up visits or between groups. CONCLUSIONS: The easypod™ electronic device, apart from being a precise and objective measure of adherence to r-hGH treatment, allows high compliance rates to be achieved over long periods of time. Adherence significantly impacts growth outcomes associated with r-hGH treatment.

Guía de actuación en las anomalías de la diferenciación sexual (ADS) / desarrollo sexual diferente (DSD) / Management guidelines for disorders / different sex development (DSD)

Las anomalías de la diferenciación sexual (ADS) engloban un amplio espectro de discordancias entre los criterios cromosómico, gonadal y fenotípico (genital) que definen la diferenciación sexual; actualmente, se aboga por la denominación de «desarrollo sexual diferente» (DSD). Su origen es congénito; se clasifican en función de los cromosomas sexuales presentes en el cariotipo; las causas genéticas conocidas son muy diversas y heterogéneas, aunque algunos casos pueden ser secundarios a factores maternos o medioambientales. Su diagnóstico y tratamiento requieren siempre una atención médica y psicosocial multidisciplinar. El diagnóstico etiológico precisa la interacción entre las exploraciones clínicas, bioquímicas (hormonales), genéticas, de imagen y, eventualmente, quirúrgicas. El tratamiento debe abordar la asignación de género, la posible necesidad de tratamiento hormonal substitutivo (suprarrenal si hay insuficiencia suprarrenal y con esteroides sexuales si hay insuficiencia gonadal a partir de la edad puberal), la necesidad de intervenciones quirúrgicas sobre las estructuras genitales (actualmente se tiende a diferirlas) y/o sobre las gónadas (en función de los riesgos de malignización), la necesidad de apoyo psicosocial y, finalmente, una adecuada programación de la transición a la atención médica en las especialidades de adultos. Las asociaciones de personas afectadas tienen un papel fundamental en el apoyo a familias y la interacción con los medios profesionales y sociales. La utilización de Registros y la colaboración entre profesionales en Grupos de Trabajo de sociedades médicas nacionales e internacionales es fundamental para avanzar en mejorar los medios diagnósticos y terapéuticos que precisan los DSD

Disorders of Sex Development (DSD) include a wide range of anomalies among the chromosomal, gonadal, and phenotypic (genital) characteristics that define sexual differentiation. At present, a definition as Different Sexual Development (DSD) is currently preferred. They originate in the pre-natal stage, are classified according to the sex chromosomes present in the karyotype. The known genetic causes are numerous and heterogeneous, although, in some cases, they may be secondary to maternal factors and/or exposure to endocrine-disrupting chemicals (EDCs). The diagnosis and treatment of DSD always requires multidisciplinary medical and psychosocial care. An aetiological diagnosis needs the interaction of clinical, biochemical (hormonal), genetic, imaging and, sometimes, surgical examinations. The treatment should deal with sex assignment, the possible need for hormone replacement therapy (adrenal if adrenal function is impaired, and with sex steroids from pubertal age if gonadal function is impaired), as well as the need for surgery on genital structures (currently deferred when possible) and/or on gonads (depending on the risk of malignancy), the need of psychosocial support and, finally, an adequate organisation of the transition to adult medical specialties. Patient Support Groups have a fundamental role in the support of families, as well as the interaction with professional and social media. The use of Registries and the collaboration between professionals in Working Groups of national and international medical societies are crucial for improving the diagnostic and therapeutic tools required for the care of patients with DSD

[Management guidelines for disorders / different sex development (DSD)]. / Guía de actuación en las anomalías de la diferenciación sexual (ADS) / desarrollo sexual diferente (DSD).

Disorders of Sex Development (DSD) include a wide range of anomalies among the chromosomal, gonadal, and phenotypic (genital) characteristics that define sexual differentiation. At present, a definition as Different Sexual Development (DSD) is currently preferred. They originate in the pre-natal stage, are classified according to the sex chromosomes present in the karyotype. The known genetic causes are numerous and heterogeneous, although, in some cases, they may be secondary to maternal factors and/or exposure to endocrine-disrupting chemicals (EDCs). The diagnosis and treatment of DSD always requires multidisciplinary medical and psychosocial care. An aetiological diagnosis needs the interaction of clinical, biochemical (hormonal), genetic, imaging and, sometimes, surgical examinations. The treatment should deal with sex assignment, the possible need for hormone replacement therapy (adrenal if adrenal function is impaired, and with sex steroids from pubertal age if gonadal function is impaired), as well as the need for surgery on genital structures (currently deferred when possible) and/or on gonads (depending on the risk of malignancy), the need of psychosocial support and, finally, an adequate organisation of the transition to adult medical specialties. Patient Support Groups have a fundamental role in the support of families, as well as the interaction with professional and social media. The use of Registries and the collaboration between professionals in Working Groups of national and international medical societies are crucial for improving the diagnostic and therapeutic tools required for the care of patients with DSD.

Incremento de lipoproteína(a) en paciente pediátrico asociado a síndrome nefrótico / Increased lipoprotein(a) in a paediatric patient associated with nephrotic syndrome

Una complicación común en los pacientes pediátricos con síndrome nefrótico (SN) es la hiperlipidemia. Alrededor del 20% de los niños no responden al tratamiento con corticoides, presentando un SN corticorresistente (SNCR), que puede evolucionar a insuficiencia renal. Se ha observado que los pacientes pediátricos con SNCR cursan con incremento de c-LDL, c-VLDL y triglicéridos, y presentan niveles elevados de lipoproteína (a) [Lp(a)]. Presentamos el caso de un niño de 5 años con diagnóstico de SNCR y dislipemia, con niveles incrementados de c-LDL, apo B100 y Lp(a). Tras el mal pronóstico de la función renal, se inicia tratamiento inmunosupresor con tacrolimus y con atorvastatina para controlar la dislipemia. A pesar de que el tacrolimus produce una elevación del colesterol total y c-LDL, las notables alteraciones del perfil lipídico del niño sugieren la existencia de un riesgo cardiovascular elevado. En estos casos sería interesante disponer de valores de referencia en edades pediátricas para nuestra área sanitaria

A common complication in paediatric patients with nephrotic syndrome (NS) is hyperlipidaemia. About 20% of children do not respond to treatment with corticosteroids, presenting with a cortico-resistant NS (CRNS), which can progress to kidney failure. It has been observed that paediatric patients with CRNS have an elevated low density lipoprotein cholesterol (LDL-c), very low density lipoprotein cholesterol (VLDL-c), and triglycerides levels, as well as elevated Lipoprotein-a [Lp (a)] levels. The case is presented of a 5 year old boy, diagnosed with CRNS, presenting with dyslipidaemia with increased LDL-c, Apo-B100, and Lp(a) levels. After the poor prognosis of the renal function, immunosuppressant treatment was started with tacrolimus and atorvastatin to control dyslipidaemia. Although tacrolimus causes an elevation of total cholesterol and LDL-c, the significant alterations of the children lipid profile suggest the existence of a high cardiovascular risk. In these cases, it would be interesting to have reference values in children in our health area

[Increased lipoprotein(a) in a paediatric patient associated with nephrotic syndrome]. / Incremento de lipoproteína(a) en paciente pediátrico asociado a síndrome nefrótico.

A common complication in paediatric patients with nephrotic syndrome (NS) is hyperlipidaemia. About 20% of children do not respond to treatment with corticosteroids, presenting with a cortico-resistant NS (CRNS), which can progress to kidney failure. It has been observed that paediatric patients with CRNS have an elevated low density lipoprotein cholesterol (LDL-c), very low density lipoprotein cholesterol (VLDL-c), and triglycerides levels, as well as elevated Lipoprotein-a [Lp (a)] levels. The case is presented of a 5 year old boy, diagnosed with CRNS, presenting with dyslipidaemia with increased LDL-c, Apo-B100, and Lp(a) levels. After the poor prognosis of the renal function, immunosuppressant treatment was started with tacrolimus and atorvastatin to control dyslipidaemia. Although tacrolimus causes an elevation of total cholesterol and LDL-c, the significant alterations of the children lipid profile suggest the existence of a high cardiovascular risk. In these cases, it would be interesting to have reference values in children in our health area.

Human MAMLD1 Gene Variations Seem Not Sufficient to Explain a 46,XY DSD Phenotype.

MAMLD1 is thought to cause disordered sex development in 46,XY patients. But its role is controversial because some MAMLD1 variants are also detected in normal individuals, several MAMLD1 mutations have wild-type activity in functional tests, and the male Mamld1-knockout mouse has normal genitalia and reproduction. Our aim was to search for MAMLD1 variations in 108 46,XY patients with disordered sex development, and to test them functionally. We detected MAMDL1 variations and compared SNP frequencies in controls and patients. We tested MAMLD1 transcriptional activity on promoters involved in sex development and assessed the effect of MAMLD1 on androgen production. MAMLD1 expression in normal steroid-producing tissues and mutant MAMLD1 protein expression were also assessed. Nine MAMLD1 mutations (7 novel) were characterized. In vitro, most MAMLD1 variants acted similarly to wild type. Only the L210X mutation showed loss of function in all tests. We detected no effect of wild-type or MAMLD1 variants on CYP17A1 enzyme activity in our cell experiments, and Western blots revealed no significant differences for MAMLD1 protein expression. MAMLD1 was expressed in human adult testes and adrenals. In conclusion, our data support the notion that MAMLD1 sequence variations may not suffice to explain the phenotype in carriers and that MAMLD1 may also have a role in adult life.

Anomalías de la diferenciación sexual. Síndrome del varón XX / Sexual differentiation anomalies. XX male síndrome

No disponible

-LDL/ApoB-100 en niños obesos resistentes a la insulina como herramienta clínica para valorar el riesgo cardiovascular / c-LDL/ApoB-100 in insulin resistance obese children as a clinical tool for assessing cardiovascular risk / c-LDL/Apo B-100 em crianças obesas insulino-resistentes como ferramenta clínica para avaliar o risco cardiovascular

La obesidad es la enfermedad nutricional más frecuente en niños y adolescentes en los países desarrollados. Se caracteriza por un estado proinfamatorio que supone una interrupción de las señales de traducción de la insulina con la consiguiente resistencia a la insulina. El objetivo del estudio fue valorar la presencia de factores de riesgo cardiovasculares y de partículas de c-LDL pequeñas y densas mediante el cálculo del índice c-LDL/ApoB-100 en una población infantil obesa insulinorresistente. Se incluyeron niños de ambos sexos con edades comprendidas entre 2 y 12 años que acudieron a las consultas de pediatría del Hospital Universitario Virgen Macarena. Se reclutó una cohorte de 200 niños correspondiente a un total de 97 niños y 103 niñas distribuidos en los siguientes grupos: Grupo 1: n=96 con obesidad (P97) y resistencia a la insulina (RI); y Grupo 2, n=104, con peso normal (P<80). Se calculó el per-centilo del IMC para cada edad y sexo así como se analizó el perfil lipídico y bioquímico. Ambos grupos contaron con el consentimiento informado previo a la extracción de la muestra por parte de los familiares. El cociente c-LDL/ApoB-100 alcanzó mayor significación estadística y área bajo la curva (AUC) que otros cocientes valorados, con una sensibilidad (S)=87 y especificidad (E)=0,585 para el valor de 1,3 y un AUC de 0,78 y p<0,001. Además, se obtuvo una correlación negativa entre el cociente c-LDL/ApoB-100 y el HOMA (p<0,05), el fbrinógeno (p<0,05) y us-PCR (p<0,05). El cociente c-LDL/ApoB-100 podría ser un parámetro determinante de la presencia de partículas pequeñas y densas con alta sensibilidad, significación estadística y valor predictivo positivo en una población infantil obesa e insulinorresistente como herramienta clínica para valorar el riesgo cardiovascular.

Obesity is the most common( nutritional disease in children and adolescents in developed countries. It is a proinfammatory disease that implies a break in the transduction signal of insulin with subsequent insulin resistance. The aim of the study was to assess the presence of particles of small and dense c-LDL by calculating the c-LDL/ApoB-100 index in an insulin resistant obese children population. Children of both sexes aged between 2 and 12 attending the pediatric outpatient clinics of Hospital Universitario Virgen Macarena were included. It recruited a cohort of 200 children, with a total of 103 girls and 97 boys distributed in the following groups: Group 1: n=96 obese (P97) and IR and n=104 normal weight, Group 2 (P<80). BMI percentile for age and sex as well as lipid and biochemical profle were calculated. Both groups had informed consent from relatives before the extraction. The c-LDL/ApoB-100 achieved greater statistical significance and area under the curve (AUC) than other ratios measured with sensibil-ity (S)=87 and specificity (E)=0.585 for the value of 1.3 with an AUC of 0.78 and p<0.001. Besides, a negative correlation between the c-LDL/Apo-B-100 and HOMA (p<0.05), fbrinogen (p<0.05) and us-PCR (p<0.05) ratios is obtained. The LDL/ApoB-100 ratio is a determining parameter for presence of small and dense LDL particles with high sensitivity, statistical significance and positive predictive value in an insulin resistant obese children population as a clinical tool to assess cardiovascular risk.

A obesidade é a doença nutricional mais comum em crianças e adolescentes nos países desenvolvidos. Caraceriza-se por um estado pró-infamatório que supõe uma interrupção dos sinais de tradução da insulina com a conseguinte resistência à insulina. O objetivo do estudo foi avaliar a presença de fatores de risco cardiovasculares e de partículas de c-LDL pequenas e densas através do cálculodo índice c-LDL/ Apo B-100 numa população infantil resistente à insulina. Foram incluídas crianças de ambos os sexos com idade entre 2 e 12 anos, que foram às consultas de pediatria do Hospital Universitário Virgem Macarena. Foi recrutado um grupo de 200 crianças, correspondente a um total de 97 meninos e 103 meninas distribuídos nos seguintes grupos: Grupo 1: n=96 obesidade (P97) e resistência à insulina (RI) e n=104 Grupo 2 de peso normal (P<80). Calculou-se o percentil do IMC para cada idade e sexo, bem como o perfil lipídico e bioquímico. Ambos os grupos tinham o consentimento informado antes da ex-tração da amostra por parte da família. O quociente de c-LDL/ApoB-100 atinge significação estatística maior e área sob a curva que outros quocientes avaliados com uma sensibilidade (S)=87 e especificida-de (E)=0,585 para o valor de 1,3, e uma AUC de 0,78 e p<0,001. Além disso, foi obtida uma correla-ção negativa entre o quociente c-LDL/Apo-B-100 e o HOMA (p<0,05), o fbrinogênio (p<0,05) e us-PCR (p<0,05). O quociente c-LDL/ApoB-100 poderia ser um parâmetro de determinação da presença de partículas pequenas e densas com alta sensibilidade, significação estatística e valor preditivo positivo numa população infantil obesa e insulino-resistente como ferramenta clínica para avaliar o risco cardiovascular.

-LDL/ApoB-100 en niños obesos resistentes a la insulina como herramienta clínica para valorar el riesgo cardiovascular / c-LDL/ApoB-100 in insulin resistance obese children as a clinical tool for assessing cardiovascular risk / c-LDL/Apo B-100 em crianþas obesas insulino-resistentes como ferramenta clínica para avaliar o risco cardiovascular

La obesidad es la enfermedad nutricional más frecuente en niños y adolescentes en los países desarrollados. Se caracteriza por un estado proinfamatorio que supone una interrupción de las señales de traducción de la insulina con la consiguiente resistencia a la insulina. El objetivo del estudio fue valorar la presencia de factores de riesgo cardiovasculares y de partículas de c-LDL pequeñas y densas mediante el cálculo del índice c-LDL/ApoB-100 en una población infantil obesa insulinorresistente. Se incluyeron niños de ambos sexos con edades comprendidas entre 2 y 12 años que acudieron a las consultas de pediatría del Hospital Universitario Virgen Macarena. Se reclutó una cohorte de 200 niños correspondiente a un total de 97 niños y 103 niñas distribuidos en los siguientes grupos: Grupo 1: n=96 con obesidad (P97) y resistencia a la insulina (RI); y Grupo 2, n=104, con peso normal (P<80). Se calculó el per-centilo del IMC para cada edad y sexo así como se analizó el perfil lipídico y bioquímico. Ambos grupos contaron con el consentimiento informado previo a la extracción de la muestra por parte de los familiares. El cociente c-LDL/ApoB-100 alcanzó mayor significación estadística y área bajo la curva (AUC) que otros cocientes valorados, con una sensibilidad (S)=87 y especificidad (E)=0,585 para el valor de 1,3 y un AUC de 0,78 y p<0,001. Además, se obtuvo una correlación negativa entre el cociente c-LDL/ApoB-100 y el HOMA (p<0,05), el fbrinógeno (p<0,05) y us-PCR (p<0,05). El cociente c-LDL/ApoB-100 podría ser un parámetro determinante de la presencia de partículas pequeñas y densas con alta sensibilidad, significación estadística y valor predictivo positivo en una población infantil obesa e insulinorresistente como herramienta clínica para valorar el riesgo cardiovascular.(AU)

Obesity is the most common( nutritional disease in children and adolescents in developed countries. It is a proinfammatory disease that implies a break in the transduction signal of insulin with subsequent insulin resistance. The aim of the study was to assess the presence of particles of small and dense c-LDL by calculating the c-LDL/ApoB-100 index in an insulin resistant obese children population. Children of both sexes aged between 2 and 12 attending the pediatric outpatient clinics of Hospital Universitario Virgen Macarena were included. It recruited a cohort of 200 children, with a total of 103 girls and 97 boys distributed in the following groups: Group 1: n=96 obese (P97) and IR and n=104 normal weight, Group 2 (P<80). BMI percentile for age and sex as well as lipid and biochemical profle were calculated. Both groups had informed consent from relatives before the extraction. The c-LDL/ApoB-100 achieved greater statistical significance and area under the curve (AUC) than other ratios measured with sensibil-ity (S)=87 and specificity (E)=0.585 for the value of 1.3 with an AUC of 0.78 and p<0.001. Besides, a negative correlation between the c-LDL/Apo-B-100 and HOMA (p<0.05), fbrinogen (p<0.05) and us-PCR (p<0.05) ratios is obtained. The LDL/ApoB-100 ratio is a determining parameter for presence of small and dense LDL particles with high sensitivity, statistical significance and positive predictive value in an insulin resistant obese children population as a clinical tool to assess cardiovascular risk.(AU)

A obesidade é a doenþa nutricional mais comum em crianþas e adolescentes nos países desenvolvidos. Caraceriza-se por um estado pró-infamatório que sup§e uma interrupþÒo dos sinais de traduþÒo da insulina com a conseguinte resistÛncia O insulina. O objetivo do estudo foi avaliar a presenþa de fatores de risco cardiovasculares e de partículas de c-LDL pequenas e densas através do cálculodo índice c-LDL/ Apo B-100 numa populaþÒo infantil resistente O insulina. Foram incluídas crianþas de ambos os sexos com idade entre 2 e 12 anos, que foram Os consultas de pediatria do Hospital Universitário Virgem Macarena. Foi recrutado um grupo de 200 crianþas, correspondente a um total de 97 meninos e 103 meninas distribuídos nos seguintes grupos: Grupo 1: n=96 obesidade (P97) e resistÛncia O insulina (RI) e n=104 Grupo 2 de peso normal (P<80). Calculou-se o percentil do IMC para cada idade e sexo, bem como o perfil lipídico e bioquímico. Ambos os grupos tinham o consentimento informado antes da ex-traþÒo da amostra por parte da família. O quociente de c-LDL/ApoB-100 atinge significaþÒo estatística maior e área sob a curva que outros quocientes avaliados com uma sensibilidade (S)=87 e especificida-de (E)=0,585 para o valor de 1,3, e uma AUC de 0,78 e p<0,001. Além disso, foi obtida uma correla-þÒo negativa entre o quociente c-LDL/Apo-B-100 e o HOMA (p<0,05), o fbrinogÛnio (p<0,05) e us-PCR (p<0,05). O quociente c-LDL/ApoB-100 poderia ser um parÔmetro de determinaþÒo da presenþa de partículas pequenas e densas com alta sensibilidade, significaþÒo estatística e valor preditivo positivo numa populaþÒo infantil obesa e insulino-resistente como ferramenta clínica para avaliar o risco cardiovascular.(AU)

Protocolo de estudio bioquímico de hipercolesterolemia familiar en un niño de 6 años / Biochemistry study protocol of familial hypercholesterolaemia in a 6 year-old child

La hipercolesterolemia familiar (HF) es una de las enfermedades hereditarias más frecuentes, afectando a unas 10 millones de personas en todo el mundo. Se caracteriza por niveles elevados de c-LDL y por una elevada prevalencia de enfermedad cardiovascular prematura. La HF se origina por mutaciones en el gen que codifica el receptor de c-LDL. Presentamos el caso de un niño de 6 años que es remitido al laboratorio de Riesgo Cardiovascular (RCV) por sospecha de hipercolesterolemia familiar. Se le realiza una bioquímica general y un perfil de RCV, donde se observa un colesterol total y un c-LDL elevado, con el resto de los parámetros dentro de los rangos de normalidad. Se procede a la confirmación de la HF heterocigota mediante la determinación de la mutación del receptor de c-LDL (Lipochip(R)) mediante análisis genético (AU)

Familial hypercholesterolaemia (FH) is one of the most common hereditary diseases, affecting about 10 million people around the world. It is characterised by high levels of c-LDL, and a high prevalence of premature cardiovascular disease. It is caused by mutations in the gene that encodes the c-LDL receptor. We present the case of a 6 year-old child who was referred to the Cardiovascular Risk (CRV) Laboratory due to suspicion of familial hypercholesterolaemia. General biochemistry analysis and a CRV profile were performed, showing a high total cholesterol and c-LDL. As the rest of parameters were within the normal ranges, secondary causes of hypercholesterolaemia, such as hypothyroidism and diabetes, were ruled out. The presence of the FH heterozygote was confirmed by determining the mutation of the c-LDL receptor mutation by gene analysis (Lipochip (R)) (AU)

[Nutrition iodine status in pregnant women in the sanitary district Sierra de Huelva-Andévalo, South of Spain]. / Deficiencia nutricional de yodo en gestantes pertenecientes al distrito sanitario Sierra de Huelva-Andévalo, sur de España.

BACKGROUND: Iodine is an essential trace element implicated in synthesis of thyroid hormones. Iodine requirements vary throughout life. This iodine requirement is increased during pregnancy and breastfeeding. In a previous study carried out by our group in 2008, we detected an iodine-deficient area in the province of Huelva, specially in district Sierra de Huelva-Andévalo by means of neonatal TSH determinations. OBJECTIVE: To reinforce the iodine supplementation campaign and its impact on their newborns in order to assess nutrition iodine status in pregnant women using questionnaire and ioduria determination. MATERIAL AND METHODS: This study has been jointly carried out by Congenital Hypothyroidism Unit of the Clinical Biochemistry Department of the Virgen Macarena University Hospital (Seville) and the Gynecology and Clinical Analysis Unit of the Río Tinto Hospital (Huelva) during two years. We studied 313 pregnant women. All of them filled out a personal questionnaire to know the iodine nutritional status in their area. Ioduria was determinated by high-resolution liquid chromatography. Data from pregnant women and results of the studied variables were analyzed with SPSS v13.0. CONCLUSIONS: Pregnant women from the sanitary district Sierra de Huelva-Andévalo present a median for ioduria which corresponds to an insufficient iodine intake according to the WHO classification. The questionnaires suggest that this iodine deficiency is consequence of an insufficient iodine intake and a low adherence to the treatment.

Insuficiencia suprarrenal primaria como inicio de adrenoleucodistrofia en un varón de 4 años / Primary adrenal insufficiency as the form of onset of adrenoleukodystrophy in a 4-year-old boy

La adrenoleucodistrofia ligada al cromosoma X es una enfermedad metabólica hereditaria producida por acumulación de ácidos grasos saturados de cadena muy larga (VLCFA). dado que puede aparecer con insuficiencia suprarrenal primaria, es importante su estudio en los varones afectados. Varón de 4 años de edad con síndrome de hiperactividad, hiperpigmentación cutaneomucosa y deshidratación hiponatrémica e hiperpotasémica que es diagnosticado de adrenoleucodistrofia con insuficiencia suprarrenal primaria como forma de manifestación clínica. Presentaba: anticuerpos antiadrenales negativos; VLCFA en plasma, C26:0 = 1,25 μg/ml (0,18-0,48), C2/C22:04:0= 1,53 (< 1) y C26:0/C22:0= 0,04 (< 0,02); tomografía abdominal: glándulas suprarrenales de pequeño tamaño; resonancia magnética craneal y potenciales evocados: normales al diagnóstico y con signos de demielinización de sustancia blanca tras 2 años de seguimiento. Ante un niño varón con insuficiencia suprarrenal primaria, es necesario descartar causas autoinmunitarias y adrenoleucodistrofia antes del diagnóstico de enfermedad de Addison (AU)

X-linked adrenoleukodystrophy is an inherited metabolic disease caused by the accumulation of saturated very long chain fatty acids (VLCFA). Given that the form of presentation can be primary adrenal insufficiency, diagnosis in affected males is important. Patient was a 4-year-old boy with attention deficit hyperactivity disorder, cutaneous-mucosal hyperpigmentation, and dehydration with hyponatremia and hyperpotassemia was diagnosed with adrenoleukodystrophy presenting as primary adrenal insufficiency. Antiadrenal antibodies: negative. Plasma VLCFA: C26:0 = 1.25 mg/ml (0.18-0.48), C24:0/C22:0=1.53 (< 1), and C26:0/C22:0 = 0.04 (< 0.02). Abdominal computed tomography: small adrenal glands. Cranial magnetic resonance imaging and evoked potentials: normal at diagnosis and with signs of white matter demyelination after 2 years of follow-up. Testing for an autoimmune etiology and adrenoleukodystrophy is important in boys with primary adrenal insufficiency before Addison’s disease is diagnosed (AU)