[Contiguous gene deletion syndrome in Xp21: the association between glycerol kinase deficiency, congenital suprarenal hypoplasia and Duchenne's muscular dystrophy]. / Sindrome de deleción de genes contiguos en Xp21: asociación de deficiencia de glicerolcinasa, hipoplasia suprarrenal congénita y distrofia muscular de Duchenne.

INTRODUCTION: Complex glycerol kinase (GK) deficiency is a contiguous deletion of genes in Xp21 with loss of the locus for GK, for congenital adrenal hypoplasia (AHC) and/or for Duchenne's muscular dystrophy (DMD). We report the case of a 7-year-old patient with this rare disease. CASE REPORT: Our patient was a full-term male, with normal gestation and delivery, and no relevant family history. At the age of 11 days he presented a clinical picture of salt loss with lethargy, vomiting, metabolic acidosis, hypoglycaemia, hyponatraemia and hyperpotassaemia. Fluid therapy and treatment with corticoids was established. The patient's condition developed with moderate mental retardation and progressive muscular weakness. In the physical examination, the skull and face were seen to be 'hourglass' shaped. Decompensations associated to infectious processes and fasting hypoglycaemia, hydroelectrolytic disorders and ketoacidosis are all frequent. Lab findings showed a drop in cortisol levels, elevation of muscle enzymes, 'pseudohypertriglyceridaemia' and raised levels of glycerol in plasma and urine. Karyotype and neuroimaging tests were normal. A myopathic pattern was observed in the electromyogram. The genetic study confirmed the deletion in Xp21 of the genes responsible for DMD, the GK deficit and AHC. CONCLUSIONS: Early identification of this disease makes it possible to foresee the acute metabolic decompensations and to establish suitable genetic counselling. CK and triglyceride counts should be performed in all male patients that present a suprarenal hypoplasia; if levels are high, then it is necessary to confirm the raised glycerol values and to carry out a confirmatory genetic study.

Síndrome de deleción de genes contiguos en Xp21: asociación de deficiencia de glicerolcinasa, hipoplasia suprarrenal congénita y distrofia muscular de Duchenne / contiguous gene deletion syndrome in Xp21: the association between glycerol kinase deficiency, congenital suprarrenal hypoplasia and Duchenne´s muscular dystrophy

Introducción. El déficit complejo de glicerocinasa (GK) corresponde a una deleción contigua de genes en Xp21 con pérdida del locus de la GK, de la hipoplasia adrenal congénita (AHC) y/o de la distrofia muscular de Duchenne (DMD). Presentamos un paciente de 7 años con esta rara enfermedad. Caso clínico. Varón nacido a término, con gestación y parto normales, sin antecedentes familiares de interés. Presentó a los 11 días de vida un cuadro de pérdida salina con letargia, vómitos, acidosis metabólica, hipoglucemia, hiponatremia e hiperpotasemia. Se instauró un tratamiento con fluidoterapia y corticoides. Evolucionó con un retraso mental moderado y una debilidad muscular progresiva. En la exploración se objetivó un aspecto craneofacial ‘en reloj de arena’. Son frecuentes las descompensaciones asociadas a procesos infecciosos y ayuno con hipoglucemia, alteraciones hidroelectrolíticas y cetoacidosis. En la analítica destacó el descenso de cortisol, la elevación de enzimas musculares, una ‘pseudohipertrigliceridemia’ y la elevación de glicerol en plasma y orina. El cariotipo y la neuroimagen fueron normales. En el electromiograma se observó un patrón miopático. El estudio genético confirmó la deleción en Xp21 de los genes responsables de la DMD, el déficit de GK y la AHC. Conclusiones. La identificación precoz de esta enfermedad permite prever las descompensaciones metabólicas agudas y establecer un consejo genético adecuado. En todo paciente varón que presente una hipoplasia suprarrenal, se debe realizar una determinación de creatincinasa y triglicéridos, y en el caso de estar aumentados, confirmar la elevación de glicerol y realizar el estudio genético confirmatorio

Introduction. Complex glycerol kinase (GK) deficiency is a contiguous deletion of genes in Xp21 with loss of the locus for GK, for congenital adrenal hypoplasia (AHC) and/or for Duchenne’s muscular dystrophy (DMD). We report the case of a 7-year-old patient with this rare disease. Case report. Our patient was a full-term male, with normal gestation and delivery, and no relevant family history. At the age of 11 days he presented a clinical picture of salt loss with lethargy, vomiting, metabolic acidosis, hypoglycaemia, hyponatraemia and hyperpotassaemia. Fluid therapy and corticoids treatment was established. The patient’s condition developed with moderate mental retardation and progressive muscular weakness. In the physical examination, the skull and face were seen to be ‘hourglass’ shaped. Decompensations associated to infectious processes and fasting hypoglycaemia, hydroelectrolytic disorders and ketoacidosis are all frequent. Lab findings showed a drop in cortisol levels, elevation of muscle enzymes, ‘pseudohypertriglyceridaemia’ and raised levels of glycerol in plasma and urine. Karyotype and neuroimaging tests were normal. A myopathic pattern was observed in the electromyogram. The genetic study confirmed the deletion in Xp21 of the genes responsible for DMD, the GK deficit and AHC. Conclusions. Early identification of this disease makes it possible to foresee the acute metabolic decompensations and to establish suitable genetic counselling. creatin kinase and triglyceride counts should be performed in all male patients that present a suprarenal hypoplasia; if levels are high, then it is necessary to confirm the raised glycerol values and to carry out a confirmatory genetic study

[Myoadenylate deaminase deficiency in a child with myalgias induced by physical exercise]. / Déficit de mioadenilato desaminasa en un niño con mialgias relacionadas con la actividad física.

INTRODUCTION: Myoadenylate deaminase deficiency (MAD) constitutes the most common genetically determined enzymatic defect of the skeletal muscle (2% of the population), however, it causes clinical symptoms such us exercise-related muscle cramps and pain in quite a lower number of patients, being exceptional in children. CASE REPORT: A 7 year old boy is referred with intense myalgias after physical exertion associating increased creatin kinase level 3,273 UI/L (normal 24-195) which goes down in rest period to increase again with myalgias during exercise. The ischemic forearm exercise test shows a flat ammonia curve with a normal lactate rise in relation to control. In muscle biopsy, an absence of the enzymatic activity of myoadenylate deaminase is observed and the genetic analysis proves the 'nonsense' Q12X mutation which he has in a homozygous status. CONCLUSION: MAD deficiency must be ruled out in every patient with exertional myalgia and increased CK which normalizes when asymptomatic. The ischemic forearm exercise test guides about the muscle metabolic disorder type, although the definitive diagnosis is obtained through the muscle biopsy histoenzymatic analysis and genetic techniques. Although rarely diagnosed in children, MAD deficiency must be included in the differential diagnosis of syndromes with exercise intolerance