[McArdle's disease in four pediatric patients. Diagnostic algorithm for exercise intolerance]. / Enfermedad de McArdle en cuatro pacientes pediátricos. Algoritmo diagnóstico ante una intolerancia al ejercicio.

INTRODUCTION: McArdle's disease is caused by a mutation in the PYGM gene, causing a muscle myophosphorylase deficiency, altering the release of glucose-1-P from glycogen. It usually manifests itself in childhood with early and excessive tiredness, myalgias, cramps and contractures or rhabdomyolysis, although it is not usually diagnosed until adulthood. Creatine kinase increases sharply during exercise. Four pediatric patients are presented, the pathophysiology is summarized, and a diagnostic algorithm is proposed. PATIENTS AND METHODS: Ages between 6 and 14 years, the anamnesis, physical examination, biochemistry, elec-tro-myogram, ischemia test and genetic study are described. Muscle biopsy in a single patient. The algorithm was developed from the ischemia test. RESULTS: In the three men, myalgias appeared after finishing each sports session. Phenomenon 'second wind' in one case. Ischemia test without lactate elevation and marked ammonia elevation in all. Only one muscle biopsy with glycogen deposits and absence of myophosphorylase. PYGM gene with homozygous mutations in all. Dietary treatment attenuated their symptoms during aerobic exercises. CONCLUSIONS: The ischemia test was very useful to demonstrate a dysfunction in anaerobic glycolysis. It is worth noting that oral glucose supplementation is very useful in McArdle disease, but is contraindicated in all six defects of anaerobic glycolysis. The algorithm also allows targeting the defect of 20 metabolic or structural myopathies, which are summarized.

TITLE: Enfermedad de McArdle en cuatro pacientes pediátricos. Algoritmo diagnóstico ante una intolerancia al ejercicio.Introducción. La enfermedad de McArdle está causada por una mutación en el gen PYGM y déficit de miofosforilasa muscular, resultando alterada la liberación de glucosa-1-P a partir del glucógeno. Suele manifestarse en la infancia con cansancio precoz y excesivo, mialgias, calambres y contracturas o rabdomiólisis, aunque no suele diagnosticarse hasta la etapa adulta. La creatincinasa se incrementa durante el ejercicio. Se presentan cuatro pacientes pediátricos, se resume la fisiopatología y se propone un algoritmo diagnóstico. Pacientes y métodos. Pacientes con edades entre 6 y 14 años. Se describe la anamnesis, la exploración física, la bioquímica, el electromiograma, el test de isquemia y el estudio genético, con biopsia muscular a un solo paciente. Se elabora un algoritmo a partir del test de isquemia. Resultados. En los tres varones, las mialgias aparecieron tras finalizar cada sesión deportiva, con un fenómeno second wind en un caso. Se apreció un test de isquemia sin elevación del lactato y marcada elevación del amonio en todos, una biopsia muscular con depósitos de glucógeno y ausencia de miofosforilasa, y gen PYGM con mutaciones homocigotas en todos. El tratamiento dietético les atenuó la sintomatología durante los ejercicios aeróbicos. Conclusiones. El test de isquemia resultó muy útil para demostrar una disfunción en la glucólisis anaeróbica. Se destaca que el suplemento oral de glucosa es muy útil para la enfermedad de McArdle, pero está contraindicado en los seis defectos de la glucólisis anaeróbica. El algoritmo también permite orientar el defecto de 20 miopatías metabólicas o estructurales, que se resumen.

Enfermedad de McArdle en cuatro pacientes pediátricos. Algoritmo diagnóstico ante una intolerancia al ejercicio / McArdle’s disease in four pediatric patients. Diagnostic algorithm for exercise intolerance

Introducción: La enfermedad de McArdle está causada por una mutación en el gen PYGM y déficit de miofosforilasa muscular, resultando alterada la liberación de glucosa-1-P a partir del glucógeno. Suele manifestarse en la infancia con cansancio precoz y excesivo, mialgias, calambres y contracturas o rabdomiólisis, aunque no suele diagnosticarse hasta la etapa adulta. La creatincinasa se incrementa durante el ejercicio. Se presentan cuatro pacientes pediátricos, se resume la fisiopatología y se propone un algoritmo diagnóstico. Pacientes y métodos: Pacientes con edades entre 6 y 14 años. Se describe la anamnesis, la exploración física, la bioquímica, el electromiograma, el test de isquemia y el estudio genético, con biopsia muscular a un solo paciente. Se elabora un algoritmo a partir del test de isquemia. Resultados: En los tres varones, las mialgias aparecieron tras finalizar cada sesión deportiva, con un fenómeno second wind en un caso. Se apreció un test de isquemia sin elevación del lactato y marcada elevación del amonio en todos, una biopsia muscular con depósitos de glucógeno y ausencia de miofosforilasa, y gen PYGM con mutaciones homocigotas en todos. El tratamiento dietético les atenuó la sintomatología durante los ejercicios aeróbicos. Conclusiones: El test de isquemia resultó muy útil para demostrar una disfunción en la glucólisis anaeróbica. Se destaca que el suplemento oral de glucosa es muy útil para la enfermedad de McArdle, pero está contraindicado en los seis defectos de la glucólisis anaeróbica. El algoritmo también permite orientar el defecto de 20 miopatías metabólicas o estructurales, que se resumen.(AU)

INTRODUCTION: McArdle’s disease is caused by a mutation in the PYGM gene, causing a muscle myophosphorylase deficiency, altering the release of glucose-1-P from glycogen. It usually manifests itself in childhood with early and excessive tiredness, myalgias, cramps and contractures or rhabdomyolysis, although it is not usually diagnosed until adulthood. Creatine kinase increases sharply during exercise. Four pediatric patients are presented, the pathophysiology is summarized, and a diagnostic algorithm is proposed. PATIENTS AND METHODS: Ages between 6 and 14 years, the anamnesis, physical examination, biochemistry, elec­tro­myogram, ischemia test and genetic study are described. Muscle biopsy in a single patient. The algorithm was developed from the ischemia test. RESULTS: In the three men, myalgias appeared after finishing each sports session. Phenomenon ‘second wind’ in one case. Ischemia test without lactate elevation and marked ammonia elevation in all. Only one muscle biopsy with glycogen deposits and absence of myophosphorylase. PYGM gene with homozygous mutations in all. Dietary treatment attenuated their symptoms during aerobic exercises. CONCLUSIONS:The ischemia test was very useful to demonstrate a dysfunction in anaerobic glycolysis. It is worth noting that oral glucose supplementation is very useful in McArdle disease, but is contraindicated in all six defects of anaerobic glycolysis. The algorithm also allows targeting the defect of 20 metabolic or structural myopathies, which are summarized.(AU)

Enfermedad respiratoria y parálisis diafragmática en la enfermedad de Charcot-Marie-Tooth / Respiratory disease and diaphragm paralysis in Charcot-Marie-Tooth disease

La disfunción diafragmática bilateral es una entidad infrecuente. Dentro del ámbito pediátrico las causas más comunes son las asociadas a traumatismo obstétrico o cirugía cardiovascular. En el diagnóstico diferencial se incluye la enfermedad de Charcot-Marie-Tooth (CMT).Si bien en esta enfermedad es infrecuente, la afectación de la musculatura respiratoria, por su carácter distal, está descrita su asociación con neumopatía restrictiva secundaria a una disfunción del nervio frénico con paresia diafragmática bilateral o anomalías de la pared torácica. Presentamos 2 casos de CMT que ingresaron en la Unidad de Cuidados Intensivos con fallo respiratorio tipo II. En ambos casos el tratamiento con ventilación no invasiva produjo una mejoría clínica significativa. A destacar el hecho de que en uno de los pacientes la evidencia de una afectación frénica sirvió como signo guía para el diagnóstico de su enfermedad de base (AU)

Diaphragmatic bilateral palsy is uncommon in children. The most important etiologies are thoracic surgery and obstetric trauma. Respiratory muscle impairment is a rare phenomenon in patients with Charcot-Marie-Tooth disease (CMT). However, it can be associated with restrictive pulmonary impairment, phrenic nerve dysfunction or thoracic cage abnormalities. We report two paediatric cases of CMT disease with type 2 respiratory failure due to diaphragmatic dysfunction. In both cases treatment with non-invasive mechanical ventilation resulted in satisfactory clinical improvement. Evidence of phrenic damage was the main clue in one patient in order to obtain an accurate diagnostic of her disease (AU)

[Respiratory disease and diaphragm paralysis in Charcot-Marie-Tooth disease]. / Enfermedad respiratoria y parálisis diafragmática en la enfermedad de Charcot-Marie-Tooth.

Diaphragmatic bilateral palsy is uncommon in children. The most important etiologies are thoracic surgery and obstetric trauma. Respiratory muscle impairment is a rare phenomenon in patients with Charcot-Marie-Tooth disease (CMT). However, it can be associated with restrictive pulmonary impairment, phrenic nerve dysfunction or thoracic cage abnormalities. We report two paediatric cases of CMT disease with type 2 respiratory failure due to diaphragmatic dysfunction. In both cases treatment with non-invasive mechanical ventilation resulted in satisfactory clinical improvement. Evidence of phrenic damage was the main clue in one patient in order to obtain an accurate diagnostic of her disease.

[Thymectomy in juvenile myasthenia gravis]. / Timectomía en la miastenia grave juvenil.

INTRODUCTION: Juvenile myasthenia gravis (JMG) is an infrequent autoimmune disease, the symptoms and therapeutic handling of which do not differ from those of the adult forms. Chronic treatment with corticoids very often causes side effects in childhood, which is why patients are being submitted to thymectomies at younger ages with better results. AIMS. To analyse the clinical and evolutionary profile of JMG treated by thymectomy in our centre. PATIENTS AND METHODS: We report the case of four girls aged between 5 and 13 who were diagnosed as suffering from generalised myasthenia gravis (MG) with bulbar affectation. One of them started with a myasthenic crisis. The four of them were submitted to Tensilon s test, an electrophysiological study, determination of AChR, thoracic CT, and study of autoimmunity and thyroid functioning. After surgery the thymus was analysed histologically. RESULTS: They all gave positive in Tensilon s test and were seropositive for AChR. They were treated with anticholinesterases, up to the maximum tolerated dose, and corticoids, without complete remission being accomplished and so they were submitted to a thymectomy in the first year of evolution. In three cases surgical approach was transsternal and in the other by means of a videothoracoscope. All the thymuses showed lymphoid hyperplasia. After a variable follow up the girls are at present asymptomatic, although none of them has been able to completely give up the pharmacological treatment. CONCLUSIONS: Thymectomy is one of the mainstays of treatment for JMG. The ever more frequent use of videothoracoscopic techniques achieves results that are similar to those obtained by conventional surgery but with fewer post operative and aesthetic problems

[Clinical aspects and diagnostic and therapeutic approaches to motor and sensory hereditary neuropathies (NHMS)]. / Aspectos clínicos y abordaje diagnóstico y terapéutico de las neuropatías hereditarias sensitivomotoras.

INTRODUCTION: The classifications of peripheral neuropathies are continually being revised in the light of advances in genetic and biochemical investigation. OBJECTIVE: We establish a classification based on the pathology found in different anatomical structures of nerves: the Schwann cell, myelin, axon and the different genes involved in causing neuropathies. Diagnosis is based on data from the clinical history, physical examination and electromyography and their correlation with the type of inheritance in relation to the different genes localized to (a) the Schwann cell: periaxin gene (PRX) encoding L and S periaxin. Stabilisation of the myelin acting as a signal tranducer. NDRG1 down stream regulated gene 1 and 2 acting as transcription factors in embryogenesis. EGR2/Krox 20 has an important function in myelinization. (b) Myelin: P0 membrane protein zero (MPZ) stabilizes the myelin. P1 myelin basic protein (MBP), is analogous to the myelin protein of the central nervous system (CNS) P2 found in the cytoplasm. PMP22 (peripheral myelin protein) also stabilizes the protein. MAG (myelin associated glycoprotein) has antigenic properties. (c). Axon. A foundational mutation (892C Y) in the gene of the lamina (LMNA) of the light neurofilaments (NF L). Mutations in the KIF1Bb gene which encodes the protein kinesin. We also make an aetiological analysis of some classical syndromes, especially the D jerine Sottas syndrome. CONCLUSION: The systematization used, based on clinical and electrophysiological data in relation to the different genes involved in the various anatomical structures constitutes a logical, diagnostic approach which is very useful.

Aspectos clínicos y abordaje diagnóstico y terapéutico de las neuropatías hereditarias sensitivomotoras / Clinical aspects and diagnostic and therapeutic approaches to motor and sensory hereditary neuropathies (NHMS)

Introducción. La caracterización de las neuropatías periféricas está en continua revisión debido a los avances en la investigación genética y bioquímica. Objetivo. Se establece una caracterización basada en la patología existente en las distintas estructuras anatómicas del nervio: célula de Schwann, mielina, axón y los distintos genes implicados en ellas, causantes de neuropatías. La orientación diagnóstica se basa en los datos obtenidos en la anamnesis, la exploración física y electromiográfica, y su correlación con el tipo de herencia respecto a los distintos genes localizados en: a) Célula de Schwann: periaxin gen (PRX) codifica L y S periaxin, y estabiliza la mielina actuando como transductor de señales; NDRG1/down stream regulated gene 1 y 2 actúan como factores de transcripción en la embriogénesis; EGR2/Krox20 tiene una importante función en la mielinización. b) Mielina: P0 membrane protein zero (MPZ) estabiliza la mielina; P1 myelin basic protein (MBP) es análoga a la proteína mielínica del sistema nervioso central (SNC); P2 se localiza en el citoplasma; PMP22 (peripheral mielin protein) estabiliza también la proteína; MAG (myelin associated glycoprotein) tiene propiedades antigénicas. c) Axón: una mutación fundacional (892C-T) en el gen de la lamina (LMNA) de los neurofilamentos ligeros (NF-L), o light filaments; mutaciones en el gen KIF1B , codificador de la proteína cinesin. Asimismo, se hace un análisis etiológico de algunos síndromes clásicos, especialmente el de Dèjerine-Sottas. Conclusión. La sistematización utilizada, basada en datos clínicos y electrofisiológicos en relación a los distintos genes implicados en las diferentes estructuras anatómicas, constituye un enfoque diagnóstico lógico y de gran utilidad (AU)

Timectomía en la miastenia grave juvenil / Thymectomy in juvenile myasthenia gravis

Introducción. La miastenia grave juvenil (MGJ) es una enfermedad autoinmune infrecuente, cuya clínica y manejo terapéutico no difiere de las formas del adulto. El tratamiento crónico con corticoides provoca, con gran frecuencia, efectos adversos en la infancia, por lo que se recurre a la timectomía cada vez a edades más tempranas y con mejores resultados. Objetivos. Analizar el perfil clínico y evolutivo de la MGJ tratada mediante timectomía en nuestro centro. Pacientes y métodos. Presentamos cuatro niñas, de edades comprendidas entre los 5 y los 13 años, diagnosticadas de miastenia grave generalizada con afectación bulbar. Una de ellas debutó con una crisis miasténica. En todas se realizó: test de Tensilon, estudio electrofisiológico, determinación de AChR, TAC torácica y estudio de autoinmunidad y función tiroidea. Tras la cirugía, el timo se analizó histológicamente. Resultados. Todas presentaron un test de Tensilon positivo y seropositividad para AChR. Recibieron trata miento con anticolinesterásicos, hasta la dosis máxima tolerada, y corticoides, sin llegar a remisión completa, por lo que se timectomizaron en el primer año de evolución. En tres casos se realizó un abordaje transesternal y en uno por videotoracoscopia. Todos los timos mostraron hiperplasia linfoide. Tras un seguimiento variable, las niñas se encuentran actualmente asintomáticas, aunque ninguna ha podido abandonar completamente el tratamiento farmacológico. Conclusiones. La timectomía es uno de los pilares del tratamiento de la MGJ. La utilización cada vez más frecuente de la videotoracoscopia consigue resultados similares a los de la cirugía convencional, con menos problemas postoperatorios y estéticos (AU)

[Severe and mild forms of nemaline myopathy: a report of three cases]. / Miopatía nemalínica: forma congénita neonatal y moderada a propósito de tres observaciones.

Three new cases of two different forms of congenital nemaline myopathy are reported. Two of them represent a severe neonatal form. These cases were presented as a floppy infant syndrome. Although neither of them needed intensive care, they had feeding difficulties and one needed a feeding-tube for a period of time. Both of the patients showed a very severe motor delay and neither could manage to walk independently. During their lives, they suffered from repeated pneumonias, which was the cause of death in both cases before the age of two years. The mild congenital type represents a more benign form. Although hypotonic and weak, the patient managed to walk independently before two years of age. The weakness was spread all over, but was focused in the face, extensors of the neck and axial muscles. At 9 years of age, the patient has not experienced any respiratory trouble. The CK (creatine kinase) test were normal in all patients, but the EMG (electromyogram) showed different electromyographic patterns. The rods were in subsarcolemic positions, cytoplasmic positions or in both positions.

[Specificity of the dystrophin immunohistochemical technique in muscular dystrophy]. / Especificidad de la técnica inmunohistoquímica de la distrofina en las distrofias musculares de Duchenne y de Becker.

We have used a monoclonal antibody against the portion of the dystrophin molecule known as a mid rod using an immunoperoxidase technique in 41 muscle biopsies of patients with different muscle diseases. Twelve of the patients suffered a Xp21 dystrophy, nine of them had the Duchenne type and three the Becker. All the patients affected by a non Xp21 dystrophy had a normal dystrophin labelling pattern in their muscle fibres. The labelling patterns in the Duchenne biopsies were of three types. In seven of them we found no dystrophin at all. One showed only small nuclei of fibres with a normal amount of dystrophin in them. The last patient showed a weak labelling pattern in the majority of his fibres. In the two Becker dystrophy-type biopsies the expression of dystrophin varied. In one of them we could see a clear labelling pattern in all fibres, while the other showed a disruptive pattern with some portions of the sarcolemic membrane without dystrophin. We concluded the report enhancing the enormous support that this technique means particularly in the biopsies of patients suffering from an Xp21 alterations.

[Peripheral neuropathy as a presenting form of Cockayne syndrome]. / Neuropatía periférica como forma de presentación del síndrome de Cockayne.

We report a clinical observation of an infant aged 5 months with Cockayne syndrome whose symptomatology included failure to thrive, microcephaly, peripheral neuropathy and elevated level of protein in CSF. More typical signs of this syndrome appeared lately with progeroid facies, photosensitivity and intracranial calcifications that computed tomography revealed at 13 months of age. The early onset of clinical manifestations, the association with peripheral neuropathy, and the high level of protein in CSF are unusual facts that led us to do the differential diagnosis with other demyelinating disorders.

[Muscular phosphorylase deficiency in two siblings]. / Déficit de fosforilasa muscular en dos hermanos.

The clinical manifestation of McArdle disease rarely occur in children. A brother and a sister aged 12 and 7 years respectively are presented. Both are sons of a consanguinous marriage. The clinical manifestations of the girl began when she was seven. The dominant clinical feature was her difficulty in performing physical exercises. At this time the brother was asymptomatic. There were no abnormalities on physical examination. The level of the serum CK was fluctuating at a level above normal in both patients. There was not lactic acidosis after exercise test. The level of lactic acid didn't rise after McArdle test with ischemia of the forearm in both, however the plasmatic ammonium rose six or seven times above the basal level. The electromyography showed in the girl electric silence without pain and stiffness after ischemia of the forearm. The muscle biopsy performed by a Bergström needle showed in both a subsarcolemmal glycogen accumulations. The histochemical reaction for phosphorylase was absent, the biochemical investigations confirmed the absence of this enzyme. A hyperproteique diet did not release the clinical manifestations of the patients.

[Application of the trigemino-facial reflex in acquired peripheral facial paralysis in childhood]. / Aplicación del reflejo trigémino-facial en la parálisis facial periférica adquirida en la infancia.

The AA report the results of the blink reflex and facial nerve stimulation in 16 children with acquired facial paralysis. Generally these verifications permitted the localization of the most impaired nerve segment and thereafter to give a recovery prognosis.

[Idiopathic inflammatory myopathies in childhood. A study of 7 patients]. / Miopatías inflamatorias idiopáticas en la infancia. Estudio de siete pacientes.

Five patients with dermatomyositis and 2 with polymyositis between 3 and 12 years old are reviewed. All of them fulfil the Bohan and Peter diagnostic criteria. Five presented misery before weakness. Two presented acute renal failure. The pathologic muscular study was not always specific of inflammatory myopathy and without correlation with the degree of symptoms. Treatment which prednisone and in one patient also azathioprine resulted with complete remission in 4 patients.