ABSTRACT
Introducción: El síndrome de Ohtahara (SO, OMIM#308350, ORPHA1934) es una encefalopatía epiléptica de inicio precoz (EEIP) caracterizada por espasmos, crisis epilépticas intratables, un trazado electroencefalográfico de brote-supresión y retraso psicomotor grave. En la mayoría de los pacientes con SO se han identificado mutaciones en el gen STXBP1, que codifica para la proteína de unión a sintaxina 1 y que está implicado en el mecanismo de exocitosis de las vesículas sinápticas. Paciente y resultados: Se presenta el caso clínico de un varón de 19 meses de edad diagnosticado de SO en el que se ha identificado una mutación no descrita (c.1249 + 2T > C, G417AfsX7) en el gen STXBP1. La mutación está localizada en uno de los sitios donadores implicados en el procesamiento del ARNm del gen, lo que produce la pérdida del exón 14 y el posterior truncamiento de la proteína que codifica. Conclusiones: Esta nueva mutación en el gen STXBP1, identificada en un paciente sin lesión cerebral estructural subyacente, amplía el espectro mutacional asociado a este devastador síndrome epiléptico
Introduction: Ohtahara syndrome (OS, OMIM#308350, ORPHA1934) is an early-onset epileptic encephalopathy (EOEE) characterised by spasms, intractable seizures, suppression-burst pattern on the electroencephalogram, and severe psychomotor retardation. Mutations in STXBP1 -a gene that codes for syntaxin binding protein 1 and is involved in synaptic vesicle exocytosis- has been identified in most patients with OS. Patient and results: We report the case of a 19-month-old child with OS who displays a previously unreported mutation in STXBP1 (c.1249 + 2T > C, G417AfsX7). This mutation is located in a donor splice site and eliminates exon 14, resulting in a truncated protein. Conclusion: This previously unreported STXBP1 mutation in a subject with Ohtahara syndrome and non-lesional magnetic resonance imaging (MRI) broadens the mutational spectrum associated with this devastating epileptic syndrome
Subject(s)
Humans , Male , Child , Munc18 Proteins/genetics , Mutation/genetics , Spasms, Infantile/genetics , Exons/genetics , Intellectual Disability/genetics , Intellectual Disability/psychology , Magnetic Resonance Imaging , Spasms, Infantile/diagnostic imaging , Spasms, Infantile/psychologyABSTRACT
INTRODUCTION: Ohtahara syndrome (OS, OMIM#308350, ORPHA1934) is an early-onset epileptic encephalopathy (EOEE) characterised by spasms, intractable seizures, suppression-burst pattern on the electroencephalogram, and severe psychomotor retardation. Mutations in STXBP1 -a gene that codes for syntaxin binding protein 1 and is involved in synaptic vesicle exocytosis- has been identified in most patients with OS. PATIENT AND RESULTS: We report the case of a 19-month-old child with OS who displays a previously unreported mutation in STXBP1 (c.1249+2T>C, G417AfsX7). This mutation is located in a donor splice site and eliminates exon 14, resulting in a truncated protein. CONCLUSION: This previously unreported STXBP1 mutation in a subject with Ohtahara syndrome and non-lesional magnetic resonance imaging (MRI) broadens the mutational spectrum associated with this devastating epileptic syndrome.
Subject(s)
Munc18 Proteins/genetics , Mutation/genetics , Spasms, Infantile/genetics , Child, Preschool , Exons/genetics , Humans , Intellectual Disability/genetics , Intellectual Disability/psychology , Magnetic Resonance Imaging , Male , Spasms, Infantile/diagnostic imaging , Spasms, Infantile/psychologyABSTRACT
Understanding host-pathogen evolutionary dynamics needs characterisation and quantification of processes occurring at many spatiotemporal scales. With this aim, the effects of smut on a naturally infected population of the summer annual Digitaria sanguinalis were followed for 4 years in an uncropped field. The main purpose of the study was to quantify the effects of within-population density on the infectivity and the aggressiveness of the pathogen in a range of densities that occurred naturally. The infectivity-related variable measured was the proportion of smutted plants at the end of each growing season; proportions were analysed using a generalised linear model with a binomial distribution considering the year, the density and their interaction as effects. The aggressiveness-related variables chosen were the number of smutted inflorescences per plant and per area, obtained over the last 2 years; they were analysed by means of ancova considering disease status (seeded or smutted), year, density and all the interactions between them. Although the disease is monocyclic, results showed clearly that infectivity increased with plant density. The number of inflorescences per plant was 1.5 times higher in smutted plants than in healthy plants throughout the range of densities. This variable declined when density increased, but as the infectivity increased at a higher rate, the aggressiveness also increased with density. The surprising results on infectivity are discussed in the context of current knowledge of plant-pathogen interaction dynamics, as well as neighbour effects on pathogen aggressiveness. Moreover, the results could be useful to develop weed biological control strategies.
Subject(s)
Digitaria/microbiology , Host-Pathogen Interactions , Plant Diseases/microbiology , Ustilago/physiology , Biological Evolution , Linear Models , Plant Weeds , Seasons , Ustilago/pathogenicity , VirulenceABSTRACT
Prolonged seizures and status epilepticus are common neurological medical emergencies. Early and appropriate treatment is essential to reduce morbidity and mortality. Most seizures occur in the community, so parents and caregivers must be prepared for their management. Benzodiazepines (BZD) are the first-line drugs used, with rectal diazepam (DZPr) being the most commonly used in pre-hospital treatment in Spain. In September 2011, the European Medicines Agency (EMA) authorized the use of oromucosal midazolam (MDZb) for the treatment of prolonged acute convulsive seizures in patients aged 3 months to <18 years. MDZb has a rapid onset, short duration of effect, and avoids first-pass hepatic metabolism. MDZb has shown to be at least as or more effective than DZPr to stop the seizures. Buccal administration is easier and more socially accepted, especially in adolescents and adults. It is a safe drug with similar effects to other BZD; MDZb improves the overall cost-effectiveness of seizures management.
Subject(s)
Benzodiazepines/therapeutic use , Seizures/drug therapy , Status Epilepticus/drug therapy , Child , Community Health Services , Humans , Status Epilepticus/physiopathologyABSTRACT
Las crisis prolongadas y el estado epiléptico son emergencias médicas neurológicas frecuentes y su tratamiento adecuado y precoz es fundamental para reducir su morbi-mortalidad. La mayoría de las crisis se inician en un medio extrahospitalario, lo que obliga a familiares y cuidadores a estar preparados en las medidas de actuación iniciales ante una crisis convulsiva. En su manejo, las benzodiacepinas (BZD) son los fármacos de primera línea, siendo el uso de diazepam rectal (DZPr) el más extendido en el ámbito prehospitalario en España. La Agencia Europea del Medicamento (EMA) autorizó en septiembre del 2011 el empleo de midazolam bucal (MDZb) para el manejo de las crisis epilépticas repetidas en pacientes entre los 3 meses y 18 años. Es un fármaco de acción rápida por evitar la metabolización hepática y con efecto de corta duración. MDZb ha demostrado al menos igual o mayor eficacia que el DZPr y la vía de administración bucal es más sencilla y mejor aceptada socialmente, sobre todo en adolescentes y adultos. Es un fármaco seguro, con efectos adversos similares a otras BZD. Estudios de farmacoeconomía demuestran un buen coste-efectividad global en el manejo de las crisis frente al DZPr, reduciendo traslados en ambulancia e ingresos hospitalarios
Prolonged seizures and status epilepticus are common neurological medical emergencies. Early and appropriate treatment is essential to reduce morbidity and mortality. Most seizures occur in the community, so parents and caregivers must be prepared for their management. Benzodiazepines (BZD) are the first-line drugs used, with rectal diazepam (DZPr) being the most commonly used in pre-hospital treatment in Spain. In September 2011, the European Medicines Agency (EMA) authorized the use of oromucosal midazolam (MDZb) for the treatment of prolonged acute convulsive seizures in patients aged 3 months to < 18 years. MDZb has a rapid onset, short duration of effect, and avoids first-pass hepatic metabolism. MDZb has shown to be at least as or more effective than DZPr to stop the seizures. Buccal administration is easier and more socially accepted, especially in adolescents and adults. It is a safe drug with similar effects to other BZD; MDZb improves the overall cost-effectiveness of seizures management
Subject(s)
Humans , Benzodiazepines/therapeutic use , Epilepsy/drug therapy , Seizures/drug therapy , Status Epilepticus/drug therapy , 50303 , Midazolam/therapeutic useABSTRACT
OBJECTIVE: To design, implement and assess a clinical pathway for lower-extremity deep venous thrombosis, and to compare the length of hospital stay in two different periods. DESIGN: Development of the care pathway by a multidisciplinary team, followed by a controlled intervention study to compare two non-concomitant cohorts of patients corresponding to the years 2002 (before the implementation of the critical pathway) and 2004 (year of the implementation). SETTING: Academic tertiary care hospital. PARTICIPANTS: 90 patients, 42 corresponding to the year 2004 and 48 to 2002, admitted to hospital with a diagnosis of lower-extremity deep venous thrombosis (DVT). MAIN OUTCOME MEASURES: Length of hospital stay, hospitalisation costs and care indicators. RESULTS: The mean length of hospital stay was 6.78 days in 2002 and 4.72 days in 2004. This means a reduction of 2.06 days (p<0.012). The reduction in the length of hospital stay in 2004 situates the hospital 1.98 days below the mean stay of our community (6.7 days) for the same diagnosis and year. The impact of the clinical pathway was assessed using the following indicators: implementation indicator 92.2%, compliance indicator 65%, adverse events indicator 2.5% and satisfaction indicator 67%. In comparison with costs incurred in year 2002, implementation of the clinical pathway resulted in a saving of euro427.33 per patient and a total saving of euro17,093.20. CONCLUSIONS: The implementation of a lower-extremity DVT clinical pathway in our institution has help to reduce hospitalisation costs, due to a decreased length of hospital stay.
Subject(s)
Critical Pathways/economics , Health Care Costs , Lower Extremity , Venous Thrombosis/economics , Venous Thrombosis/therapy , Academic Medical Centers/organization & administration , Aged , Aged, 80 and over , Evidence-Based Medicine , Female , Humans , Length of Stay , Male , Middle Aged , Venous Thrombosis/prevention & controlABSTRACT
Neurobehavioral manifestations of complete HPRT deficiency include severe action dystonia, choreathetosis, alteration of executive functions, and self-injurious behavior. Dystonic manifestations are also present in patients with partial HPRT deficiency. Pathophysiology of these manifestations is unknown. Guanidinoacetate is a neurotoxin implicated in certain dystonic syndromes. We have examined guanidinoacetate and creatine levels in urine from 11 HPRT deficient patients (9 with Lesch-Nyhan syndrome and 2 with partial deficiency). Urinary guanidinoacetate and creatine levels in HPRT deficient patients were within the normal range. Guanidinoactetate alteration does not seem to be implicated in the pathogenesis of the neurological disease associated with HPRT deficiency.
Subject(s)
Creatine/urine , Glycine/analogs & derivatives , Hypoxanthine Phosphoribosyltransferase/deficiency , Lesch-Nyhan Syndrome/urine , Creatinine/urine , Glycine/urine , Humans , Lesch-Nyhan Syndrome/enzymologyABSTRACT
El nevus comedónico es un hamartoma folicular poco frecuente, caracterizado por la presencia de pápulas agminadas con orificio central ocupado por material córneo. Presentamos tres casos de esta rara dermatosis, con una disposición clínica siguiendo las líneas de Blaschko. Se discuten sus asociaciones, dignósticos deferenciales y tratamiento.
Subject(s)
Humans , Male , Adult , Female , Child , Hamartoma , Nevus , TretinoinABSTRACT
El nevus comedónico es un hamartoma folicular poco frecuente, caracterizado por la presencia de pápulas agminadas con orificio central ocupado por material córneo. Presentamos tres casos de esta rara dermatosis, con una disposición clínica siguiendo las líneas de Blaschko. Se discuten sus asociaciones, dignósticos deferenciales y tratamiento.(AU)
Subject(s)
Humans , Male , Adult , Female , Child , Nevus/classification , Nevus/nursing , Hamartoma/classification , Hamartoma/nursing , Hamartoma/therapy , Tretinoin/administration & dosageABSTRACT
AIMS: To assess the association between prenatal exposure to organochlorine compounds and thyroid status in newborns from an area with high levels of hexachlorobenzene (HCB). METHODS: A total of 98 mother-infant pairs (83.1% of all children born during the period 1997-99 in a specific area polluted with HCB) were recruited. Levels of organochlorine compounds were measured in 70 cord serum samples. Concentrations of thyroid stimulating hormone (TSH) were measured in plasma of all newborns three days after birth. RESULTS: All newborns had concentrations of TSH within the range of normal reference values (<25 mU/l). Dichlorodiphenyl dichloroethylene (p,p'DDE), beta-hexachlorocyclohexane (beta-HCH), polychlorinated biphenyl (PCB) 138 and 118 were related to higher concentrations of TSH, although only significant for beta-HCH. Levels of HCB were not associated with TSH. CONCLUSIONS: Although this community is highly exposed to HCB, no association was found between this organochlorine and TSH concentrations at birth.
Subject(s)
Air Pollutants/blood , Hydrocarbons, Chlorinated , Infant, Newborn/blood , Insecticides/blood , Thyrotropin/blood , Air Pollutants/pharmacology , Female , Fetal Blood/chemistry , Humans , Insecticides/pharmacology , Male , Maternal-Fetal Exchange , Pregnancy , Prenatal Exposure Delayed Effects , Thyroid Gland/drug effects , Thyroid Gland/physiologyABSTRACT
Hexachlorobenzene (HCB) is an organochlorine compound widespread in the environment, highly lipophilic, that accumulates in biological systems. It has been suggested that it should be classified as a dioxin-like compound. Newborns are exposed to organochlorine compounds across the placenta and through breastfeeding. Although HCB is one of the most common organochlorine compounds, the transplacental transference of HCB from mother to fetus during pregnancy has been scarcely documented. This study reports the levels of HCB, dichlorodiphenyl trichloroethane (DDT) and its metabolite p,p'DDE, polychlorinated biphenyls (PCBs), and beta-hexachlorocyclohexane (beta-HCH) in 72 maternal blood samples at delivery and in 69 cord blood samples, from which 62 corresponded to mother infant pairs born between May 1997 and September 1999 in a rural area highly exposed to HCB. Results show that all newborns presented detectable levels of HCB, PCBs, and p,p'DDE, and, to a lesser extent, of beta-HCH, the HCB levels being the highest. The geometric mean of HCB was 1.1 ng/ml, ranging from 0.3 to 5.7 ng/ml. Concentrations of HCB levels in cord blood (log ng/ml) were positively associated with concentrations in maternal blood (log ng/ml) (coefficient = 0.45, P < 0.01). Gestational age was not associated with the transplacental transfer of HCB. Maternal p,p'DDE and beta-HCH levels were also associated with newborn levels, but levels of PCBs were not. We conclude that HCB, similar to other organochlorinated compounds, has a transplacental transfer.
Subject(s)
Fetal Blood/chemistry , Fungicides, Industrial/pharmacokinetics , Hexachlorobenzene/pharmacokinetics , Maternal-Fetal Exchange , Adult , DDT/analysis , DDT/pharmacokinetics , Dichlorodiphenyl Dichloroethylene/analysis , Dichlorodiphenyl Dichloroethylene/pharmacokinetics , Environmental Exposure , Environmental Pollutants , Female , Fungicides, Industrial/analysis , Hexachlorobenzene/analogs & derivatives , Hexachlorobenzene/analysis , Humans , Infant, Newborn , Insecticides/analysis , Insecticides/pharmacokinetics , Male , Polychlorinated Biphenyls/analysis , Polychlorinated Biphenyls/pharmacokinetics , PregnancyABSTRACT
INTRODUCTION: The association of external capillary hemangiomas with intracranial malformations (vascular or nonvascular) was first described by Pascual-Castroviejo in 1978. The commonest anomalies found included: Dandy-Walker syndrome, cerebellar hypoplasia, arterial angiomas and alterations in the origin or distribution of the main cerebral arteries. In 1996 the same author named it the 'hemangiovascular complex syndrome'. The syndrome association is very similar, perhaps even identical, to that recently described in the English literature under the heading of PHACE. CLINICAL CASES: We describe two new cases of facial hemangioma, Dandy-Walker type posterior fossa malformation and hypoplasia of the carotid-vertebral trunk ipsilateral to the facial hemangioma. The first patient, a three year old girl had needed a ventriculo-peritoneal shunt for hydrocephalus secondary to a Dandy-Walker malformation. During the third month she had severe symptoms of laryngeal obstruction due to the angiomatous lesion and was satisfactorily treated with corticosteroids. At the present time her psychomotor development seems normal on neurological examination and evaluation. The second patient, a thirteen year old boy, besides showing the characteristic features of this syndrome also had attention-deficit hyperactivity and clumsy movements. In both cases the facial hemangioma was present at birth and gradually became smaller although it did not disappear completely. CONCLUSION: It is important to know about this neurocutaneous syndrome to avoid confusion with similar conditions such as the Sturge-Weber syndrome, so as to carry out suitable clinical investigations: cerebral magnetic resonance, angio-resonance of the intracranial vessels and supra-aortic trunks, arteriography, echocardiography and ophthalmological assessment and to prevent signs of upper respiratory tract obstruction which may be very serious.
Subject(s)
Abnormalities, Multiple , Carotid Arteries/abnormalities , Cranial Fossa, Posterior/abnormalities , Dandy-Walker Syndrome , Facial Neoplasms/congenital , Hemangioma/congenital , Vertebral Artery/abnormalities , Abnormalities, Multiple/pathology , Adolescent , Attention Deficit Disorder with Hyperactivity/etiology , Carotid Arteries/pathology , Child, Preschool , Dandy-Walker Syndrome/surgery , Facial Neoplasms/pathology , Female , Hemangioma/pathology , Humans , Learning Disabilities/etiology , Magnetic Resonance Angiography , Psychomotor Performance , Syndrome , Ventriculoperitoneal Shunt , Vertebral Artery/pathologyABSTRACT
Activated protein C resistance, usually because of factor V Leiden mutation, is considered to be the most common hereditary prothrombotic condition. A 9-year-old male with a basilar artery stroke and activated protein C resistance is described. The patient, found to be heterozygous for factor V Leiden mutation, is one of several recent reports that suggest that activated protein C resistance is an important risk factor for spontaneous arterial thrombosis in infancy and childhood.
Subject(s)
Activated Protein C Resistance/genetics , Basilar Artery , Factor V/genetics , Intracranial Embolism/genetics , Activated Protein C Resistance/diagnosis , Basilar Artery/pathology , Cerebral Angiography , Child , Genetic Carrier Screening , Humans , Intracranial Embolism/diagnosis , Magnetic Resonance Imaging , MaleABSTRACT
Introducción. La asociación de hemangiomas capilares externos con malformaciones intracraneales (vasculares y no vasculares) fue descrita por primera vez por Pascual-Castroviejo en 1978, siendo las anomalías más frecuentemente encontradas: síndrome de Dandy-Walker, hipoplasia cerebelosa, angiomas arteriales y alteraciones en el origen o la distribución de las arterias cerebrales principales. En 1996 este mismo autor lo denomina `síndrome complejo hemangiovascular'. Esta asociación sindrómica es muy parecida, o quizás idéntica, a la descrita recientemente con el acrónimo PHACE en la literatura anglosajona. Casos clínicos. Aportamos dos nuevos casos que presentan hemangioma facial, malformación de fosa posterior de tipo Dandy-Walker e hipoplasia del eje carotidovertebral ipsilateral al hemangioma facial. El primero de ellos, una niña de 3 años, precisó en los primeros meses de vida una derivación ventriculoperitoneal por la hidrocefalia secundaria a su malformación de Dandy-Walker. En el tercer mes presentó síntomas graves de obstrucción laríngea por componente angiomatoso a ese nivel, evolucionando favorablemente con corticoterapia. Actualmente la exploración neurológica y su desarrollo psicomotor es normal. El segundo, un varón de 13 años, presenta, además de los hallazgos característicos Pascual-Castroviejo I es la displasia cerebro-facio-torácica descrita por este autor en 1975 [13].Nuestros dos pacientes son dos nuevos ejemplos de este síndrome, con unas características muy similares entre sí, pues ambos presentan hemangioma capilar facial, malformación de fosa posterior e hipoplasia de arterias carótida y vertebral ipsilateral al hemangioma. Podríamos considerarlos como pacientes tipo, ya que las otras malformaciones suelen ser menos frecuentes (cardiopatía congénita, anomalías oculares y defectos de cierre abdominal).Por último, recomendamos en todo niño con un hemangioma facial (capilar o cavernoso) la realización de RM cerebral, angio-RM de vasos intracraneales y troncos supraórticos o arteriografía, ecocardiografía y valoración oftalmológica. Debe vigilarse también en estos niños la posible aparición de síntomas de obstrucción de las vías respiratorias altas (estridor, cianosis, dificultad respiratoria), dada la frecuente extensión de estos hemangiomas a la laringe y la parte superior de la traquea, que pueden llegar a comprometer su vida, como ocurrió en uno de nuestros pacientes y en otros casos publicados [5,10]. de este síndrome, un cuadro de déficit de atención con hiperactividad y torpeza motora. En ambos el hemangioma facial estaba presente en el nacimiento y fue desapareciendo lentamente, pero sin llegar a suprimirse de forma completa. Conclusión. Es importante el conocimiento de este síndrome neurocutáneo para evitar la confusión con cuadros similares como el síndrome de Sturge-Weber, para poder realizar las pruebas complementarias adecuadas: resonancia magnética cerebral, angiorresonancia de vasos intracraneales y troncos supraórticos o arteriografía, ecocardiografía y valoración oftalmológica, y para prevenir la aparición de síntomas de obstrucción de vías altas que pueden ser muy graves (AU)
Subject(s)
Child, Preschool , Adolescent , Female , Humans , Dandy-Walker Syndrome , Abnormalities, Multiple , Vertebral Artery , Syndrome , Magnetic Resonance Angiography , Ventriculoperitoneal Shunt , Psychomotor Performance , Attention Deficit Disorder with Hyperactivity , Carotid Arteries , Cranial Fossa, Posterior , Learning Disabilities , Hemangioma , Facial NeoplasmsABSTRACT
BACKGROUND: Bile duct injury (BDI) is a severe complication of laparoscopic cholecystectomy (LC) that is probably related to the effects of the learning curve. The aim of this prospective, institutional, and longitudinal study is to compare the incidence of BDI during LC in relation to the progressive experience of surgeons. METHODS: A total of 784 LC were examined during a 6-year period. They were divided into the following three consecutive groups: group A (1993-94), group B (1995-96), and group C (1997-98). Incidence and type of BDI, experience of the surgeon, intra- or postoperative diagnosis, treatment performed to repair the injury, and early and late morbidity and mortality were evaluated. RESULTS: The overall incidence of BDI was 1.4%. There were three cases of transection of the common bile duct, four partial lesions of the bile duct, and four cystic leakages. The number of BDI was maintained over the three different time periods; there were no statistical differences in the proportion of injuries among groups. Most BDI were incurred by experienced surgeons. In all, 36% of BDI were recognized intraoperatively. Hepaticojejunostomy, direct suture over a T-tube, and closure of the cystic stump were done to repair BDI. There was no additional morbidity or mortality in the patients with BDI. CONCLUSIONS: No relation was found between the experience of the surgeon and the number of BDI over the different periods of time. Therefore, BDI during LC cannot be attributed solely to the learning curve.
Subject(s)
Bile Ducts/injuries , Cholecystectomy, Laparoscopic , Intraoperative Complications/epidemiology , Adult , Aged , Clinical Competence , Female , Humans , Intraoperative Complications/prevention & control , Male , Middle Aged , Prospective Studies , Time FactorsABSTRACT
PURPOSE: This study was conducted to report the rare presentation of lumbar osteomyelitis and epidural abscess as a complication of a pilonidal cyst. METHODS: A case report is presented. RESULTS: We describe the rare case of a male patient with diabetes with a recurring pilonidal cyst who developed a lumbar osteomyelitis and epidural abscess three weeks after pilonidal cyst excision with epidural anesthesia, with a fatal outcome despite emergency treatment. CONCLUSIONS: Life-threatening complications should be kept in mind in high-risk patients with repetitive surgery and neurologic involvement.
Subject(s)
Epidural Abscess/complications , Lumbar Vertebrae , Osteomyelitis/complications , Pilonidal Sinus/complications , Fatal Outcome , Humans , Magnetic Resonance Imaging , Male , Middle Aged , RecurrenceABSTRACT
Propionic acidaemia (PA) is an autosomal recessive disorder caused by mutations in either of the PCCA or PCCB genes which encode the alpha and beta subunits, respectively, of the mitochondrial enzyme propionyl-CoA carboxylase (PCC). In this work we have examined the biochemical findings and clinical outcome of 37 Spanish PA patients in relation to the mutations found in both PCCA and PCCB genes. We have detected 27 early-onset and 101 late-onset cases, showing remarkably similar biochemical features without relation to either the age of onset of the disease or the defective gene they have. Twenty-one of the patients have so far survived and three of them, now adolescents, present normal development. Different biochemical procedures allowed us to identify the defective gene in 9 PCCA deficient and 28 PCCB deficient patients. Nine putative disease-causing mutations accounting for 77.7% of mutant alleles were identified among PCCA deficient patients, each one carrying a unique genotypic combination. Of PCCB mutant alleles 98% were characterised. Four common mutations (ins/del, E168K, 1170insT and A497V) were found in 38/52 mutant chromosomes investigated, whereas the remainder of the alleles harbour 12 other different mutations. By examining the mutations identified both in PCCA and PCCB genes and the clinical evolution of patients, we have found a good correlation between certain mutations which can be considered as null with a severe phenotype, while certain missense mutations tend to be related to the late and mild forms of the disease. Expression studies, particularly of the missense mutations identified are necessary but other genetic and environmental factors probably contribute to the phenotypic variability observed in PA.
Subject(s)
Carboxy-Lyases/deficiency , Adult , Biotin/metabolism , Blotting, Northern , Blotting, Western , Carboxy-Lyases/genetics , Cells, Cultured , DNA Mutational Analysis , Female , Genetic Complementation Test , Genotype , Humans , Male , Methylmalonyl-CoA Decarboxylase , Phenotype , Spain , Treatment Outcome , TritiumABSTRACT
INTRODUCTION: Lhermitte-Duclos disease is a rare lesion characterized by enlarged cerebellar folia containing abnormal ganglion cells. It typically affects young adults, and reports in the pediatric age are exceptional. CLINICAL CASE: This case report describes a child with slowly progressive macrocephaly, which was already present at birth, delayed motor development, and clumsiness. At 7 years of age a mild ataxia appeared, which remained stationary until 10 years of age when he developed signs of intracranial pressure (headache and papilloedema). A CT scan at 2 years of age showed an enlarged posterior fossa with asymmetrical cerebellum; another study at 7 years of age disclosed mild ventricular dilatation. IRM at 10 years of age showed aqueductal obliteration by an enlarged cerebellum. The cerebellar lesion consisted of abnormally thickened folia with abnormal hyperintensity of the central cerebellum on the T2-weighted images. The lesion did not enhance with gadolinium. The histological findings were typical of Lhermitte-Duclos disease. CONCLUSIONS: In our patient the lesion behaved like a slowly growing mass, but both neuroimaging and pathological studies were suggestive of a hamartomatous rather than a true neoplastic disorder. Furthermore, there was clinical evidence that the disorder was already present at birth. All the evidences in our case support the concept that this growing lesion represents a congenital abnormality.