RESUMEN
Although there are many types of inborn errors of metabolism (IEMs) affecting the central nervous system, also referred to as neurometabolic disorders, individual cases are rare, and their diagnosis is often challenging. However, early diagnosis is mandatory to initiate therapy and prevent permanent long-term neurological impairment or death. The clinical course of IEMs is very diverse, with some diseases progressing to acute encephalopathy following infection or fasting while others lead to subacute or slowly progressive encephalopathy. The diagnosis of IEMs relies on biochemical and genetic tests, but neuroimaging studies also provide important clues to the correct diagnosis and enable the conditions to be distinguished from other, more common causes of encephalopathy, such as hypoxia-ischemia. Proton magnetic resonance spectroscopy (1H-MRS) is a powerful, non-invasive method of assessing neurological abnormalities at the microscopic level and can measure in vivo brain metabolites. The present review discusses neuroimaging findings, including those of 1H-MRS, of IEMs focusing on intoxication disorders such as urea cycle disorders, aminoacidopathies, and organic acidopathies, which can result in acute life-threatening metabolic decompensation or crisis.
Asunto(s)
Encefalopatías , Errores Innatos del Metabolismo , Trastornos Innatos del Ciclo de la Urea , Humanos , Errores Innatos del Metabolismo/diagnóstico por imagen , Errores Innatos del Metabolismo/terapia , Trastornos Innatos del Ciclo de la Urea/diagnóstico por imagen , Neuroimagen/métodos , Diagnóstico Precoz , Encefalopatías/diagnóstico por imagenAsunto(s)
Encéfalo/diagnóstico por imagen , Errores Innatos del Metabolismo/diagnóstico por imagen , Vaina de Mielina/patología , Pirofosfatasas/deficiencia , Encefalopatías/complicaciones , Encefalopatías/diagnóstico por imagen , Cerebelo/diagnóstico por imagen , Imagen de Difusión por Resonancia Magnética , Epilepsia/complicaciones , Epilepsia/diagnóstico por imagen , Femenino , Humanos , Lactante , Errores Innatos del Metabolismo/complicaciones , Microcefalia/diagnóstico por imagenRESUMEN
A 5-year-old girl presented with treatment-refractory dry eye and recurrent episodes of eye pain. She had been previously diagnosed with syndromic congenital sodium diarrhea (SCSD) caused by a pathogenic variant in SPINT2. Her local pediatric ophthalmologist had made the diagnosis of severe dry eye with corneal erosions, based on which, we arranged an eye exam under anesthesia (EUA) and punctal plug placement. Anterior segment optical coherence tomography (OCT) and corneal photographs were taken during the procedure. There are reports describing similar ophthalmic findings in this syndrome. However, to the best of our knowledge, this is the first case report to document OCT imaging and corneal photographs in a patient with SCSD, which we feel expands the ophthalmic phenotype of this rare genetic disorder.
Asunto(s)
Anomalías Múltiples/genética , Diarrea/congénito , Glicoproteínas de Membrana/genética , Errores Innatos del Metabolismo/genética , Sodio/metabolismo , Anomalías Múltiples/diagnóstico , Anomalías Múltiples/diagnóstico por imagen , Anomalías Múltiples/patología , Preescolar , Córnea/metabolismo , Córnea/patología , Diarrea/diagnóstico , Diarrea/diagnóstico por imagen , Diarrea/genética , Diarrea/patología , Humanos , Errores Innatos del Metabolismo/diagnóstico , Errores Innatos del Metabolismo/diagnóstico por imagen , Errores Innatos del Metabolismo/patología , Mutación/genética , Fenotipo , Tomografía de Coherencia Óptica/métodosRESUMEN
Fumarase deficiency (FD) is a rare and severe autosomal disorder, caused by inactivity of the enzyme fumarase, due to biallelic mutations of the fumarase hydratase (FH) gene. Several pathogenic mutations have been published. The article describes an infant with failure to thrive, microcephaly, axial hypotonia, and developmental retardation with increased excretion of fumarate, no activity of fumarase and a homozygous mutation of the FH gene, which was until recently only known as a variant of unknown significance. Carriers of pathogenic mutations in the FH gene are at risk for developing renal cell carcinoma and should therefore be screened. Both parents were healthy carriers of the mutation and had decreased levels of enzyme activity. In addition, the article presents an overview and analysis of all cases of FD reported thus far in the literature.
Asunto(s)
Fumarato Hidratasa/deficiencia , Fumarato Hidratasa/genética , Errores Innatos del Metabolismo/genética , Errores Innatos del Metabolismo/patología , Hipotonía Muscular/genética , Hipotonía Muscular/patología , Trastornos Psicomotores/genética , Trastornos Psicomotores/patología , Humanos , Lactante , Masculino , Errores Innatos del Metabolismo/diagnóstico por imagen , Hipotonía Muscular/diagnóstico por imagen , Trastornos Psicomotores/diagnóstico por imagenRESUMEN
SGPL1 encodes sphingosine-1-phosphate lyase, the final enzyme of sphingolipid metabolism. In 2017, a condition featuring steroid-resistant nephrotic syndrome and/or adrenal insufficiency associated with pathogenic SGPL1 variants was reported. In addition to the main features of the disease, patients often exhibit a range of neurologic deficits. In a handful of cases, brain imaging results were described. However, high-quality imaging results and a systematic analysis of brain MR imaging findings associated with the condition are lacking. In this study, MR images from 4 new patients and additional published case reports were reviewed by a pediatric neuroradiologist. Analysis reveals recurring patterns of features in affected patients, including isolated callosal dysgenesis and prominent involvement of the globus pallidus, thalamus, and dentate nucleus, with progressive atrophy and worsening of brain lesions. MR imaging findings of abnormal deep gray nuclei, microcephaly, or callosal dysgenesis in an infant or young child exhibiting other typical clinical features of sphingosine-1-phosphate lyase insufficiency syndrome should trigger prompt genetic testing for SGPL1 mutations.
Asunto(s)
Aldehído-Liasas/deficiencia , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Errores Innatos del Metabolismo/diagnóstico por imagen , Errores Innatos del Metabolismo/patología , Aldehído-Liasas/genética , Niño , Preescolar , Femenino , Humanos , Lactante , Imagen por Resonancia Magnética , Masculino , Errores Innatos del Metabolismo/genética , Mutación , Síndrome Nefrótico/enzimología , Síndrome Nefrótico/genética , Síndrome Nefrótico/patologíaRESUMEN
Neonatal brain sonography is part of routine clinical practice in neonatal intensive care units, but ultrasound imaging of the posterior fossa has gained increasing attention since the burden of perinatal acquired posterior fossa abnormalities and their impact on motor and cognitive neurodevelopmental outcome have been recognized. Although magnetic resonance imaging (MRI) is often superior, posterior fossa abnormalities can be suspected or detected by optimized cranial ultrasound (CUS) scans, which allow an early and bed-side diagnosis and monitoring through sequential scans over a long period of time. Different ultrasound appearances and injury patterns of posterior fossa abnormalities are described according to gestational age at birth and characteristics of the pathogenetic insult. The aim of this review article is to describe options to improve posterior fossa sequential CUS image quality, including the use of supplemental acoustic windows, to show standard views and normal ultrasound anatomy of the posterior fossa, and to describe the ultrasound characteristics of acquired posterior fossa lesions in preterm and term infants with effect on long-term outcome. The limitations and pitfalls of CUS and the role of MRI are discussed.
Asunto(s)
Encéfalo/anomalías , Encéfalo/diagnóstico por imagen , Cerebelo/diagnóstico por imagen , Fosa Craneal Posterior/diagnóstico por imagen , Ecoencefalografía/métodos , Ultrasonografía/métodos , Hemorragia Cerebral/complicaciones , Hemorragia Cerebral/diagnóstico por imagen , Humanos , Procesamiento de Imagen Asistido por Computador , Recién Nacido , Recien Nacido Prematuro , Enfermedades del Prematuro/diagnóstico por imagen , Imagen por Resonancia Magnética , Meningitis/diagnóstico por imagen , Errores Innatos del Metabolismo/diagnóstico por imagen , Streptococcus agalactiaeRESUMEN
OBJECTIVE: To evaluate diagnostic capability of brain magnetic resonance imaging (MRI) in detection of inherited neurometabolic disorders. METHODS: This retrospective observational study was performed in Radiology Department at our Hospital in Dhahran, from January 2013 to January 2020. We evaluated brain MRIs of children (under 5) who were referred to pediatric neurology for clinical suspicion of neuro-developmental delay and metabolic disease. Known perinatal ischemia and birth trauma cases were excluded. Imaging criteria included: (i) bilateral symmetric white matter signal abnormality, (ii) diffusion restriction affecting bilateral deep grey nuclei with or without brainstem involvement, (iii) brain atrophy or edema with abnormal white matter signal, (iv) characteristic MR spectroscopic finding. Presence of any one of these findings was considered positive for neurometabolic disease. Two neuroradiologists interpreted MRIs with substantial interobserver agreement. Diagnoses were confirmed on biochemical/ metabolic screening and genetic testing. A 2 x 2 contingency table was used for results. Chi square test was used to determine association. RESULTS: Out of 133 cases, 72 (49 males, 90% AR) were found to have neurometabolic disorders. Sensitivity, specificity, positive and negative predictive values were calculated as 81.94% (CI, 71.11-90.02), 67.21% (CI, 54.00-78.69), 74.68% (CI, 66.96-81.11) and 75.93% (CI, 65.16-84.17) respectively. Findings were found significant (p-value=0.0001). CONCLUSION: Brain MRI can help to predict inherited neurometabolic disorders considering certain findings.
Asunto(s)
Encefalopatías Metabólicas/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Errores Innatos del Metabolismo/diagnóstico por imagen , Neuroimagen/métodos , Preescolar , Femenino , Humanos , Lactante , Masculino , Estudios RetrospectivosRESUMEN
BACKGROUND: Trimethylaminuria (TMAU) is a metabolic disorder characterized by the excessive excretion of the malodorous compound trimethylamine (TMA). The diagnosis of TMAU is challenging because this disorder is situated at the boundary between biochemistry and psychiatry. Here, we used nuclear magnetic resonance spectroscopy to assess TMAU in 13 patients. We also sequenced the FMO3 gene in 11 of these patients. Treatment with vitamin B2 was prescribed. RESULTS: Two patients (aged 3 and 9 years at the initial consultation) had a particularly unpleasant body odor, as assessed by their parents and the attending physicians. The presence of high urine TMA levels confirmed the presence of a metabolic disorder. The two (unrelated) children carried compound heterozygous variants in the FMO3 gene. In both cases, vitamin B2 administration decreased TMA excretion and reduced body odor. The 11 adults complained of an unpleasant body odor, but the physicians did not confirm this. In all adult patients, the urine TMA level was within the normal range reported for control (non-affected) subjects, although two of the patients displayed an abnormally high proportion of oxidized TMA. Seven of the 9 tested adult patients had a hypomorphic variant of the FMO3 gene; the variant was found in the homozygous state, in the heterozygous state or combined with another hypomorphic variant. All 11 adults presented a particular psychological or psychiatric phenotype, with a subjective perception of unpleasant odor. CONCLUSIONS: The results present the clinical and biochemical data of patients complaining of unpleasant body odor. Contrary to adult patients, the two children exhibited all criteria of recessively inherited trimethylaminuria, suspected by parents in infancy. B2 vitamin treatment dramatically improved the unpleasant body odor and the ratio of TMA/Cr vs TMAO/Cr in the urine in the children. Other patients presented a particular psychological or psychiatric phenotype.
Asunto(s)
Pruebas Genéticas/métodos , Espectroscopía de Resonancia Magnética/métodos , Errores Innatos del Metabolismo/diagnóstico por imagen , Errores Innatos del Metabolismo/diagnóstico , Metilaminas/orina , Riboflavina/uso terapéutico , Niño , Preescolar , Humanos , Errores Innatos del Metabolismo/tratamiento farmacológico , Errores Innatos del Metabolismo/genética , Oxigenasas/genética , FenotipoRESUMEN
Inborn errors of metabolism, also known as inherited metabolic diseases, constitute an important group of conditions presenting with neurologic signs in newborns. They are individually rare but collectively common. Many are treatable through restoration of homeostasis of a disrupted metabolic pathway. Given their frequency and potential for treatment, the clinician should be aware of this group of conditions and learn to identify the typical manifestations of the different inborn errors of metabolism. In this review, we summarize the clinical, laboratory, electrophysiologic, and neuroimaging findings of the different inborn errors of metabolism that can present with florid neurologic signs and symptoms in the neonatal period.
Asunto(s)
Enfermedades del Recién Nacido/terapia , Errores Innatos del Metabolismo/terapia , Adulto , Femenino , Humanos , Recién Nacido , Enfermedades del Recién Nacido/diagnóstico , Enfermedades del Recién Nacido/diagnóstico por imagen , Enfermedades del Recién Nacido/fisiopatología , Errores Innatos del Metabolismo/diagnóstico , Errores Innatos del Metabolismo/diagnóstico por imagen , Errores Innatos del Metabolismo/fisiopatología , Neuroimagen , EmbarazoRESUMEN
BACKGROUND: Phosphoglycerate kinase-1 deficiency is caused by X-linked recessive mutations in PGK-1 and associated with haemolytic anaemia, rhabdomyolysis, myopathy and nervous system involvement. Some cases have been rarely associated with juvenile Parkinsonism however the causal relationship between PGK1 deficiency and nigrostriatal dysfunction causing Parkinsonism has not been determined. OBJECTIVE AND METHODS: To investigate the nigrostriatal system using 99mTc-TRODAT-1 SPECT binding and report the phenotype of three affected males with early onset levodopa responsive Parkinsonism harbouring the c.491 Aâ¯>â¯T/p.D164V pathogenic variant. RESULTS: All patients initially presented with infantile-onset encephalopathic and stroke-like episodes, haemolytic anaemia and epilepsy. Two patients had an early-onset and one juvenile-onset levodopa responsive Parkinsonism with motor fluctuations. 99mTc-TRODAT-1 SPECT showed severe bilateral reduced putaminal uptake in the three patients. None of the patients had structural lesions that could explain either pre- or postsynaptic dopaminergic dysfunction. CONCLUSION: These cases provide strong evidence of a causal relationship between PGK1 deficiency and nigrostriatal pathology causing Parkinsonism. These findings have potential implications for our understanding of the pathophysiology of nigrostriatal degeneration in sporadic PD.
Asunto(s)
Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Enfermedades Genéticas Ligadas al Cromosoma X/metabolismo , Errores Innatos del Metabolismo/metabolismo , Trastornos Parkinsonianos/metabolismo , Trastornos Parkinsonianos/fisiopatología , Fosfoglicerato Quinasa/deficiencia , Putamen/metabolismo , Sustancia Negra/metabolismo , Adulto , Edad de Inicio , Anemia Hemolítica/etiología , Enfermedades Genéticas Ligadas al Cromosoma X/complicaciones , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico por imagen , Humanos , Masculino , Errores Innatos del Metabolismo/complicaciones , Errores Innatos del Metabolismo/diagnóstico por imagen , Compuestos de Organotecnecio , Trastornos Parkinsonianos/diagnóstico por imagen , Trastornos Parkinsonianos/etiología , Linaje , Fosfoglicerato Quinasa/metabolismo , Radiofármacos , Sustancia Negra/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón Único , TropanosAsunto(s)
Encefalopatías/diagnóstico por imagen , Espectroscopía de Resonancia Magnética/métodos , Neoplasias Encefálicas/diagnóstico por imagen , Enfermedad de Canavan/diagnóstico por imagen , Humanos , Errores Innatos del Metabolismo/diagnóstico por imagen , Enfermedades Mitocondriales/diagnóstico por imagenRESUMEN
Dihydropyrimidinase deficiency is a rare autosomal recessive disease affecting the second step of pyrimidine degradation. It is caused by mutations in the DPYS gene. Only approximately 30 cases have been reported to date, with a phenotypical variability ranging from asymptomatic to severe neurological illness. We report a case of dihydropyrimidinase deficiency incidentally detected by urine metabolome analysis. Gas chromatography-mass spectrometry-based urine metabolomics demonstrated significant elevations of dihydrouracil and dihydrothymine, which were subsequently confirmed by a quantitative analysis using liquid chromatography-tandem mass spectrometry. Genetic testing of the DPYS gene revealed two mutations: a novel mutation (c.175Gâ¯>â¯T) and a previously reported mutation (c.1469Gâ¯>â¯A). Dihydropyrimidinase deficiency is probably underdiagnosed, considering its wide phenotypical variability, nonspecific neurological presentations, and an estimated prevalence of 2/20,000. As severe 5-fluorouracil-associated toxicity has been reported in patients and carriers of congenital pyrimidine metabolic disorders, urinary pyrimidine analysis should be considered for those who will undergo 5-fluorouracil treatment.
Asunto(s)
Errores Innatos del Metabolismo/complicaciones , Errores Innatos del Metabolismo/orina , Metaboloma , Errores Innatos del Metabolismo de la Purina-Pirimidina/complicaciones , Adolescente , Cromatografía Liquida , Humanos , Espectrometría de Masas , Errores Innatos del Metabolismo/diagnóstico por imagen , Calambre Muscular/etiología , Conducción Nerviosa , Errores Innatos del Metabolismo de la Purina-Pirimidina/diagnóstico por imagen , Errores Innatos del Metabolismo de la Purina-Pirimidina/orina , Pirimidinas/orinaRESUMEN
BACKGROUND: Continuous EEG studies demonstrate that neonates with seizures due to cerebral pathology, such as hypoxia ischemia, exhibit predominantly electrographic seizures (i.e. those only detected with EEG because they lack clinical features). Previous small case series demonstrate EEG changes and seizures during hyperammonemia associated with inborn errors of metabolism (IEM) but there are no reports utilizing continuous EEG in these conditions. OBJECTIVE: To characterize seizures and evaluate the utility of continuous EEG recording during hyperammonemia due to inborn errors of metabolism. METHODS: We retrospectively reviewed medical records and EEG tracings of neonates who presented with hyperammonemia due to inborn errors of metabolism who had continuous EEG and full medical records available for review, including follow up. RESULTS: Eight neonates with hyperammonemia were studied, 7 had urea cycle defects: Argininosuccinate lyase deficiency [3], (ornithine transcarbamylase deficiency [3], carbomyl phosphate synthase deficiency [1] and one had an organic acidemia: Methylmalonic acidemia [1]. Most common presentations were lethargy and poor feeding at 12-72â¯h of life. The highest blood ammonia level was 874⯵mol/L (median); range 823-1647⯵mol/L (normal value <50⯵mol/L in term neonates). Seven were treated with hemodialysis in addition to nitrogen scavengers. Seven neonates had seizures; six had only electrographic seizures. Seizures initially occurred within 24-36â¯h of clinical presentation, sometimes with normal ammonia and glutamine levels. Neonates with seizures all lacked state changes on EEG. Inter burst interval duration correlated with degree of hyperammonemia. Two cases with normal plasma ammonia but increasing interburst interval duration were proven to have stroke by MRI. CONCLUSIONS: Seizures occur frequently in neonates with hyperammonemia; most can be detected only with continuous EEG. Seizures may occur when ammonia and glutamine levels are normal. Interburst interval duration is associated with ammonia levels or cerebral dysfunction from other brain pathology. Continuous EEG can be a useful tool for managing infants with hyperammonemia and may be essential for seizure management especially for infants in deep metabolic coma.
Asunto(s)
Amoníaco/sangre , Electroencefalografía , Hiperamonemia/sangre , Errores Innatos del Metabolismo/sangre , Convulsiones/sangre , Errores Innatos del Metabolismo de los Aminoácidos/sangre , Errores Innatos del Metabolismo de los Aminoácidos/diagnóstico por imagen , Errores Innatos del Metabolismo de los Aminoácidos/fisiopatología , Argininosuccinato Sintasa/sangre , Aciduria Argininosuccínica/sangre , Aciduria Argininosuccínica/diagnóstico por imagen , Aciduria Argininosuccínica/fisiopatología , Femenino , Glutamina/sangre , Humanos , Hiperamonemia/diagnóstico por imagen , Hiperamonemia/fisiopatología , Hipoxia-Isquemia Encefálica/sangre , Hipoxia-Isquemia Encefálica/diagnóstico por imagen , Hipoxia-Isquemia Encefálica/fisiopatología , Lactante , Recién Nacido , Masculino , Errores Innatos del Metabolismo/diagnóstico por imagen , Errores Innatos del Metabolismo/fisiopatología , Enfermedad por Deficiencia de Ornitina Carbamoiltransferasa/sangre , Enfermedad por Deficiencia de Ornitina Carbamoiltransferasa/diagnóstico por imagen , Enfermedad por Deficiencia de Ornitina Carbamoiltransferasa/fisiopatología , Convulsiones/diagnóstico por imagen , Convulsiones/fisiopatologíaRESUMEN
Background: MEGDEL syndrome (3-MethylGlutaconic aciduria, Deafness, Encephalopathy, Leigh-like syndrome) is a severe neurometabolic disease with infantile onset. Phenomenology Shown: Progressive and marked dystonia over a 6-year period in an adult male with MEGDEL syndrome. Educational Value: Generalized dystonia may be the main manifestation of a milder form of MEGDEL syndrome, which begins during adulthood.
Asunto(s)
Encefalopatías/fisiopatología , Sordera/fisiopatología , Trastornos Distónicos/complicaciones , Enfermedad de Leigh/fisiopatología , Errores Innatos del Metabolismo/fisiopatología , Encéfalo/diagnóstico por imagen , Encefalopatías/diagnóstico por imagen , Sordera/diagnóstico por imagen , Progresión de la Enfermedad , Trastornos Distónicos/diagnóstico por imagen , Humanos , Enfermedad de Leigh/diagnóstico por imagen , Estudios Longitudinales , Masculino , Errores Innatos del Metabolismo/diagnóstico por imagenAsunto(s)
Enfermedades Cerebelosas/complicaciones , Enfermedades Cerebelosas/diagnóstico por imagen , Complejo III de Transporte de Electrones/deficiencia , Complejo II de Transporte de Electrones/deficiencia , Imagen por Resonancia Magnética , Errores Innatos del Metabolismo/complicaciones , Atrofia/diagnóstico por imagen , Preescolar , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Errores Innatos del Metabolismo/diagnóstico por imagenRESUMEN
BACKGROUND: Mitochondrial diseases, a group of multi-systemic disorders often characterized by tissue-specific phenotypes, are usually progressive and fatal disorders resulting from defects in oxidative phosphorylation. MTO1 (Mitochondrial tRNA Translation Optimization 1), an evolutionarily conserved protein expressed in high-energy demand tissues has been linked to human early-onset combined oxidative phosphorylation deficiency associated with hypertrophic cardiomyopathy, often referred to as combined oxidative phosphorylation deficiency-10 (COXPD10). MATERIAL AND METHODS: Thirty five cases of MTO1 deficiency were identified and reviewed through international collaboration. The cases of two female siblings, who presented at 1 and 2years of life with seizures, global developmental delay, hypotonia, elevated lactate and complex I and IV deficiency on muscle biopsy but without cardiomyopathy, are presented in detail. RESULTS: For the description of phenotypic features, the denominator varies as the literature was insufficient to allow for complete ascertainment of all data for the 35 cases. An extensive review of all known MTO1 deficiency cases revealed the most common features at presentation to be lactic acidosis (LA) (21/34; 62% cases) and hypertrophic cardiomyopathy (15/34; 44% cases). Eventually lactic acidosis and hypertrophic cardiomyopathy are described in 35/35 (100%) and 27/34 (79%) of patients with MTO1 deficiency, respectively; with global developmental delay/intellectual disability present in 28/29 (97%), feeding difficulties in 17/35 (49%), failure to thrive in 12/35 (34%), seizures in 12/35 (34%), optic atrophy in 11/21 (52%) and ataxia in 7/34 (21%). There are 19 different pathogenic MTO1 variants identified in these 35 cases: one splice-site, 3 frameshift and 15 missense variants. None have bi-allelic variants that completely inactivate MTO1; however, patients where one variant is truncating (i.e. frameshift) while the second one is a missense appear to have a more severe, even fatal, phenotype. These data suggest that complete loss of MTO1 is not viable. A ketogenic diet may have exerted a favourable effect on seizures in 2/5 patients. CONCLUSION: MTO1 deficiency is lethal in some but not all cases, and a genotype-phenotype relation is suggested. Aside from lactic acidosis and cardiomyopathy, developmental delay and other phenotypic features affecting multiple organ systems are often present in these patients, suggesting a broader spectrum than hitherto reported. The diagnosis should be suspected on clinical features and the presence of markers of mitochondrial dysfunction in body fluids, especially low residual complex I, III and IV activity in muscle. Molecular confirmation is required and targeted genomic testing may be the most efficient approach. Although subjective clinical improvement was observed in a small number of patients on therapies such as ketogenic diet and dichloroacetate, no evidence-based effective therapy exists.
Asunto(s)
Cardiomiopatía Hipertrófica/genética , Proteínas Portadoras/genética , Encefalopatía Hepática/genética , Errores Innatos del Metabolismo/genética , Enfermedades Mitocondriales/genética , Adolescente , Biopsia , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Cardiomiopatía Hipertrófica/diagnóstico por imagen , Cardiomiopatía Hipertrófica/fisiopatología , Proteínas Portadoras/metabolismo , Niño , Preescolar , Femenino , Mutación del Sistema de Lectura , Encefalopatía Hepática/diagnóstico por imagen , Encefalopatía Hepática/fisiopatología , Humanos , Lactante , Recién Nacido , Masculino , Errores Innatos del Metabolismo/diagnóstico por imagen , Errores Innatos del Metabolismo/fisiopatología , Enfermedades Mitocondriales/metabolismo , Enfermedades Mitocondriales/fisiopatología , Fosforilación Oxidativa , Proteínas de Unión al ARNAsunto(s)
Antiportadores de Cloruro-Bicarbonato/genética , Diarrea/congénito , Regulación del Desarrollo de la Expresión Génica , Errores Innatos del Metabolismo/diagnóstico por imagen , Errores Innatos del Metabolismo/terapia , Transportadores de Sulfato/genética , Ultrasonografía Prenatal/métodos , Adulto , Cesárea/métodos , Colon/anomalías , Colon/diagnóstico por imagen , Tratamiento Conservador , Diarrea/diagnóstico por imagen , Diarrea/genética , Diarrea/terapia , Dilatación , Femenino , Estudios de Seguimiento , Edad Gestacional , Humanos , Recién Nacido , Imagen por Resonancia Magnética/métodos , Errores Innatos del Metabolismo/genética , Embarazo , Resultado del Embarazo , Diagnóstico Prenatal/métodosAsunto(s)
Encefalopatías/genética , Encefalopatías/fisiopatología , Hidrolasas de Éster Carboxílico/genética , Errores Innatos del Metabolismo/genética , Errores Innatos del Metabolismo/fisiopatología , Mutación , Encéfalo/diagnóstico por imagen , Encéfalo/crecimiento & desarrollo , Encefalopatías/diagnóstico por imagen , Niño , Sordera/genética , Sordera/fisiopatología , Femenino , Humanos , Errores Innatos del Metabolismo/diagnóstico por imagen , Fenotipo , SíndromeRESUMEN
3-Methylglutaconic aciduria is a member of inborn errors of leucine metabolism pathway. 3-Methylglutaconic aciduria type I (MGA1) causes neurological problems which are present during infancy or childhood but the diagnosis may be delayed until adulthood. Here we report a 3years old patient with developmental delay from a relative parent's that his medical evaluations include analyses of urinary organic acid and blood acylcarnitine showed high level of 3-methylglutacoic acid, 3-hydroxyisovaleric acid and increased level of 3-hydroxyisovalerylcarnitine respectively. Further evaluation and genetic tests revealed a novel homozygous mutation of variant c.179del G (p.Gly60Valfs*12) in exon 1 of the AUH gene that was compatible with the diagnosis of MGA1. In segregation analysis of his family, both parents were heterozygous for the respective mutation, confirming obligate parental carrier status and segregation of the mutation.
Asunto(s)
Discapacidades del Desarrollo/genética , Enoil-CoA Hidratasa/genética , Errores Innatos del Metabolismo/genética , Mutación , Proteínas de Unión al ARN/genética , Encéfalo/diagnóstico por imagen , Preescolar , Discapacidades del Desarrollo/diagnóstico por imagen , Humanos , Masculino , Errores Innatos del Metabolismo/diagnóstico por imagenRESUMEN
Left ventricular hypertrophy (LVH) develops in response to a variety of physical, genetic, and biochemical stimuli and represents the early stage of ventricular remodeling. In patients with LVH, subclinical left ventricular (LV) dysfunction despite normal ejection fraction (EF) may be present before the onset of symptoms, which portends a dismal prognosis. Strain measurement with two-dimensional speckle tracking echocardiography (STE) represents a highly reproducible and accurate alternative to LVEF determination. The present review focuses on current available evidence that supports the incremental value of STE in the diagnostic and prognostic workup of LVH. When assessing the components of LV contraction, STE has an incremental value in differentiating between primary and secondary LVH and in the differential diagnosis with storage diseases. In addition, STE provides unique information for the stratification of patients with LVH, enabling to detect intrinsic myocardial dysfunction before LVEF reduction.