Biomedical subjects
Y Campos
Publications and source records attributed to Y Campos.
[Early mitochondrial encephalomyopathy due to complex IV deficiency consistent with Alpers-Huttenlocher syndrome: report of two cases].
INTRODUCTION: Complex IV or cytochrome c oxidase (COX) deficiency is the most common disorder involving complexes of the respiratory chain in the pediatric age. Exceptionally, it has been reported in association with Alpers syndrome or Alpers disease, and with its variant named progressive neuronal degeneration with liver disease or Alpers-Huttenlocher syndrome. OBJECTIVE: To report the cases of two infants with mitochondrial encephalomyopathy due to COX deficiency in whom the clinical, biochemical, neurophysiologic and neuroimaging characterization suggested an associated Alpers-Huttenlocher syndrome. CLINICAL CASES: Two no-related males, one with noncontributory family history and the other with third-grade consanguineous parents developed refractory seizures from age 20 and 60 days, respectively. Additionally, myoclonic fits accounted on evolution of the condition. In the first case, serial EEG recordings showed low amplitude polyspikes, polyspike waves and very slow waves of high amplitude alternating with a trace of burst-suppression activity. In the second case, a right preponderant but also bilateral low amplitude polyspikes, polyspike waves and occasional desynchronization of basal trace were recorded. In both, a rapidly progressive cerebral atrophy, neurological deterioration with pyramidal signs, and tendency to microcephaly, ensued. Accompanying to this clinical picture, minor hepatic dysfunction, elevated protein levels in the CSF, lactic acidosis and COX deficiency in muscle homogenate were demonstrated. In the first case, moreover, cortical blindness and severe hepatic failure occurred while receiving valproate, in spite of concomitant L-carnitine therapy. CONCLUSIONS: We believe that the reported cases are consisted with Alpers-Huttenlocher syndrome associated with mitochondrial encephalomyopathy due to COX deficiency. Nevertheless, early myoclonic encephalopathy, a condition related in same cases with poliodistrophy, must be keep in mind as a possible diagnosis in case 1.
[Mitochondrial encephalopathies].
OBJECTIVE: We carry out a review of the current basic genetic, biochemical, clinical, diagnostic and therapeutic aspects of mitochondrial cytopathies due to deficiencies in the mitochondrial respiratory chain complexes, which appear clinically during childhood and/or adolescence. DEVELOPMENT: The clinical description has been divided into two groups: mitochondrial cytopathies secondary to alterations of mitochondrial DNA (mtDNA) and mitochondrial cytopathies secondary to alterations of the nuclear DNA (nDNA); we also consider about the importance of such conditions at this age.
[Benign congenital myopathy associated with a partial deficiency of complexes I and III of the mitochondrial respiratory chain]].
INTRODUCTION: Isolated or combined enzyme deficiencies of the mitochondrial respiratory chain results in a number of clinical heterogeneous conditions. When presented in the neonatal period or early in the infancy the course is usually severe, although isolated cases with benign evolution have also been described. OBJECTIVE: To describe the clinical and biochemical characteristics of a child with a benign form of mitochondrial myopathy due to a combined deficiency of the complexes I and III of the respiratory chain. CLINICAL CASE: A 40 days-old male, the second son of a young non-consanguineous couple, presented with axial congenital hypotonia, asymmetrical macrocephaly, mild enlargement of the liver, mild coarsening of facial features, increased CK serum values, persistently elevation of serum lactate and lactate/pyruvate ratio and external hydrocephalus. Electromyogram and histological muscle examination were normal but analysis of the respiratory chain disclosed a deficiency of the complexes I and III. From 13 months-age onwards clinical detailed abnormalities progressively ameliorated and also did it serum CK, lactate and external hydrocephalus. CONCLUSION: We think that on clinical, basic biochemical and histological grounds there are some similarities between this case of congenital unspecific myopathy and benign reversible form of mitochondrial myopathy, arguing in favor of a possible relationship between both conditions.
[Multiple symmetrical lipomatosis with familial polineuropathy].
INTRODUCTION: Multiple symmetrical lipomatosis (LSM) is characterized by the development of symmetrical lipomas and is often associated with axonal polyneuropathy (PNP). Presentation is usually sporadic. Familial cases have been reported infrequently, with variable modes of inheritance. The pathogenesis is unknown. It has been related to mitochondrial cytopathy and alterations in lipid metabolism. OBJECTIVES: To establish clinico pathological correlation in our cases of familial presentation. Patients and methods. We report seven patients, from three families, teetotalers with LSM. Clinical assessment included lipidogram, neurophysiological study of nerve and muscle, sural nerve biopsy in two of them and muscle biopsy in one member of each family for morphological assessment, respiratory chain biochemistry and study of molecular genetics. RESULTS: LSM was associated with axonal PNP and hyperlipidemia in the seven members of the three families, with an apparent pattern of autosomal recessive inheritance. No conclusive data of mitochondrial cytopathy, in the form of significant morphological changes, biochemistry of the mitochondrial respiratory chain or micochondrial DNA were found. CONCLUSION: Although mitochondrial cytopathy has been described as part of the syndromes in which LSM occurs, there may be other undefined aspects, such as disorders of lipid metabolism which form part of the pathogenesis.
[MELAS syndrome masquerading as herpes encephalitis: genetic diagnosis].
INTRODUCTION: MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke like episodes) is a mitochondrial disease related to the mitochondrial DNA mutation. The tRNALeu(UUR) mutation at the base pair 3234 is associated to 80% of cases of MELAS syndrome. The onset with the stroke like episodes is often before the age 40. Herpes simplex encephalitis (HSE) presents as acute episodes of focal neurologic deficit that are often related to the temporal lobe. Occasionally MELAS syndrome and HSE may have a similar clinical presentation. CLINICAL CASE: A 33-year-old woman presented with seizures and a right parietotemporal syndrome of acute onset. The differential diagnosis between HSE and MELAS syndrome was established. MELAS syndrome was suspected based on her phenotype. The diagnosis of MELAS syndrome was confirmed by the presence of the mitochondrial tRNALeu(UUR) mutation at the base pair 3243. CONCLUSION: The clinical presentation of the MELAS syndrome may mimic that of the HSE, and antiviral treatment should be given until the diagnosis of MELAS syndrome is definitive. The study of the mitochondrial DNA helps diagnosing in a non invasive way many patients with MELAS syndrome.
[Molecular genetics of disorders of the mitochondrial respiratory chain].
Mitochondria have a key role in cell metabolism, being the major site of ATP production via oxidative phosphorylation. This system consists of five multiprotein complexes, whose individuals subunits are encoded either by the mitochondrial or by the nuclear genome. Respiratory chain enzyme deficiencies result in devastating, usually multisystem, disorders. Recently, many underlying mutations in mitochondrial and nuclear genes have been described at a brisk pace as a result of the advances in the knowledge of molecular genetics.
[Multiple symmetric lipomatosis associated to polyneuropathology, atrophy of the cerebellum and mitochondrial cytopathy].
INTRODUCTION: Multiple symmetric lipomatosis (MSL), which is predominantly found in middle aged males, is characterised by accumulations of fat in the neck, shoulders and other parts of the trunk, and sometimes associated with different neurological manifestations, both central and peripheral. Although its aetiology is unknown, it has been described as associated with mitochondrial cytopathies. AIMS. To describe the case of a young female with MSL associated with mitochondrial encephalomyopathy. CASE REPORT: Girl aged 14 with MSL, ataxia, patellar hyperreflexia, bilateral Babinski sign, pes cavus, axonal peripheral neuropathy, involvement of the optic pathway, atrophy of the cerebellum, subsarcolemmal mitochondrial accumulations in the untrastructural examination of the vastus lateralis muscle and partial deficit of complex I in the mitochondrial respiratory chain. As regards molecular genetic aspects, the most frequent mutations of the ATPase 6 gene in lymphocytes, and mtDNA deletions and tRNALys and tRNALeu(UUR) mutations in muscles were excluded. CONCLUSIONS: Despite the fact that MSL is an entity normally found in adults, the possibility of its being diagnosed in the paediatric age must be taken into account. This case is probably the second time MSL has been observed associated with mitochondrial cytopathy in this age bracket.
Single fiber electromyography (SFEMG) in mitochondrial diseases (MD).
Conventional EMG, nerve conduction studies and SFEMG were performed in 18 patients with various phenotypes of MD. 14 cases showed findings consistent with mild myopathy, 2 patients signs of sensory-motor axonal neuropathy and 2 cases a mixture of myopathy and axonal neuropathy. Motor unit fiber density was mild increased in 8 out of 13 tested cases. Jitter was abnormal in 10 out of 18 tested patients. Jitter abnormalities were not related to myopathic or neurogenic features in the EMG study, and may be observed in muscles without clinical weakness. The results suggest the existence of neuromuscular transmission disturbances in patients with MD.
[Complex I and IV deficits in the mitochondrial respiratory chain in two siblings with type I glutaric aciduria].
We report two brothers with a glutaric aciduria type I (GA-I) identified by Glutaryl-coenzyme A dehydrogenase deficiency in skin fibroblasts. The onset of neurologic abnormalities was at 6 and 9 months of age as an acute Reye-like presentation in one. Because of the hyperlactacidemia, hyperlactatorrachia, mitochondrial abnormalities in muscular cells and a deficiency in complex I and IV of the respiratory chain in isolated mitochondria from muscle, a presumptive diagnosis of Leigh syndrome was made. We analyze the difference between both disorders. GA-I should be suspected in patients with acute dystonia and psychomotor regression, lactic acidosis and hypodensity of the basal ganglia.