1/3. magnetic resonance imaging of the brain in glutaric acidemia type I: a review of the literature and a report of four new cases with attention to the basal ganglia and imaging technique.RATIONALE AND OBJECTIVES: In glutaric acidemia type I (GA I), a pediatric neurometabolic disease that may be mistaken for nonaccidental trauma, expeditious detection is critical as early treatment may substantially improve psychomotor dysfunction. In this study, we examine in depth the magnetic resonance (MR) findings, with special attention to the basal ganglia, in 4 new cases and compare the findings with those described in the literature. methods: MR studies of 4 children, diagnosed to have GA I via cultured fibroblast enzyme studies or urine metabolite assays, were performed on a 1.5 T system in the axial plane using spin echo T(1)-weighted, fast spin echo T(2)-weighted, and fluid-attenuated inversion recovery (FLAIR) technique. Three of 4 patients were followed with serial exams to document temporal evolution of the disease. RESULTS: On T(2)-weighted images, abnormal increased signal intensity was seen in both the putamen and globus pallidus in all cases. However, in contradistinction to cases reported in the literature, involvement of the caudate nucleus was minimal or absent even on serial MR exams. In children 15 months and older, FLAIR improved recognition of basal ganglia and white matter abnormalities. The previously described widened cerebrospinal fluid spaces anterior to the temporal lobes, increased T(2)-weighted signal intensity in the periventricular white matter, and widened sylvian fissures characteristic of GA I were noted in all patients. CONCLUSIONS: Abnormalities of the caudate nucleus are not a prominent presentation of these patients and the absence of this finding should not exclude a diagnosis of GA I. FLAIR scans, as an adjunct to more conventional T(1)- and T(2)-weighted sequences, can play an important role in children 15 months or older despite immature myelination in these patients.- - - - - - - - - - ranking = 1keywords = nucleus (Clic here for more details about this article) |
2/3. Variable penetrance of a familial progressive necrotising encephalopathy due to a novel tRNA(Ile) homoplasmic mutation in the mitochondrial genome.INTRODUCTION: We present a family comprising a clinically normal mother and two daughters, each with severe encephalopathy with onset in late childhood. A third daughter had died previously of an earlier onset but neuropathologically similar disease. methods: sequence analysis of the entire mtDNA was carried out in muscle, fibroblasts, and lymphocytes of the affected daughters and unaffected mother. Biochemical analysis of individual respiratory chain enzymes was performed on the same tissues, and on several transmitochondrial cybrid clones containing the nucleus of a 143B.206 osteosarcoma cell line and the mutant mtDNA. RESULTS: Genetic analyses revealed in both daughters and mother the presence of a novel mutation in the tRNA(Ile) gene of mtDNA, which was homoplasmic in fibroblasts, lymphocytes, and skeletal muscle of the two patients. It was also homoplasmic in fibroblast and skeletal muscle samples of the mother, and approximately 97% heteroplasmic in her lymphocytes. Combined defects of complexes I and IV of the mitochondrial respiratory chain were found not only in fibroblasts of the two probands, but surprisingly also in those of their clinically unaffected mother. The respiratory chain defect segregated in transmitochondrial cybrids containing the nucleus of a 143B.206 osteosarcoma cell line and the mutant mtDNA, indicating that the latter was responsible for the biochemical phenotype. DISCUSSION: Our results support the concept that homoplasmic mutations in tRNA genes can be responsible for mitochondrial disorders characterised by extremely variable penetrance. Albeit still unexplained, this phenomenon has important consequences in the nosological characterisation, clinical management, and genetic counselling of mitochondrial disorders.- - - - - - - - - - ranking = 1keywords = nucleus (Clic here for more details about this article) |
3/3. L-2-hydroxyglutaric aciduria: clinical, neuroimaging, and neuropathological findings.BACKGROUND: l-2-Hydroxyglutaric aciduria is a rare, infantile-onset, autosomal recessive organic aciduria affecting exclusively the central nervous system. To our knowledge, only 1 complete report of the neuropathological findings in an adult has been published. OBJECTIVE: To present the clinical, neuroimaging, and neuropathological findings of l-2-hydroxyglutaric aciduria. DESIGN: Case report. SETTING: Complexo Hospitalario de Pontevedra, Pontevedra, spain. PATIENT: A 15-year-old boy who had early infantile-onset progressive psychomotor regression, mild choreodystonia affecting the distal part of the upper limbs, pyramidal signs, and epilepsy. RESULTS: The diagnosis of l-2-hydroxyglutaric aciduria was confirmed by the finding of highly elevated levels of l-2-hydroxyglutaric acid in the serum, urine, and cerebrospinal fluid. The neuroimaging findings showed striking confluent subcortical white matter lesions and minimal basal ganglia (pallidum, thalamic, and putaminal) abnormalities. The patient died of a spontaneous mesenteric thrombosis. The postmortem neuropathological findings showed spongiosis and cystic cavitations in subcortical white matter, with minimal abnormalities of the basal ganglia. The dentate nucleus, a structure usually affected in neuroimaging studies, showed minimal neuronal loss but was surrounded by important spongiosis and microvacuolation with astrocytic proliferation. CONCLUSIONS: This case reaffirms that l-2-hydroxyglutaric aciduria is a spongiform type of leukoencephalopathy with cystic cavitations predominating in the subcortical areas. Although the neuroimaging findings are highly characteristic of the disease, in this patient cerebellar abnormalities were minimal and dentate signal abnormalities were not present.- - - - - - - - - - ranking = 0.5keywords = nucleus (Clic here for more details about this article) |