1.
Neonatal mitochondrial leukoencephalopathy with brain and spinal involvement and high lactate: expanding the phenotype of ISCA2 gene mutations.
Toldo, I, Nosadini, M, Boscardin, C, Talenti, G, Manara, R, Lamantea, E, Legati, A, Ghezzi, D, Perilongo, G, Sartori, S
Metabolic brain disease. 2018;(3):805-812
Abstract
A homoallelic missense founder mutation of the iron-sulfur cluster assembly 2 (ISCA2) gene has been recently reported in six cases affected by an autosomal recessive infantile neurodegenerative mitochondrial disorder. We documented a case of a 2-month-old girl presenting with severe hypotonia and nystagmus, who rapidly deteriorated and died at the age of three months. Increased cerebral spinal fluid level of lactate, documented also at the brain spectroscopy, involvement of the cortex, restricted diffusion of white and gray matter abnormalities, sparing of the corpus callosum and extensive involvement of the spinal cord were observed. Her clinical presenting features and course as well as some neuroradiological findings mimicked those of early-onset leukoencephalopathy with brainstem and spinal cord involvement and high brain lactate (LBSL). The analysis of the mitochondrial respiratory chain function showed a reduced activity of complexes II and IV. The girl harboured two heterozygous mutations in the ISCA2 gene. A comprehensive review of the literature and a comparison with the cases of early onset LBSL enabled us to highlight significant differences in the clinical, biochemical and neuroradiological phenotype between the two conditions, which also emerged from the comparison with the other 6 reported cases of ISCA2 gene mutation previously reported. In summary, this represents the second report ever published associating ISCA2 gene mutation with a mitochondrial leukoencephalopathy, with a different genetic mechanism to the previous cases. Molecular analysis of ISCA2 should be included in the genetic panel for the diagnosis of early onset mitochondrial leukoencephalopathies.
2.
Intestinal Microbial and Metabolic Alterations Following Successful Fecal Microbiota Transplant for D-Lactic Acidosis.
Bulik-Sullivan, EC, Roy, S, Elliott, RJ, Kassam, Z, Lichtman, SN, Carroll, IM, Gulati, AS
Journal of pediatric gastroenterology and nutrition. 2018;(4):483-487
Abstract
Fecal microbiota transplantation (FMT) involves the transfer of stool from a healthy individual into the intestinal tract of a diseased recipient. Although used primarily for recurrent Clostridium difficile infection, FMT is increasingly being attempted as an experimental therapy for other illnesses, including metabolic disorders. D-lactic acidosis (D-LA) is a metabolic disorder that may occur in individuals with short bowel syndrome when lactate-producing bacteria in the colon overproduce D-lactate. This results in elevated systemic levels of D-lactate, metabolic acidosis, and encephalopathy. In this study, we report the successful use of FMT for the treatment of recurrent D-LA in a child who was unresponsive to conventional therapies. Importantly, we also present profiles of the enteric microbiota, as well as fecal D-/L-lactic acid metabolites, before and longitudinally after FMT. These data provide valuable insight into the putative mechanisms of D-LA pathogenesis and its treatment.
3.
Proton MR spectroscopy reveals lactate in infantile neuroaxonal dystrophy (INAD).
Mader, I, Krägeloh-Mann, I, Seeger, U, Bornemann, A, Nägele, T, Küker, W, Grodd, W
Neuropediatrics. 2001;(2):97-100
Abstract
Changes of cerebral metabolites detected by proton MR spectroscopy in two cases of infantile neuroaxonal dystrophy are described. A 6 11/12-year-old boy and a girl (aged 4 1/12 years at the first and 5 2/12 years at the second examination) with infantile neuroaxonal dystrophy were investigated by magnetic resonance imaging and spectroscopy of the basal ganglia. The signal intensity of the cerebellar cortex was increased on T2-weighted, proton density, and fluid attenuated inversion recovery images. The long echo time (135 ms) spectra revealed the presence of lactate in the basal ganglia of both cases in all investigations. The N-acetylaspartate/creatine ratio was reduced in Case 1 and in the second investigation of Case 2. The choline/creatine ratio was always increased. As the diagnosis of infantile neuroaxonal dystrophy is made by a synopsis of various clinical, neuropathological, neurophysiological, and neuroradiological data, the presence of lactate in the basal ganglia spectra may help to narrow down the diagnosis and can support the decision to perform more invasive diagnostic procedures (such as biopsies of skin, conjunctiva or even of the brain).