Subscribe to RSS
DOI: 10.1055/s-0040-1705172
Autopsy Report of a Woman with Infantile Alexander Disease Who Survived 39 Years
Publication History
26 August 2019
04 February 2020
Publication Date:
06 March 2020 (online)
Abstract
Patients with infantile Alexander disease (AxD) usually do not survive beyond their early teens without life support care because of progressive central hypoventilation. We present the autopsy report of a woman with infantile AxD carrying an R239C mutation in the glial fibrillary acidic protein gene, who survived 39 years. She presented with psychomotor retardation in infancy and regressed after age 5. Brain computed tomography scans showed bilateral low frontal white matter density. She became quadriplegic with bulbar palsy and was intellectually handicapped after a measles infection at age 7. Tube feeding was introduced because of dysphagia at age 15. Noninvasive positive pressure ventilation was required due to central hypoventilation in her early thirties. She died of neurogenic respiratory failure at 39 years. Autopsy findings revealed a markedly atrophic brain (709 g, −6.0 standard deviation), especially in the frontal lobe, cerebellum, and brainstem portions. We found demyelination, gliosis, and cystic lesions throughout the brain, and we saw Rosenthal fibers accumulating in the perivascular spaces. We also identified a variety of abnormalities in other organs such as pancreatic necrosis, completely desquamated epithelium in the lower esophagus and stomach, foreign-body giant cells in the colon submucosa, glomerular sclerosis, and multiple bladder stones. This is the first autopsied case report of a patient with infantile AxD with long survival, who showed not only central nervous system characteristic findings, but also unexpected pathological changes in other organs.
Note
Location where the work was performed: Institution for Children with Profound Multiple Disabilities, Kanagawa Children's Medical Center.
-
References
- 1 Brenner M, Johnson AB, Boespflug-Tanguy O, Rodriguez D, Goldman JE, Messing A. Mutations in GFAP, encoding glial fibrillary acidic protein, are associated with Alexander disease. Nat Genet 2001; 27 (01) 117-120
- 2 Shiihara T, Yoneda T, Mizuta I, Yoshida T, Nakagawa M, Shimizu N. Serial MRI changes in a patient with infantile Alexander disease and prolonged survival. Brain Dev 2011; 33 (07) 604-607
- 3 Li R, Johnson AB, Salomons G. , et al. Glial fibrillary acidic protein mutations in infantile, juvenile, and adult forms of Alexander disease. Ann Neurol 2005; 57 (03) 310-326
- 4 Wakabayashi K, Lai M, Masuko K. , et al. A case of long-term survival of a patient with infantile Alexander disease diagnosed by DNA analysis [in Japanese]. No To Hattatsu 2005; 37 (01) 55-59
- 5 Rodriguez D, Gauthier F, Bertini E. , et al. Infantile Alexander disease: spectrum of GFAP mutations and genotype-phenotype correlation. Am J Hum Genet 2001; 69 (05) 1134-1140
- 6 van der Knaap MS, Pronk JC, Scheper GC. Vanishing white matter disease. Lancet Neurol 2006; 5 (05) 413-423
- 7 Tian R, Wu X, Hagemann TL. , et al. Alexander disease mutant glial fibrillary acidic protein compromises glutamate transport in astrocytes. J Neuropathol Exp Neurol 2010; 69 (04) 335-345
- 8 Tamasaki A, Nishimura Y, Kondo N, Shirai K, Maegaki Y, Ohno K. Risk factors for acute pancreatitis in patients with severe motor and intellectual disabilities. Pediatr Int 2014; 56 (02) 240-243
- 9 Gnessin E, Mandeville JA, Handa SE, Lingeman JE. Changing composition of renal calculi in patients with musculoskeletal anomalies. J Endourol 2011; 25 (09) 1519-1523
- 10 Morris LG, Stephenson KE, Herring S, Marti JL. Recurrent acute pancreatitis in anorexia and bulimia. JOP 2004; 5 (04) 231-234
- 11 Wesson RN, Sparaco A, Smith MD. Chronic pancreatitis in a patient with malnutrition due to anorexia nervosa. JOP 2008; 9 (03) 327-331
- 12 Sandhyamani S, Vijayakumari A, Balaraman Nair M. Bonnet monkey model for pancreatic changes in induced malnutrition. Pancreas 1999; 18 (01) 84-95
- 13 Kim J, Sun Z, Ezekian B. , et al. Gallbladder abnormalities in children with metachromatic leukodystrophy. J Surg Res 2017; 208: 187-191
- 14 Kemp S, Huffnagel IC, Linthorst GE, Wanders RJ, Engelen M. Adrenoleukodystrophy—neuroendocrine pathogenesis and redefinition of natural history. Nat Rev Endocrinol 2016; 12 (10) 606-615
- 15 Clairembault T, Kamphuis W, Leclair-Visonneau L. , et al. Enteric GFAP expression and phosphorylation in Parkinson's disease. J Neurochem 2014; 130 (06) 805-815