title: Hypoalbuminemia in early onset dentatorubral-pallidoluysian atrophy due to leakage of albumin in multiple organs.
abstract: We delineate a complication of hypoalbuminemia in dentatorubral-pallidoluysian atrophy (DRPLA), which we have found to be common in this disorder. In addition, we explored the pathogenesis of this phenomenon through clinical and histological examinations. Clinical course and laboratory findings of nine patients with childhood-onset DRPLA (aged 6-49 years; CAG repeat length 62-93) were retrospectively reviewed. Autopsied specimens from three patients were examined by histopathological and immunohistochemical analyses. Eight DRPLA patients showed hypoalbuminemia <3.5 g/dl in the initial stages of the disease (age, 2-32 years), which correlated with the CAG repeat length in each patient. Disease worsened in six patients, often triggered by febrile infections and accompanied by increased urinary protein excretion. One patient showed increased fecal α1-antitripsin while another showed accumulation of radioactive albumin in the urinary and gastrointestinal tracts after intravenous infusion. Immunohistochemistry revealed albumin-containing monocytes and astrocytes in the perivascular areas of the cerebral white matter. Fluid collection in the glomerular capillaries was noted. Immunolabeling using antibodies against the expanded polyglutamine (polyQ) polypeptide was positive in cerebral cortical neurons, hepatocytes, renal collecting ducts, and glomerular podocytes, which act as filtration barrier against serum proteins. Serum albumin appears to easily leak from blood vessels in certain visceral organs in DRPLA during later stages of the illness, particularly in the kidneys of patients with largely expanded CAG repeats. We hypothesize that the accumulation of the DRPLA gene product with expanded polyQ sequences in the podocytes results in the dysfunction of the glomerular filtration barrier.
authors.affiliation: Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan.
authors.forename: Shigehiro
authors.initials: S
authors.lastname: Nagai
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Saito
authors.forename: Yukari
authors.initials: Y
authors.lastname: Endo
authors.forename: Takashi
authors.initials: T
authors.lastname: Saito
authors.forename: Kenji
authors.initials: K
authors.lastname: Sugai
authors.forename: Akihiko
authors.initials: A
authors.lastname: Ishiyama
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Komaki
authors.forename: Eiji
authors.initials: E
authors.lastname: Nakagawa
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sasaki
authors.forename: Kimiteru
authors.initials: K
authors.lastname: Ito
authors.forename: Yuko
authors.initials: Y
authors.lastname: Saito
authors.forename: Sayuri
authors.initials: S
authors.lastname: Sukigara
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ito
authors.forename: Yu-Ichi
authors.initials: Y
authors.lastname: Goto
authors.forename: Shuichi
authors.initials: S
authors.lastname: Ito
authors.forename: Kentaro
authors.initials: K
authors.lastname: Matsuoka
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D041981:Gastrointestinal Tract / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D034141:Hypoalbuminemia / Q000209:etiology* / Q000235:genetics*; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology; D008099:Liver / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D020191:Myoclonic Epilepsies, Progressive / Q000150:complications / Q000235:genetics / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics; D010455:Peptides / Q000378:metabolism; D011877:Radionuclide Imaging; D012709:Serum Albumin / Q000378:metabolism*; D013223:Statistics as Topic; D019680:Trinucleotide Repeat Expansion / Q000235:genetics; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D009419:Nerve Tissue Proteins; D010455:Peptides; D012709:Serum Albumin; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C095278:atrophin-1; C097188:polyglutamine