Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acquired Fanconi syndrome (FS) is a complication of monoclonal gammopathies featuring a generalized dysfunction of the proximal tubule of the kidney, due to the storage within proximal tubular cells of a monoclonal immunoglobulin light chain. We engineered transgenic mice in which the endogenous mouse Jkappa cluster was replaced by a human VkappaJkappa rearranged gene cloned from a patient with smoldering myeloma-associated FS. The V region belonged to the VkappaI subgroup and was related to the O2-O12 germ-line gene, a V segment previously found associated with FS and light-chain crystallization in several patients with myeloma. Association of the human VkappaI domain with a mouse kappa constant domain in transgenic animals yielded a nephrotoxicity pattern similar to that observed in patients, strongly suggesting that the whole pathogenic effect of FS light chains can be ascribed to a peculiar structure of the V domain. Morphologic alterations of the kidney tubular cells, which contained rhomboid-shape crystals, were observed in mice, together with alterations of the proximal tubule reabsorption function. Moreover, the number of renal crystalline inclusions was dramatically reduced after conditional deletion of the human VkappaI transgene, showing that proximal tubular lesions are reversible upon suppression of the nephrotoxic light chain secretion.
 ...
PMID:Role of the monoclonal kappa chain V domain and reversibility of renal damage in a transgenic model of acquired Fanconi syndrome. 1654 71

Acquired Fanconi syndrome (FS) is a rare presentation of monoclonal gammopathy. We retrospectively summarized the cases of eight patients with FS secondary to monoclonal gammopathy at Peking Union Medical College Hospital (PUMCH) from January 2007 to April 2014. All patients had generalized or partial impairment of proximal renal tubular function. Six patients were diagnosed with monoclonal gammopathy of undetermined significance (MGUS), and two were diagnosed with multiple myeloma (MM). Although chemotherapy was administered to the two patients with MM and to one patient with MGUS, decreased paraprotein levels did not lead to improvements in metabolic abnormalities. All patients received continuous supplementation with deficient nutrients, leading to marked remission of bone pain and improved quality of life. Although renal function in most patients gradually declined, none of the patients developed end-stage renal disease (ESRD) during an average follow-up time of 31 months, and no case of MGUS has yet transformed into MM.
...
PMID:A single-center case series of eight patients with the rare plasma cell dyscrasia of acquired Fanconi syndrome secondary to monoclonal gammopathy. 2579 Dec 36