{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T21:10:26Z","timestamp":1774645826999,"version":"3.50.1"},"reference-count":59,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2010,5,17]],"date-time":"2010-05-17T00:00:00Z","timestamp":1274054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Osteopetrosis (OPT) refers to the consequences of generalized failure of skeletal resorption during growth. Most cases are explained by loss-of-function mutation within the genes that encode either chloride channel 7 (CLCN7) or a vacuolar proton pump subunit (TCIRG1), each compromising acid secretion by osteoclasts. Patients suffer fractures and sometimes cranial nerve entrapment and insufficient medullary space for hematopoiesis. In 1996, we reported that a high serum level of the brain isoenzyme of creatine kinase (BB-CK), the CK of osteoclasts, characterizes OPT dueamong the sclerosing bone disorders (J Clin Endocrinol Metab. 1996;11:1438). Now, we show that elevation in serum of multiple lactate dehydrogenase (LDH) isoenzymes with aspartate transaminase (AST) distinguishes autosomal dominant OPT due to loss-of-function mutation in CLCN7 [Albers-Sch\u00f6nberg disease (A-SD)] among these conditions. Serum total LDH and AST levels as high as 3\u00d7 and 2\u00d7, respectively, the upper limits of normal for age-appropriate controls, were persistent and essentially concordant in A-SD. Serum LDH was elevated in 7 of 9 children and in the 2 adults studied with A-SD. LDH isoenzyme quantitation showed excesses of LDH-2, -3, and -4. Neither total LDH nor AST increases were found in other forms of OPT, including bisphosphonate-induced OPT, or in 41 children and 6 adults representing 20 additional sclerosing bone disorders. Serum TRACP-5b and BB-CK also were markedly elevated in A-SD. Hence, high serum levels of several enzymes characterize A-SD. Elevated serum LDH isoenzymes and AST indicate a disturbance (of uncertain clinical significance) within multiple extraosseous tissues when there is CLCN7 deficiency. \u00a9 2010 American Society for Bone and Mineral Research.<\/jats:p>","DOI":"10.1002\/jbmr.130","type":"journal-article","created":{"date-parts":[[2010,5,17]],"date-time":"2010-05-17T18:08:56Z","timestamp":1274119736000},"page":"2515-2526","source":"Crossref","is-referenced-by-count":41,"title":["Elevated serum lactate dehydrogenase isoenzymes and aspartate transaminase distinguish Albers-Sch\u00f6nberg disease (Chloride Channel 7 Deficiency Osteopetrosis) among the sclerosing bone disorders"],"prefix":"10.1093","volume":"25","author":[{"given":"Michael P","family":"Whyte","sequence":"first","affiliation":[{"name":"Division of Bone and Mineral Diseases, Washington University School of Medicine at Barnes-Jewish Hospital, St Louis, MO, USA"},{"name":"Center for Metabolic Bone Disease and Molecular Research, Shriners 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