Elevated serum lactate dehydrogenase isoenzymes and aspartate transaminase distinguish Albers-Schönberg disease (Chloride Channel 7 Deficiency Osteopetrosis) among the sclerosing bone disorders

J Bone Miner Res. 2010 Nov;25(11):2515-26. doi: 10.1002/jbmr.130.

Abstract

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-Schönberg disease (A-SD)] among these conditions. Serum total LDH and AST levels as high as 3× and 2×, 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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aspartate Aminotransferases / blood*
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Chloride Channels / deficiency*
  • Chloride Channels / metabolism
  • Confidence Intervals
  • Creatine Kinase / blood
  • Diagnosis, Differential
  • Fatal Outcome
  • Female
  • Humans
  • Isoenzymes / blood
  • L-Lactate Dehydrogenase / blood*
  • Male
  • Organ Size
  • Osteopetrosis / blood
  • Osteopetrosis / diagnosis
  • Osteopetrosis / enzymology
  • Osteopetrosis / pathology
  • Osteosclerosis / blood*
  • Osteosclerosis / diagnosis
  • Osteosclerosis / enzymology*
  • Osteosclerosis / pathology
  • Reference Values

Substances

  • CLCN7 protein, human
  • Chloride Channels
  • Isoenzymes
  • L-Lactate Dehydrogenase
  • Aspartate Aminotransferases
  • Creatine Kinase