Mutations in MCT1 cDNA in patients with symptomatic deficiency in lactate transport

We identified 5 patients with subnormal erythrocyte lactate transport plus symptoms and signs of muscle injury on exercise and heat exposure. All had transport rates below the 95% envelope for normals. Three cases had rates 40–50% of mean normal. One was found to have a missense mutation in monocarb...

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Bibliographic Details
Published in:Muscle & nerve 2000-01, Vol.23 (1), p.90-97
Main Authors: Merezhinskaya, Natalya, Fishbein, William N., Davis, John I., Foellmer, John W.
Format: Article
Language:English
Subjects:
Adult
Arm - blood supply
Biological and medical sciences
Biological Transport, Active - genetics
Carbohydrate Metabolism, Inborn Errors - genetics
Carrier Proteins - genetics
creatine kinase
Diseases of striated muscles. Neuromuscular diseases
DNA, Complementary - genetics
Electrophoresis, Agar Gel
Erythrocytes - metabolism
Humans
lactate transport
Lactic Acid - metabolism
Male
MCT1 mutations
Medical sciences
Middle Aged
Monocarboxylic Acid Transporters
muscle cramping
Muscle, Skeletal - chemistry
Mutation - genetics
Neurology
Polymorphism, Single-Stranded Conformational
Regional Blood Flow - physiology
Reverse Transcriptase Polymerase Chain Reaction
rhabdomyolysis
RNA, Messenger - biosynthesis
RNA, Messenger - genetics
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Summary:We identified 5 patients with subnormal erythrocyte lactate transport plus symptoms and signs of muscle injury on exercise and heat exposure. All had transport rates below the 95% envelope for normals. Three cases had rates 40–50% of mean normal. One was found to have a missense mutation in monocarboxylate transporter 1 (MCT1), the gene for the red cell lactate transporter (also expressed in skeletal muscle), at a conserved site, which was not mutated in a cohort of 90 normal humans. The other 2 cases had a different missense mutation (at a nonconserved site), which was also not mutated in the normal cohort. All 3 patients were heterozygotes. We presume that these mutations are responsible for their subnormal lactate transport, and hence their muscle injury under environmental stress; homozygous patients should be more seriously compromised. The other 2 cases had lactate transport rates 60–65% of mean normal, and their MCT1 revealed a third mutation, which proved to be a common polymorphism in the normal cohort. These 2 patients may be physiologic outliers in lactate transport, with their muscle damage arising from some other genetic defect. © 2000 John Wiley & Sons, Inc. Muscle Nerve 23: 90–97, 2000
ISSN:0148-639X
1097-4598
DOI:10.1002/(SICI)1097-4598(200001)23:1<90::AID-MUS12>3.0.CO;2-M