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Previous Volume 361:489-495 July 30, 2009 Number 5 Next

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SUMMARY

The mitochondrial aspartate–glutamate carrier isoform 1 (AGC1), specific to neurons and muscle, supplies aspartate to the cytosol and, as a component of the malate–aspartate shuttle, enables mitochondrial oxidation of cytosolic NADH, thought to be important in providing energy for neurons in the central nervous system. We describe AGC1 deficiency, a novel syndrome characterized by arrested psychomotor development, hypotonia, and seizures in a child with a homozygous missense mutation in the solute carrier family 25, member 12, gene SLC25A12, which encodes the AGC1 protein. Functional analysis of the mutant AGC1 protein showed abolished activity. The child had global hypomyelination in the cerebral hemispheres, suggesting that impaired efflux of aspartate from neuronal mitochondria prevents normal myelin formation.

Source Information

From the Center for Inherited Metabolic Diseases (R.W., M.B., K.N., A.W.) and the Department of Neuroradiology (T.K.), Karolinska University Hospital; and the Department of Molecular Medicine and Surgery, Center for Molecular Medicine (V.T., M.B., A.W.), the Department of Laboratory Medicine (F.H.S.), and the Department of Clinical Neuroscience (T.K.), Karolinska Institutet — both in Stockholm; the Department of Pharmaco-Biology, University of Bari, Bari, Italy (F.M.L., C.L.P., F.P.); and the Center of Child Neurology and Habilitation, Östersund Hospital, Östersund, Sweden (M.J.).

Address reprint requests to Dr. Wedell at the Department of Molecular Medicine and Surgery, Center for Molecular Medicine 02, Karolinska Institutet–Karolinska University Hospital, SE-171 76 Stockholm, Sweden, or at anna.wedell{at}ki.se.

Full Text of this Article

Related Letters:

AGC1 Deficiency and Cerebral Hypomyelination
Wolf N. I., van der Knaap M. S., Kucinski T., Palmieri F., Wedell A.
Extract | Full Text | PDF  
N Engl J Med 2009; 361:1997-1998, Nov 12, 2009. Correspondence

This article has been cited by other articles:

• Wolf, N. I., van der Knaap, M. S., Kucinski, T., Palmieri, F., Wedell, A. (2009). AGC1 Deficiency and Cerebral Hypomyelination. NEJM 361: 1997-1998 [Full Text]  
• (2009). All you need to read in the other general journals. BMJ 339: b3144-b3144 [Full Text]