Dicarboxylic aminoaciduria associated with mental retardation

Swarna, M.; Rao, D. N.; Reddy, P. P.

doi:10.1007/bf00291178

Cited by 24 publications

(14 citation statements)

References 2 publications

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“…The second case (206) was without symptoms but showed lower levels of glutamate in the urine. Mental retardation was also reported in a more recent case (366). The response of the plasma levels of aspartate and glutamate to oral loading suggests that a different glutamate transporter may be expressed in the intestine than in the kidney.…”

Section: Dicarboxylic Aminoaciduria (Omim 222730)mentioning

confidence: 82%

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Amino Acid Transport Across Mammalian Intestinal and Renal Epithelia

Bröer

2008

Physiological Reviews

833

671

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The transport of amino acids in kidney and intestine is critical for the supply of amino acids to all tissues and the homeostasis of plasma amino acid levels. This is illustrated by a number of inherited disorders affecting amino acid transport in epithelial cells, such as cystinuria, lysinuric protein intolerance, Hartnup disorder, iminoglycinuria, dicarboxylic aminoaciduria, and some other less well-described disturbances of amino acid transport. The identification of most epithelial amino acid transporters over the past 15 years allows the definition of these disorders at the molecular level and provides a clear picture of the functional cooperation between transporters in the apical and basolateral membranes of mammalian epithelial cells. Transport of amino acids across the apical membrane not only makes use of sodium-dependent symporters, but also uses the proton-motive force and the gradient of other amino acids to efficiently absorb amino acids from the lumen. In the basolateral membrane, antiporters cooperate with facilitators to release amino acids without depleting cells of valuable nutrients. With very few exceptions, individual amino acids are transported by more than one transporter, providing backup capacity for absorption in the case of mutational inactivation of a transport system.

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Section: Dicarboxylic Aminoaciduria (Omim 222730)mentioning

confidence: 82%

“…Dicarboxylic aminoaciduria is a rare disorder (206,366,372) with an estimated frequency of 1:29,000. Most affected individuals do not show symptoms (186); the inheritance is autosomal recessive.…”

Section: Dicarboxylic Aminoaciduria (Omim 222730)mentioning

confidence: 99%

Amino Acid Transport Across Mammalian Intestinal and Renal Epithelia

Bröer

2008

Physiological Reviews

833

671

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“…8,9 Physiology and molecular genetics An incidence of 1:35 000 births was estimated from a 25-year screening program in Quebec (Canada). 60 At first, an inborn error in SLC1A1 (EAAC1/EAAT3), an acidic (that is, glutamate and aspartate) amino-acid transporter (see Figure 1), was suggested to cause this disease.…”

Section: Dicarboxylic Aminoaciduria (Omim 222730) Clinical Findingsmentioning

confidence: 99%

“…4 Standard urinary amino-acid screening resulted in the identification of two other asymptomatic aminoacidurias, iminoglycinuria [5][6][7] and dicarboxylic aminoaciduria. 8,9 In principal, clinical consequences in specific aminoacidurias can arise from either the deficiency of particular amino acids (lack of absorption in the intestine and urinary loss) or the precipitation of certain amino acids (cystine) in the urine.…”

mentioning

confidence: 99%

Aminoacidurias: Clinical and molecular aspects

Camargo

Böckenhauer

Kleta

2008

Kidney International

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Inherited aminoacidurias are caused by defective amino-acid transport through renal (reabsorption) and in many cases also small intestinal epithelia (absorption). Recently, many of the genes causing this abnormal transport have been molecularly identified. In this review, we summarize the latest findings in the clinical and molecular aspects concerning the principal aminoacidurias, cystinuria, lysinuric protein intolerance, Hartnup disorder, iminoglycinuria, and dicarboxylic aminoaciduria. Signs, symptoms, diagnosis, treatment, causative or candidate genes, functional characterization of the encoded transporters, and animal models are discussed.

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“…DA is an autosomal recessive disorder with an estimated frequency of 1:36,000 (1), which was first described in 1974 (2). The clinical features of the disorder have not been widely explored, due to the paucity of clinical cases; however, of the 4 independent cases examined, 2 report an association with mental retardation (2,3). Solute carrier family 1, member 1 (SLC1A1), also referred to in human studies as excitatory amino acid transporter 3 (EAAT3) or in rodents as excitatory amino acid carrier 1 (EAAC1), is a high-affinity anionic amino acid transporter expressed in the kidney, a wide variety of epithelial tissues, brain, and eye.…”

Section: Introductionmentioning

confidence: 99%

Loss-of-function mutations in the glutamate transporter SLC1A1 cause human dicarboxylic aminoaciduria

Bailey¹,

Ryan²,

Thoeng³

et al. 2011

J. Clin. Invest.

134

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Solute carrier family 1, member 1 (SLC1A1; also known as EAAT3 and EAAC1) is the major epithelial transporter of glutamate and aspartate in the kidneys and intestines of rodents. Within the brain, SLC1A1 serves as the predominant neuronal glutamate transporter and buffers the synaptic release of the excitatory neurotransmitter glutamate within the interneuronal synaptic cleft. Recent studies have also revealed that polymorphisms in SLC1A1 are associated with obsessive-compulsive disorder (OCD) in early-onset patient cohorts. Here we report that SLC1A1 mutations leading to substitution of arginine to tryptophan at position 445 (R445W) and deletion of isoleucine at position 395 (I395del) cause human dicarboxylic aminoaciduria, an autosomal recessive disorder of urinary glutamate and aspartate transport that can be associated with mental retardation. These mutations of conserved residues impeded or abrogated glutamate and cysteine transport by SLC1A1 and led to near-absent surface expression in a canine kidney cell line. These findings provide evidence that SLC1A1 is the major renal transporter of glutamate and aspartate in humans and implicate SLC1A1 in the pathogenesis of some neurological disorders.

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Dicarboxylic aminoaciduria associated with mental retardation

Abstract: Five hundred mentally retarded children (of both sexes and under 15 years of age) referred to our institute were screened for aminoacid disorders. One case of dicarboxylic aminoaciduria was found in a girl.

Cited by 24 publications

References 2 publications

Amino Acid Transport Across Mammalian Intestinal and Renal Epithelia

Amino Acid Transport Across Mammalian Intestinal and Renal Epithelia

Aminoacidurias: Clinical and molecular aspects

Loss-of-function mutations in the glutamate transporter SLC1A1 cause human dicarboxylic aminoaciduria

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