Citrin is the aspartate-glutamate carrier protein (AGC: aspartate-glutamate carrier) in the mitochondrial membrane that are important in the synthesis of urea, proteins, nucleotides and gluconeogenesis (Ngu et al., 2010). Citrin presence will allow the exchange of aspartate in the mitochondria with glutamate in the cytosol and a proton. This function is important in the transfer of nicotinamide adenine dinucleotide (NADH) to balance the mitochondria as part of the malate-aspartate shuttle. NADH generated by malate oxidized generate adenosine triphosphate (ATP) on the oxidative phosphorylation pathway. AGC-specific protein plays an important supplier of aspartate to argininosuccinate synthetase (ASS) in the cytosol and produce argininosuccinate in the urea cycle.
Thus, the lack of specific AGC in the liver (Citrin) will make the urea cycle dysfunction and hyperammonemia occurs. (Komatsu et al., 2008, Fernandes, 2006, Rodwell, 2006)Citrin deficiency is an autosomal recessive genetic disease caused by mutations of the gene SLC25A13 (Vajro and Veropalumbo, 2010, Ngu et al., 2010, Fu et al., 2010). These disorders can be characterized by progressive liver disease that usually begins in adolescence with the end result of cirrhosis.
Citrulinemia differentiated into two phenotypes, namely:
a. Citrulinemia type I
Type I Citrulinemia also known as classical citrulinemia, usually appear several days after birth. In type I occurs due to mutations in genes encoding aspartate aminosuksinat synthetase, an enzyme that serves to change citrulin arginosuksinat with aspartic acid in the cytosol. Citrulin will accumulate outside the mitochondria so that the urea cycle is not running. Affected babies appear normal at birth but blood ammonia levels that will provide increased energy deficiency symptoms (lethargy), poor feeding, vomiting, seizures, and loss of consciousness. The situation is in some cases very severe and life-threatening. Mild type I citrulinemia types can develop into adults in later life. Some people with gene mutations that cause citrulinemia type I also can not show abnormalities due to the formation of the enzyme aspartate compensation aminosuksinat synthetase II (Thoene, 1993).
b. Citrulinemia type II
Citrulinemia type II is generally attacks the nervous system, disorders of consciousness, weakness, impaired meori, deviant behavior (agitation and hyperactivity), seizures. Citrulinemia type II occurs due to the gene encoding gengguan Citrin, aspartate glutamate carrier. Disturbances in these carriers causes a lot of aspartate in the mitochondria can not easily escape to the cytosol in exchange for glutamate sehinggan citulin can not be converted into aspartic acid enzyme arginosuksinat arginosuksinat although I normally synthetase. As a consequence is the buildup citrulin and the cessation of the urea cycle.
In some cases, signs and symptoms seen in adults (adult onset) that can be life-threatening and can be triggered by several triggers such as infection, drugs, alcohol and called CTNL2 surgery. Abnormalities in children known as the Neonatal intrahepatic cholestasis Caused by Citrin Deficiency (NICCD) (Fu et al., 2010, Ohura et al., 2007, Tamamori et al., 2004, Takagi et al., 2006).
During infancy, some individuals with SLC25A13 gene revealed homozygous mutations with cholestatic liver disease intrahepatal, although the symptoms are temporary and self limiting in most cases. Activity of arginine succinate synthetase (ASS) in the liver is affected, but activity in other parts of the body is not affected even no mutation in the gene ASS. Definitive diagnosis is made possible by genetic analysis for several mutations. These disorders have a higher incidence in the population of East Asia as one of the commonest causes of hyperammonemia in adults. (Endo et al., 2004)
Provision of arginine effective in treating hyperammonemia, however, the effects are temporary. Specific treatment has not been determined, and liver transplantation is needed for cases with liver failure. (Endo et al., 2004)Citrin deficiency especially NICCD should be aware in all children with prolonged intrahepatic cholestasis. Of the 47 children with neonatal cholestasis in the study of Ko et al in Korea, found 11 children with biliary atresia, 4 children with congenital TORCH infections, 2 children with the syndrome Allagile and 21 children is not known why. NICCD was diagnosed in 3 children (6%) (Ko et al., 2007).
Initial evaluation of children with cholestasis including ultrasoundgrafi, duodenal aspiration and biopsy can mengeklusi percutaneous biliary atresia. Liver biopsy is also necessary to detect the presence of Allagile syndrome, Dubin Johnson syndrome and progressive familial intrahepatic cholestasis (PFIC). GGT levels of fun also helps because the low levels often found in cholestasis PFIC.
Amino acid analysis is useful in screening metabolic abnormalities such as NICCD (Ko et al., 2007, Ngu et al., 2010).Differential diagnoses include CTLN2 argininosuksinic pyruvate carboxylase deficiency asiduria and which showed an increase in plasma and urine sitrulin. Hiperamonia strengthen urea.selain alleged defect in the cycle, the neonates with cholestasis have investigated the possibility of occurrence of galactosemia and other hyperbilirubinemia (Thong et al., 2010).
REFERENCES
Thus, the lack of specific AGC in the liver (Citrin) will make the urea cycle dysfunction and hyperammonemia occurs. (Komatsu et al., 2008, Fernandes, 2006, Rodwell, 2006)Citrin deficiency is an autosomal recessive genetic disease caused by mutations of the gene SLC25A13 (Vajro and Veropalumbo, 2010, Ngu et al., 2010, Fu et al., 2010). These disorders can be characterized by progressive liver disease that usually begins in adolescence with the end result of cirrhosis.
Citrulinemia differentiated into two phenotypes, namely:
a. Citrulinemia type I
Type I Citrulinemia also known as classical citrulinemia, usually appear several days after birth. In type I occurs due to mutations in genes encoding aspartate aminosuksinat synthetase, an enzyme that serves to change citrulin arginosuksinat with aspartic acid in the cytosol. Citrulin will accumulate outside the mitochondria so that the urea cycle is not running. Affected babies appear normal at birth but blood ammonia levels that will provide increased energy deficiency symptoms (lethargy), poor feeding, vomiting, seizures, and loss of consciousness. The situation is in some cases very severe and life-threatening. Mild type I citrulinemia types can develop into adults in later life. Some people with gene mutations that cause citrulinemia type I also can not show abnormalities due to the formation of the enzyme aspartate compensation aminosuksinat synthetase II (Thoene, 1993).
b. Citrulinemia type II
Citrulinemia type II is generally attacks the nervous system, disorders of consciousness, weakness, impaired meori, deviant behavior (agitation and hyperactivity), seizures. Citrulinemia type II occurs due to the gene encoding gengguan Citrin, aspartate glutamate carrier. Disturbances in these carriers causes a lot of aspartate in the mitochondria can not easily escape to the cytosol in exchange for glutamate sehinggan citulin can not be converted into aspartic acid enzyme arginosuksinat arginosuksinat although I normally synthetase. As a consequence is the buildup citrulin and the cessation of the urea cycle.
In some cases, signs and symptoms seen in adults (adult onset) that can be life-threatening and can be triggered by several triggers such as infection, drugs, alcohol and called CTNL2 surgery. Abnormalities in children known as the Neonatal intrahepatic cholestasis Caused by Citrin Deficiency (NICCD) (Fu et al., 2010, Ohura et al., 2007, Tamamori et al., 2004, Takagi et al., 2006).
During infancy, some individuals with SLC25A13 gene revealed homozygous mutations with cholestatic liver disease intrahepatal, although the symptoms are temporary and self limiting in most cases. Activity of arginine succinate synthetase (ASS) in the liver is affected, but activity in other parts of the body is not affected even no mutation in the gene ASS. Definitive diagnosis is made possible by genetic analysis for several mutations. These disorders have a higher incidence in the population of East Asia as one of the commonest causes of hyperammonemia in adults. (Endo et al., 2004)
Provision of arginine effective in treating hyperammonemia, however, the effects are temporary. Specific treatment has not been determined, and liver transplantation is needed for cases with liver failure. (Endo et al., 2004)Citrin deficiency especially NICCD should be aware in all children with prolonged intrahepatic cholestasis. Of the 47 children with neonatal cholestasis in the study of Ko et al in Korea, found 11 children with biliary atresia, 4 children with congenital TORCH infections, 2 children with the syndrome Allagile and 21 children is not known why. NICCD was diagnosed in 3 children (6%) (Ko et al., 2007).
Initial evaluation of children with cholestasis including ultrasoundgrafi, duodenal aspiration and biopsy can mengeklusi percutaneous biliary atresia. Liver biopsy is also necessary to detect the presence of Allagile syndrome, Dubin Johnson syndrome and progressive familial intrahepatic cholestasis (PFIC). GGT levels of fun also helps because the low levels often found in cholestasis PFIC.
Amino acid analysis is useful in screening metabolic abnormalities such as NICCD (Ko et al., 2007, Ngu et al., 2010).Differential diagnoses include CTLN2 argininosuksinic pyruvate carboxylase deficiency asiduria and which showed an increase in plasma and urine sitrulin. Hiperamonia strengthen urea.selain alleged defect in the cycle, the neonates with cholestasis have investigated the possibility of occurrence of galactosemia and other hyperbilirubinemia (Thong et al., 2010).
REFERENCES
Tidak ada komentar:
Posting Komentar