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===='''Implications'''==== | ===='''Implications'''==== | ||
Arginino Succinate Deficiency | Arginino Succinate Deficiency | ||
The argininosuccinic acid synthetase (AS) gene is located on chromosome 9q34.1 spanning 63 kb and composed of 16 exons encoding a protein of 412 amino acids. The functional enzyme exists as a homotetramer. Surprisingly, there are at least 14 AS pseudogenes found on various chromosomes, including two pseudogenes on chromosome 9 but distant from the location of the active AS gene. There are at least 22 known mutations in the AS gene that result in argininosuccinate synthetase deficiency (ASD). Mutations include missense, nonsense and exon deletions. The frequency of ASD is approximately 1 per 57,000 live births. | The argininosuccinic acid synthetase (AS) gene is located on chromosome 9q34.1 spanning 63 kb and composed of 16 exons encoding a protein of 412 amino acids. The functional enzyme exists as a homotetramer. Surprisingly, there are at least 14 AS pseudogenes found on various chromosomes, including two pseudogenes on chromosome 9 but distant from the location of the active AS gene. There are at least 22 known mutations in the AS gene that result in argininosuccinate synthetase deficiency (ASD). Mutations include missense, nonsense and exon deletions. The frequency of ASD is approximately 1 per 57,000 live births. | ||
ASD is, like the other neonatal onset forms of UCDs, most severe when presenting in newborn infants. As with each of the four neonatal onset UCDs, ASD is characterized by the accumulation of ammonia and glutamine with clinical manifestations appearing in full-term infants with no prior obstetric risk factors. The classic symptoms appear between 24hrs and 48hrs after birth (but not prior to 24hrs) and include convulsions, hyperventilation, ataxia, hypothermia, lethargy, vomiting and poor feeding. If left untreated the hyperammonemia with result in coma and death. The severe effects of hyperammonemia are described in the Nitrogen Metabolism page. Even though sepsis is a rare event in a normal term infant with no prior obstetric complications, this disorder is misdiagnosed in almost half of neonatal UCD cases. Initial laboratory findings will include respiratory alkalosis which is the earliest objective indication of encephalopathy. The encephalopathy will progress to the point where mechanical ventilation is required. Another routine laboratory finding is reduced serum (blood) urea nitrogen (BUN) which may be as low as 1mg/dl (normal for newborns is 3–12mg/dl). If plasma ammonia levels are not measured the infants' death will be attributed to sepsis, intracranial hemorrhage, or some other disorder that would normally be associated with a pre-term delivery. | ASD is, like the other neonatal onset forms of UCDs, most severe when presenting in newborn infants. As with each of the four neonatal onset UCDs, ASD is characterized by the accumulation of ammonia and glutamine with clinical manifestations appearing in full-term infants with no prior obstetric risk factors. The classic symptoms appear between 24hrs and 48hrs after birth (but not prior to 24hrs) and include convulsions, hyperventilation, ataxia, hypothermia, lethargy, vomiting and poor feeding. If left untreated the hyperammonemia with result in coma and death. The severe effects of hyperammonemia are described in the Nitrogen Metabolism page. Even though sepsis is a rare event in a normal term infant with no prior obstetric complications, this disorder is misdiagnosed in almost half of neonatal UCD cases. Initial laboratory findings will include respiratory alkalosis which is the earliest objective indication of encephalopathy. The encephalopathy will progress to the point where mechanical ventilation is required. Another routine laboratory finding is reduced serum (blood) urea nitrogen (BUN) which may be as low as 1mg/dl (normal for newborns is 3–12mg/dl). If plasma ammonia levels are not measured the infants' death will be attributed to sepsis, intracranial hemorrhage, or some other disorder that would normally be associated with a pre-term delivery. | ||
