Treatment, information and support urea cycle disorders, OTC deficiency, ASA lyase, citrullinemia, CPS1

Types of urea cycle disorders, OTC deficiency, ASA lyase, CPS1, citrullinemia, HHH

There are six enzyme disorders of the urea cycle, collectively known as inborn errors of urea synthesis, or urea cycle enzyme defects. Each is referred to by the initials of the missing enzyme.

CPS1 - Carbamyl Phosphate Synthetase    

NAGS- N-Acetylglutamate Synthetase                            

OTC Deficiency - Ornithine Transcarbamylase

AS - Argininosuccinic Acid Synthetase (Citrullinemia)

ASL - Argininosuccinate Lyase (Argininosuccinic Aciduria)

AG - Arginase

Additionally, there are three transporter defects:

Mitochondrial ornithine carrier (Hyperornithinemia-Hyperammonemia-Homocitrullinemia or HHH syndrome)
Mitochondrial aspartate/glutamate carrier (Citrullinemia Type II, also known as Citrin Deficiency)
Dibasic amino acid carrier (Hyperdibasic Amino Aciduria or Lysinuric Protein Intolerance)

Urea cycle disorders affect individuals of all ages - infants, children, teenagers and adults. There are two types of onset - neonatal onset and late onset. Over 69% of cases occur outside the newborn period (neonatal onset). Late-onset UCD refers to individuals who present with symptoms at any age outside the newborn period. The spectrum of severity in late-onset UCD is widely variable ranging from very mild to severe depending on the genetic mutation involved.

Neonatal onset disorders are caused by severe enzyme deficiencies or complete absence of enzyme function.  Individuals with childhood or adult onset disease have partial enzyme deficiencies.  The percentage, or amount of enzyme function, and therefore ability to rid the body of ammonia varies widely between individuals with partial enzyme deficiencies.  All of these disorders are transmitted genetically as autosomal recessive genes - each parent contributes a defective gene to the child - except for Ornithine Transcarbamylase Deficiency.  OTC deficiency is acquired in one of three ways: as an X-linked trait from the mother, who may be an undiagnosed carrier; in some cases of female children, the disorder can also be inherited from the defect on the father's X-chromosome; and finally, OTC deficiency may be acquired as a "new" spontaneous mutation, called a de novo mutation, occurring in the fetus. Recent research has shown that some female carriers of the disease may become symptomatic with the disorder later in life, suffering high ammonia levels and experiencing classic symptoms. Undiagnosed OTC carrier women are at risk for potentially fatal elevated ammonia levels, especially following childbirth or as a result of dieting, gastric bypass or extreme exercising.

Male child with OTC deficiency

A.G., OTC Deficiency, Argentina

When the diagnosis of citrullinemia was confirmed, we started looking for information on the Internet about UCDs or for people who were willing to help us, and that’s how we found NUCDF. We not only got all the information we needed to know about this rare disease, we received words of hope and love during those days of frustration, fear and sadness. A.R.