Arginase Deficiency Health Article

Definition

Arginase deficiency is an inborn error of metabolism that results from a defect in the urea cycle. This cycle is a series of biochemical reactions that occur in the body in order to remove ammonia from the bloodstream.

Description

During normal cellular function, proteins are broken down into nitrogen waste products and put into the blood stream as ammonia. The urea cycle transforms this toxin into urea, which can be safely removed by the kidneys as urine. Lack of an enzyme from the urea cycle, such as arginase, can result in the buildup of toxins in the body. There are six diseases that belong in the group of urea cycle disorders. Arginase is thought to be the rarest of these disorders.

The enzyme arginase is the last step of the urea cycle, where it turns arginine into ornithine and urea. If a person is born with arginase deficiency then they build up arginine in their blood. This is called argininemia. Since earlier steps in the urea cycle are left intact, patients may or may not build up ammonia in the blood. Commonly, the build up of arginine presents as a central nervous system disease or developmental delay in young children.

Genetic profile

Arginase deficiency is an autosomal recessive trait. Thus, both parents of an affected child would have to be carriers of the gene. There are two genetically distinct arginases in the human body. The arginase that is expressed in the liver and in red blood cells is the one that is lost in arginase deficiency. This gene has been mapped to the long arm of chromosome 6, specifically 6q23. Twenty different mutations have been found in patients with the disease.

Demographics

Like other autosomal recessive diseases, arginase deficiency remains rare. The first signs of this disease tend to occur while the patient is still very young. A child may have a normal birth, infancy, and may not show any signs of the disease for quite a few years. There is no gender or racial difference (men and women are both as likely to have the disease), but its absolute incidence rate cannot be known, due its rarity and the lack of statistics. Its incidence is well below one per 200,000.

Signs and symptoms

The onset of this disease tends to be subtle. While the first symptoms of this disease show up while the patient is still a baby, some infants are said to be normal before beginning to have the symptoms. In many cases, the disease is not found at first, and the child is labeled as having "cerebral palsy" (a general term for neurologic problems that result in altered development—often starting at birth). The symptoms include: loss of normal developmental milestones (the child does not perform tasks at the usual age—walking and speaking, for example); poor feeding; not being able to eat proteins (i.e. a high protein meal makes symptoms worse); fussy behavior; lessened alertness; choreoathetotic movements (strange, uncontrollable writhing movements of limbs); spasticity of lower limbs (weakness and stiffness of legs); poor coordination; tremors; seizures; and mental retardation. Affected children may also have an enlarged liver from the buildup of toxins.

Diagnosis

Diagnosis is made after children present with symptoms. The illness should be thought for children who have both a developmental delay and stiffness of the ankles and legs that interfere with walking. It should also be thought of anytime that other urea cycle disorders are considered. The lab test of choice is to measure arginase activity in red blood cells. If patients are truly deficient then they will have below normal activity levels. In patients in which there is a high chance of disease and only mildly elevated levels of arginine in the blood, more testing should be done. In other urea cycle disorders, patients tend to have hyperammonemia (a high amount of ammonia in the blood), but in arginase deficiency the ammonia levels are rarely raised. No prenatal diagnosis is currently done. If patients have one child with this disease, then they can be counseled about risk of disease in future children. Since this disease is inherited in an autosomal recessive pattern, each time carrier parents have a child there is a 25% chance that they will have an affected child.