© 2017, GENASSIST, Inc.     

By Keith S. Wexler, MBA, Maternal Fetal Medicine, Prenatal Diagnosis and Biotech/Life Sciences Consultant, GENASSIST, Inc.

Paul Wexler, M.D., F.A.C.O.G., Medical Director, GENASSIST, Inc.

Clinical Professor, Department of OB/GYN, University of Colorado Health Sciences Center

Clinical Professor, Division of Genetics/Dept. of Pediatrics, Univ. of Colorado/The Children’s Hospital


[*A recent study, that is ongoing, has suggested a possible relationship between maternal age (35 years or older) and/or paternal age (greater than 40 years) and autism and/or autism spectrum disorder(s) in a child. Reference: Israel & Mt. Sinai, NY.

*Some recent studies have suggested risk may be as high as 1:50 to 1:80.]



Ornithine Transcarbamylase Deficiency (OTC):

Ornithine Transcarbamylase Deficiency (OTC) is the most common enzyme deficiency in the urea cycle.

Ornithine Transcarbamylase Deficiency (OTC) is carried on the X chromosome at Xp11.4. Over 200 mutations in the gene have been described which probably accounts for the variability in the presentation of the disorder.

Additionally, at least 5 other enzyme deficiencies which have a role in the urea cycle have been described:

Ammonia (NH3) which is produced by the breakdown of proteins in the body by intestinal bacteria (broken down by liver mitochondria) into urea which is excreted in the urine.

Ornithine Transcarbamylase Deficiency (OTC) leads to increased ammonia levels in the blood.

Severe disease may appear by Day 2 or Day 3 of life and may be life threatening.

Males inheriting the deleterious X chromosome are typically more seriously affected than heterozygous females. However, up to 20% of females may manifest symptoms and hyperammonemia can represent a crisis even in females.  Complications may include:

  • Attention deficit
  • Learning Problems
  • Hyperactivity
  • Seizures and/or coma

Some individuals with milder disease may not manifest symptoms until later childhood or adulthood. Milder disease symptoms may include:

  • Headache
  • Mental confusion
  • Movement disorders
  • Visual disturbances

The prevalence of Ornithine Transcarbamylase Deficiency (OTC) is approximately 1 in 50,000 to 1 in 80,000 births.

Urea Cycle disorders involving any of the Urea Cycle enzymes are slightly more frequent at approximately 1 in 35,000 births. Symptoms may be similar for any of the urea cycle enzyme deficiencies.

Deficiency of one or more enzymes in Amino Acid Metabolism can result in multiple diseases usually inherited in an autosomal recessive manner (25% if both parents are gene carriers) and less commonly in an X-linked manner. Buildup of various acids in the blood, called Organic Acidemia, and/or Organic Aciduria can cause similar symptoms to those seen in Urea Cycle Disturbances.

The prevalence of Organic Acidemias is approximately 1 in 50,000 to 1 in 100,000 births

Diagnosis of Ornithine Transcarbamylase Deficiency (OTC) and differentiated from Organic Acidemias may be made by detection of abnormal levels of amino acids with high acylcarnitine, high glutamine, high orotic acid and low citruline in the plasma and/or urine of patients. Occasionally, the diagnosis is made by tissue biopsy.

DNA testing may diagnose up to 80% of patients with Ornithine Transcarbamylase Deficiency (OTC).

Treatment of Ornithine Transcarbamylase Deficiency (OTC) is aimed at prevention of hyperammonemia and some dietary restrictions to limit some protein intake and supplement of essential amnio acids.

Occasionally, a feeding tube or gastrostomy is required and sodium phylbutycate, sodium phenylacetate or sodium benzoate may be prescribed.

Hemodialysis and/or liver transplantation may become necessary in the most severe cases.