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Blue Diaper Syndrome

The information in NORD’s Rare Disease Database is for educational purposes only. It should never be used for diagnostic or treatment purposes. If you have questions regarding a medical condition, always seek the advice of your physician or other qualified health professional. NORD’s reports provide a brief overview of rare diseases. For more specific information, we encourage you to contact your personal physician or the agencies listed as “Resources” on this report.

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NORD is very grateful to Uri S. Alon, MD, Professor of Pediatrics, Director, Bone and Mineral Disorders Clinic, Section of Pediatric Nephrology, The Children's Mercy Hospital and Clinics, University of Missouri at Kansas City School of Medicine, for assistance in the preparation of this report.

Synonyms of Blue Diaper Syndrome

Disorder Subdivisions

General Discussion

Blue diaper syndrome is a rare, genetic metabolic disorder characterized by the incomplete intestinal breakdown of tryptophan, a dietary nutrient. Symptoms typically include digestive disturbances, fever, irritability and visual difficulties. Some children with blue diaper syndrome may also develop kidney disease. Infants with this disorder may have bluish urine-stained diapers. Blue diaper syndrome is inherited as an autosomal or X-linked recessive trait.

Symptoms

Blue diaper syndrome is a rare inborn error metabolism that is usually detected when urine produces unusual blue stains on an infant's diapers (indoluria). This occurs when intestinal bacteria break down excessive amounts of unabsorbed tryptophan.

Symptoms of blue diaper syndrome may include irritability, constipation, poor appetite, vomiting, and the failure to grow and gain weight at the expected rate (failure to thrive). Some children with Blue diaper syndrome may have frequent fevers and intestinal infections.

Additional symptoms may include poor vision and abnormally high levels of calcium in the blood (hypercalcemia). Excessive calcium may accumulate in the kidneys (nephrocalcinosis) leading to impaired kidney function and possible kidney failure.

Some infants may have eye abnormalities including underdevelopment (hypoplasia) of the optic disc, abnormal eye movements, and an abnormally small cornea (microcornea), the front, clear portion of the eye through which light passes.

Causes

Blue diaper syndrome is a rare disorder inherited as an autosomal recessive trait although X-linked recessive inheritance has not been completely ruled out. Genetic diseases are determined by two genes, one received from the father and one from the mother.

Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%.

X-linked recessive genetic disorders are conditions caused by an abnormal gene on the X chromosome. Females have two X chromosomes but one of the X chromosomes is "turned off" and all of the genes on that chromosome are inactivated. Females who have a disease gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms of the disorder because it is usually the X chromosome with the abnormal gene that is "turned off". Males have one X chromosome and if they inherit an X chromosome that contains a disease gene, they will develop the disease. Males with X-linked disorders pass the disease gene to all of their daughters, who will be carriers. Males can not pass an X-linked gene to their sons because males always pass their Y chromosome instead of their X chromosome to male offspring. Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% to have a son affected with the disease, and a 25% chance to have an unaffected son.

Symptoms, such as the blue urine stains on diapers, develop due to the intestinal breakdown of excessive amounts of tryptophan and the accumulation of indican and related compounds (e.g., indigotin) in the urine (indicanuria). When tryptophan is broken down by intestinal bacteria, it is converted into an organic compound called indole. Indole is absorbed and broken down into another organic compound called indican. When exposed to air, indican converts into indigo blue dye giving the urine a distinctive blue color. Although the exact nature of the biochemical defect remains uncertain, it is believed to be related to a defect in the intestinal absorption and transport of tryptophan.

Affected Populations

Blue diaper syndrome is an extremely rare metabolic disorder that affects males and females in equal numbers. The incidence of the disorder in the general population is unknown.

Related Disorders

Symptoms of the following disorder can be similar to those of blue diaper syndrome. Comparison may be useful for a differential diagnosis.

Intestinal infections with the bacteria Pseudomonas aeruginosa can produce a blue discoloration of the stools. This can lead to a bluish appearance on a diaper and may be confused initially with blue diaper syndrome. Symptoms may include diarrhea, poor feeding habits, and irritability.

Standard Therapies

Diagnosis
A diagnosis of blue diaper syndrome is made based upon a thorough clinical evaluation, a detailed patient history, identification of characteristic symptoms, and the demonstration of indican in a fresh urine sample (indicanuria).

Treatment
Children with blue diaper syndrome may be put on a diet that restricts their intake of calcium. It is hoped that a calcium restricted diet may help to prevent kidney damage. The diet should also be low in protein and the amount of vitamin D should be limited. Antibiotics may be administered to reduce or eliminate certain intestinal bacteria. Nicotinic acid may also be beneficial to control intestinal infections. Foods with high levels of tryptophan should be avoided, such as turkey and warm milk.

Genetic counseling will of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

Blue Diaper Syndrome Resources

NORD Member Organizations:

(To become a member of NORD, an organization must meet established criteria and be approved by the NORD Board of Directors. If you're interested in becoming a member, please contact Susan Olivo, Membership Manager, at solivo@rarediseases.org.)

Other Organizations:

References

TEXTBOOKS
Alon US. Blue Diaper Syndrome. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:681.

Yamada T, Alpers DH, Kaplowitz N, Laine L, et al., eds. Textbook for Gastroenterology. 4th ed. Lippincott Williams & Wilkins. Philadelphia, PA; 2003:2635.

Brenner BM, Rector Jr FC. The Kidney. 4th ed. W.B. Saunders Company. Philadelphia, PA; 1991:1601.

Buyce ML. Editor-in-Chief. Birth Defects Encyclopedia. Blackwell Scientific Publications. Center for Birth Defects Information Services, Inc., Dover, MA; 1990:1712.

JOURNAL ARTICLES
Chen Y, Wu L, Xiong Q. The ocular abnormalities of blue diaper syndrome. Metab Pediatr Syst Ophthalmol. 1991;14:73-5.

Libit SA, Ulstrom RA, Doeden D. Fecal Pseudomonas aeruginosa as a cause of the blue diaper syndrome. J Pediatr. 1972;81:546-7.

Drummond KN, Michael AF, Ulstrom RA, Good RA. The blue diaper syndrome: familial hypercalcemia with nephrocalcinosis and indicanuria; a new familial disease, with definition of the metabolic abnormality. Am J Med. 1964;37:928-48.

FROM THE INTERNET
McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:211000; Last Update:06/10/1997. Available at: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=211000 Accessed On: August, 2006.

Report last updated: 2009/04/27 00:00:00 GMT+0