NORD gratefully acknowledges 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.
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.
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.
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.
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.
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).
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.
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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.