Why does phenylketonuria cause mental retardation

There currently is no cure for PKU, but the condition is controllable through proper diet and supplements. This is consistent with the recent findings of the systematic review by Medford including 29 articles representing PKU patients of all ages, who found that the main factor associated with worsening of metabolic control was age [9], as well as a less recent retrospective chart review related to PKU ….

If PKU is confirmed, treatment will be given straight away to reduce the risk of serious complications. Treatment includes a special diet and regular blood tests. With early diagnosis and the correct treatment, most children with PKU are able to live healthy lives.

Ask the healthcare provider what the test results mean for your child. The test screens for blood levels of phenylalanine. As PKU is inherited in an autosomal recessive fashion, all children of a mother with PKU will inherit 1 affected gene.

PKU is passed down through families. For a baby to have the disease, he or she must get inherit the PKU gene from both parents. Pregnancy and Phenylketonuria PKU Girls or women with PKU can have healthy children as long as they are aware of and maintain strict adherence to their low phenylalanine diet throughout their pregnancy. Children with PKU have lower levels of melanin, the substance that gives color to hair and skin. As a result, children with PKU often will have pale skin, blond hair and blue eyes.

The incidence of carriers in the general population is approximately one in fifty people, but the chance that two carriers will mate is only one in [2].

Begin typing your search term above and press enter to search. Press ESC to cancel. Ben Davis March 27, Why does PKU cause mental retardation? This pattern of inheritance is called autosomal recessive. It's possible for a parent to be a carrier — to have the defective gene that causes PKU, but not have the disease. If only one parent has the defective gene, there's no risk of passing PKU to a child, but it's possible for the child to be a carrier.

Most often, PKU is passed to children by two parents who are carriers of the disorder, but don't know it. Untreated PKU can lead to complications in infants, children and adults with the disorder. When mothers with PKU have high blood phenylalanine levels during pregnancy, fetal birth defects or miscarriage can occur. Mayo Clinic does not endorse companies or products. Advertising revenue supports our not-for-profit mission.

This content does not have an English version. This content does not have an Arabic version. Overview Phenylketonuria fen-ul-key-toe-NU-ree-uh , also called PKU, is a rare inherited disorder that causes an amino acid called phenylalanine to build up in the body. Email address.

First Name let us know your preferred name. Last Name. Thank you for subscribing Your in-depth digestive health guide will be in your inbox shortly. Sorry something went wrong with your subscription Please, try again in a couple of minutes Retry. Request an Appointment at Mayo Clinic. Autosomal recessive inheritance pattern Open pop-up dialog box Close. Autosomal recessive inheritance pattern To have an autosomal recessive disorder, you inherit two mutated genes, one from each parent.

Share on: Facebook Twitter. Show references National Library of Medicine. Genetics Home Reference. Accessed Oct. The low protein substitutes and synthetic formula supplements for natural protein products may be nonpalatable.

Expense may be an issue. Dietary restrictions may limit social interactions. Ongoing physician visits and laboratory testing requiring blood sampling may be burdensome and expensive. All of these problems are certainly surmountable but do contribute a certain amount of difficulty for patients and their families. Sapropterin dihydrochloride 6R-BH4 pharmacologic cofactor therapy does offer chances for liberalization of dietary restrictions, alleviating some of the above problems.

There have been no serious side effects thus far reported. Gastrointestinal complications include gastric distress, nausea, and diarrhea. These are usually mild and self limited and may be avoided in many by taking the medicine with food. The full effects of this therapy on pregnancy remain to be observed but its use in several pregnancies has been tolerated without complication.

Patients with classic PKU demonstrate mental retardation often IQs of 50 or less if untreated in the vast majority of cases. Some studies suggest a loss of up to 50 IQ points during the first infant year on unrestricted diet. In contrast, patients placed on dietary restriction of phenylalanine within the first few weeks of life have outcomes that fall within the normal range. There are slight differences between PKU patients and their age-matched non-PKU siblings in measures of intelligence and behavior.

These include increased frequency of ADHD, decreased autonomy, and increased school problems compared to either healthy controls or chronically ill peers. It is currently not known whether lifetime outcomes will change if sapropterin dihydrochloride 6R-BH4 therapy is used concurrently with restricted diet.

Restricted diet is recommended lifelong, although once past 12 years of age, some liberalization appears to be well tolerated. Prematurely normalizing the diet has been associated with loss of a few but variable IQ points, abnormal mannerisms, hyperactivity, signs of anxiety, and variable other behavioral and school performance issues. The problems of restarting the restricted diet to prevent maternal PKU syndrome has been addressed in the above sections.

Specialists in the United States and many other sites prefer to see levels remain less than micromoles per liter during the first childhood years, with liberalization thereafter. This usually will be achieved only through prompt acceptance of full dietary restriction.

This is another reason for the practice of lifelong dietary restriction. Despite lifelong treatment with restricted diet, there still is an increased risk for psychiatric abnormalities, attention deficits, anxiety, and other social disabling conditions. Overall, however, the outcomes of early treatment are considered excellent with few risks and limited hardships compared to the benefits. PKU is considered the most common aminoaciduria and identified inborn error of metabolism associated with mental retardation.

For example, Finland has a very low incidence, ,, similar to the low incidence observed in the Ashkenazi Jewish populations in several geographic locations. In contrast, Ireland , and Turkey , have much higher incidences, suggesting a fold range in prevalence by population.

As explained above, insufficient PAH activity allows accumulation of excess phenylalanine in body tissues. This amino acid and its converted metabolites ie. Appropriate treatment prevents the mental retardation but there may be variable mild abnormalities in intelligence, behavior and neuropsychiatric attributes.

Patients on treated with dietary restriction must be closely monitored for other nutritional deficiencies. There are hundreds of mutant PAH alleles identified. Usually a first child with PKU is identified in the family such as by neonatal screening and subsequent mutation testing identifies carrier status in other family members.

Prenatal diagnosis is available through chorionic villus sampled cells or amniotic fluid cells obtained during pregnancy and allows for reproductive choices. This has been achieved through standardized neonatal screening efforts coordinated with close followup of positive results. Dietary restriction of phenylalanine intake is initiated while testing for the rare biopterin cofactor defects is pursued, since the latter will require some differences in treatment supplements.

Prevention of the development of mental retardation is tied directly to the time of initiation and continuity of dietary restriction in the vast majority of cases. Dietary recommendations require ongoing nutritional counseling from experienced professionals. Knowledge of harmful components in offered foods requires provision of constantly updated information to patients and their families. For example, the widespread use of the artificial sweetener aspartame N-aspartylphenylalanine ester represents a potential source of unaccounted for phenylalanine in an otherwise restricted diet.

This compound is hydrolyzed by the intestinal luminal digestive process to release free L-phenylalanine, which is directly absorbed into the bloodstream.

Similar components of foods and drinks may be introduced into the commercial market at any time, and the caretakers and families need to be aware in order to assure optimal dietary management and outcomes. A comprehensive review of the genetics, classification schemes, and approaches to diagnosis and treatment. An excellent but lengthy review for clinicians.

Camp, KM. Mol Genet Metab. A very comprehensive review of the current state of diagnosis and treatment, including clarifications of historical categorizations, and consensus approaches to treatments and future research. Includes BH4 pharmacologic interventions.

Pediatric Endocrinology and Inborn Errors of Metabolism An excellent clinically oriented discussion of the approaches to diagnosis and treatment, as well as approaches to screening. Hodder Arnold. An excellent clinical review of the condition, including a comprehensive protocol for diagnosis and treatment. An excellent comprehensive review of all aspects of biochemistry and genetics of the disease and its clinical complications.

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