Editing Phenylketonuria (section)

==Signs and symptoms==
[[File:NIH microcephaly.jpg|thumb|Abnormally small head (microcephaly)]]
Untreated PKU can lead to [[intellectual disability]], [[seizure]]s, behavioral problems, and [[mental disorder]]s. It may also result in a musty smell and lighter skin. A baby born to a mother who has poorly treated PKU may have heart problems, a [[microcephaly|small head]], and [[low birth weight]].<ref name=NIH2016/>

Because the mother's body is able to break down phenylalanine during pregnancy, infants with PKU are normal at birth. The disease is not detectable by physical examination at that time, because no damage has yet been done. Newborn screening is performed to detect the disease and initiate treatment before any damage is done. The blood sample is usually taken by a [[neonatal heel prick|heel prick]], typically performed 2–7 days after birth. This test can reveal elevated phenylalanine levels after one or two days of normal infant feeding.<ref>{{Cite web |title=Phenylketonuria (PKU) Test |url=https://www.healthlinkbc.ca/medical-tests/hw41965 |url-status=dead |archive-url=https://web.archive.org/web/20180517005840/https://www.healthlinkbc.ca/medical-tests/hw41965 |archive-date=May 17, 2018 |access-date=Aug 28, 2020 |website=HealthLink BC}}</ref><ref>{{Cite journal |vauthors=Berry SA, Brown C, Grant M, Greene CL, Jurecki E, Koch J, Moseley K, Suter R, van Calcar SC, Wiles J, Cederbaum S |date=August 2013 |title=Newborn screening 50 years later: access issues faced by adults with PKU |journal=Genetics in Medicine |volume=15 |issue=8 |pages=591–9 |doi=10.1038/gim.2013.10 |pmc=3938172 |pmid=23470838}}</ref>

If a child is not diagnosed during the routine newborn screening test and a phenylalanine-restricted diet is not introduced, then phenylalanine levels in the blood will increase over time. Toxic levels of phenylalanine, along with insufficient levels of [[tyrosine]], can interfere with infant development in ways that have permanent effects. The disease may present clinically with seizures, [[hypopigmentation]] (excessively fair hair and skin), and a "musty odor" to the baby's sweat and urine (due to [[phenylacetic acid|phenylacetate]], a carboxylic acid produced by the oxidation of phenylacetone). In most cases, a repeat test should be done around two weeks of age to verify the initial test and uncover any phenylketonuria that was initially missed.<ref>{{Cite web |date=14 October 2016 |title=Phenylketonuria (PKU) |url=https://madriella.org/encyclopedia/phenylketonuria-pku/ |access-date=11 April 2021 |website=Madriella Doula Network |publisher=Madriella Network}}</ref>

Untreated children often fail to attain early developmental milestones, develop microcephaly, and demonstrate progressive impairment of cerebral function. [[Psychomotor agitation|Hyperactivity]], [[Electroencephalography|EEG]] abnormalities, seizures, and severe [[learning disability|learning disabilities]] are major clinical problems later in life. A characteristic "musty or mousy" odor on the skin, as well as a predisposition for [[eczema]], persists throughout life in the absence of treatment.<ref>{{Cite web |title=Phenylketonuria |url=https://markerdb.ca/conditions/267 |access-date=11 April 2021 |website=MarkerDB |publisher=[[David S. Wishart|Wishart Research Group]]}}</ref>

The damage done to the brain if PKU is untreated during the first months of life is not reversible. Affected children who are detected at birth and treated are much less likely to develop neurological problems or have seizures and intellectual disability, though such clinical disorders are still possible including asthma, eczema, anemia, weight gain, renal insufficiency, osteoporosis, gastritis, esophagus, and kidney deficiencies, kidney stones, and hypertension. Additionally, [[Mood disorder|mood disorders]] occur 230% higher than controls; dizziness and giddiness occur 180% higher; [[Chronic ischaemic heart disease|chronic ischemic heart disease]], [[asthma]], [[diabetes]], and [[gastroenteritis]] occur 170% higher; and [[Psychological stress|stress]] and [[adjustment disorder]] occur 160% higher.<ref name="pmid30266197">{{Cite journal |last=Burton BK, Jones KB, Cederbaum S, Rohr F, Waisbren S, Irwin DE |display-authors=etal |year=2018 |title=Prevalence of comorbid conditions among adult patients diagnosed with phenylketonuria. |journal=Mol Genet Metab |volume=125 |issue=3 |pages=228–234 |doi=10.1016/j.ymgme.2018.09.006 |pmid=30266197 |doi-access=free}}</ref><ref name="pmid31331350">{{Cite journal |last=Trefz KF, Muntau AC, Kohlscheen KM, Altevers J, Jacob C, Braun S |display-authors=etal |year=2019 |title=Clinical burden of illness in patients with phenylketonuria (PKU) and associated comorbidities - a retrospective study of German health insurance claims data. |journal=Orphanet J Rare Dis |volume=14 |issue=1 |pages=181 |doi=10.1186/s13023-019-1153-y |pmc=6647060 |pmid=31331350 |doi-access=free}}</ref> In general, however, outcomes for people treated for PKU are good. Treated people may have no detectable physical, neurological, or developmental problems at all.{{Citation needed|date=September 2024}}