Can untreated PKU patients escape from intellectual disability?

TY - JOUR

T1 - Can untreated PKU patients escape from intellectual disability?

T2 - A systematic review

AU - van Vliet, Danique

AU - van Wegberg, Annemiek M J

AU - Ahring, Kirsten

AU - Bik-Multanowski, Miroslaw

AU - Blau, Nenad

AU - Bulut, Fatma D

AU - Casas, Kari

AU - Didycz, Bozena

AU - Djordjevic, Maja

AU - Federico, Antonio

AU - Feillet, François

AU - Gizewska, Maria

AU - Gramer, Gwendolyn

AU - Hertecant, Jozef L

AU - Hollak, Carla E M

AU - Jørgensen, Jens V

AU - Karall, Daniela

AU - Landau, Yuval

AU - Leuzzi, Vincenzo

AU - Mathisen, Per

AU - Moseley, Kathryn

AU - Mungan, Neslihan Ö

AU - Nardecchia, Francesca

AU - Õunap, Katrin

AU - Powell, Kimberly K

AU - Ramachandran, Radha

AU - Rutsch, Frank

AU - Setoodeh, Aria

AU - Stojiljkovic, Maja

AU - Trefz, Fritz K

AU - Usurelu, Natalia

AU - Wilson, Callum

AU - van Karnebeek, Clara D

AU - Hanley, William B

AU - van Spronsen, Francjan J

PY - 2018/8/29

Y1 - 2018/8/29

N2 - BACKGROUND: Phenylketonuria (PKU) is often considered as the classical example of a genetic disorder in which severe symptoms can nowadays successfully be prevented by early diagnosis and treatment. In contrast, untreated or late-treated PKU is known to result in severe intellectual disability, seizures, and behavioral disturbances. Rarely, however, untreated or late-diagnosed PKU patients with high plasma phenylalanine concentrations have been reported to escape from intellectual disability. The present study aimed to review published cases of such PKU patients.METHODS: To this purpose, we conducted a literature search in PubMed and EMBASE up to 8th of September 2017 to identify cases with 1) PKU diagnosis and start of treatment after 7 years of age; 2) untreated plasma phenylalanine concentrations ≥1200 μmol/l; and 3) IQ ≥80. Literature search, checking reference lists, selection of articles, and extraction of data were performed by two independent researchers.RESULTS: In total, we identified 59 published cases of patients with late-diagnosed PKU and unexpected favorable outcome who met the inclusion criteria. Although all investigated patients had intellectual functioning within the normal range, at least 19 showed other neurological, psychological, and/or behavioral symptoms.CONCLUSIONS: Based on the present findings, the classical symptomatology of untreated or late-treated PKU may need to be rewritten, not only in the sense that intellectual dysfunction is not obligatory, but also in the sense that intellectual functioning does not (re)present the full picture of brain damage due to high plasma phenylalanine concentrations. Further identification of such patients and additional analyses are necessary to better understand these differences between PKU patients.

AB - BACKGROUND: Phenylketonuria (PKU) is often considered as the classical example of a genetic disorder in which severe symptoms can nowadays successfully be prevented by early diagnosis and treatment. In contrast, untreated or late-treated PKU is known to result in severe intellectual disability, seizures, and behavioral disturbances. Rarely, however, untreated or late-diagnosed PKU patients with high plasma phenylalanine concentrations have been reported to escape from intellectual disability. The present study aimed to review published cases of such PKU patients.METHODS: To this purpose, we conducted a literature search in PubMed and EMBASE up to 8th of September 2017 to identify cases with 1) PKU diagnosis and start of treatment after 7 years of age; 2) untreated plasma phenylalanine concentrations ≥1200 μmol/l; and 3) IQ ≥80. Literature search, checking reference lists, selection of articles, and extraction of data were performed by two independent researchers.RESULTS: In total, we identified 59 published cases of patients with late-diagnosed PKU and unexpected favorable outcome who met the inclusion criteria. Although all investigated patients had intellectual functioning within the normal range, at least 19 showed other neurological, psychological, and/or behavioral symptoms.CONCLUSIONS: Based on the present findings, the classical symptomatology of untreated or late-treated PKU may need to be rewritten, not only in the sense that intellectual dysfunction is not obligatory, but also in the sense that intellectual functioning does not (re)present the full picture of brain damage due to high plasma phenylalanine concentrations. Further identification of such patients and additional analyses are necessary to better understand these differences between PKU patients.

KW - Female

KW - Humans

KW - Intellectual Disability/blood

KW - Male

KW - Phenylalanine/blood

KW - Phenylketonurias/blood

U2 - 10.1186/s13023-018-0890-7

DO - 10.1186/s13023-018-0890-7

M3 - SCORING: Journal article

C2 - 30157945

VL - 13

SP - 149

JO - ORPHANET J RARE DIS

JF - ORPHANET J RARE DIS

SN - 1750-1172

IS - 1

ER -