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Mild hyperphenylalaninemia

MedGen UID:
1843033
Concept ID:
C5680207
Disease or Syndrome
Synonyms: mHPA; Mild HPA; mild HPA; mild hyperphenylalaninemia; Non-PKU HPA; non-PKU HPA
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Monarch Initiative: MONDO:0019335
Orphanet: ORPHA79651

Definition

A rare form of phenylketonuria, an inborn error of amino acid metabolism, characterized by blood phenylalanine (Phe) concentrations of 120-600 micromol/L with or without clinical manifestations of impaired cognitive function, and behavioral and developmental disorders. [from ORDO]

Professional guidelines

PubMed

Aldámiz-Echevarría L, Llarena M, Bueno MA, Dalmau J, Vitoria I, Fernández-Marmiesse A, Andrade F, Blasco J, Alcalde C, Gil D, García MC, González-Lamuño D, Ruiz M, Ruiz MA, Peña-Quintana L, González D, Sánchez-Valverde F, Desviat LR, Pérez B, Couce ML
J Hum Genet 2016 Aug;61(8):731-44. Epub 2016 Apr 28 doi: 10.1038/jhg.2016.38. PMID: 27121329
Jeannesson-Thivisol E, Feillet F, Chéry C, Perrin P, Battaglia-Hsu SF, Herbeth B, Cano A, Barth M, Fouilhoux A, Mention K, Labarthe F, Arnoux JB, Maillot F, Lenaerts C, Dumesnil C, Wagner K, Terral D, Broué P, de Parscau L, Gay C, Kuster A, Bédu A, Besson G, Lamireau D, Odent S, Masurel A, Guéant JL, Namour F
Orphanet J Rare Dis 2015 Dec 15;10:158. doi: 10.1186/s13023-015-0375-x. PMID: 26666653Free PMC Article
Burnett JR
IDrugs 2007 Nov;10(11):805-13. PMID: 17968763

Curated

American College of Medical Genetics and Genomics, Newborn Screening ACT Sheet, Elevated Phenylalanine, Phenylalanine hydroxylase deficiency (PAH), 2022

American College of Medical Genetics and Genomics, Algorithm, PAH deficiency: Elevated Phenylalanine, 2022

Recent clinical studies

Etiology

Jeannesson-Thivisol E, Feillet F, Chéry C, Perrin P, Battaglia-Hsu SF, Herbeth B, Cano A, Barth M, Fouilhoux A, Mention K, Labarthe F, Arnoux JB, Maillot F, Lenaerts C, Dumesnil C, Wagner K, Terral D, Broué P, de Parscau L, Gay C, Kuster A, Bédu A, Besson G, Lamireau D, Odent S, Masurel A, Guéant JL, Namour F
Orphanet J Rare Dis 2015 Dec 15;10:158. doi: 10.1186/s13023-015-0375-x. PMID: 26666653Free PMC Article
Mitchell JJ, Trakadis YJ, Scriver CR
Genet Med 2011 Aug;13(8):697-707. doi: 10.1097/GIM.0b013e3182141b48. PMID: 21555948
Campistol J, Gassió R, Artuch R, Vilaseca MA; PKU Follow-up Unit
Dev Med Child Neurol 2011 May;53(5):405-8. Epub 2011 Mar 21 doi: 10.1111/j.1469-8749.2010.03869.x. PMID: 21418193
Hanley WB
Eur J Obstet Gynecol Reprod Biol 2008 Apr;137(2):131-5. Epub 2008 Feb 8 doi: 10.1016/j.ejogrb.2007.12.011. PMID: 18262326
Hanley WB, Lee AW, Hanley AJ, Lehotay DC, Austin VJ, Schoonheyt WE, Platt BA, Clarke JT
Mol Genet Metab 2000 Apr;69(4):286-94. doi: 10.1006/mgme.2000.2985. PMID: 10870846

Diagnosis

Deng IB, Follett J, Bu M, Farrer MJ
Mov Disord 2024 Feb;39(2):249-258. Epub 2023 Nov 28 doi: 10.1002/mds.29677. PMID: 38014588
Thoalnoon OA, Kareem AA, Hammoodi HZ
Arch Razi Inst 2023 Apr;78(2):667-673. Epub 2023 Apr 30 doi: 10.22092/ARI.2022.359480.2431. PMID: 37396747Free PMC Article
Couce ML, Sánchez-Pintos P, Vitoria I, De Castro MJ, Aldámiz-Echevarría L, Correcher P, Fernández-Marmiesse A, Roca I, Hermida A, Martínez-Olmos M, Leis R
Orphanet J Rare Dis 2018 Jun 27;13(1):103. doi: 10.1186/s13023-018-0847-x. PMID: 29945661Free PMC Article
Mitchell JJ, Trakadis YJ, Scriver CR
Genet Med 2011 Aug;13(8):697-707. doi: 10.1097/GIM.0b013e3182141b48. PMID: 21555948
Burnett JR
IDrugs 2007 Nov;10(11):805-13. PMID: 17968763

Therapy

Thoalnoon OA, Kareem AA, Hammoodi HZ
Arch Razi Inst 2023 Apr;78(2):667-673. Epub 2023 Apr 30 doi: 10.22092/ARI.2022.359480.2431. PMID: 37396747Free PMC Article
Li H, Yang H, Li M, Liang L, Zhu H, Chen A, Qian H
BMC Neurol 2022 Nov 4;22(1):409. doi: 10.1186/s12883-022-02946-1. PMID: 36333673Free PMC Article
Jeannesson-Thivisol E, Feillet F, Chéry C, Perrin P, Battaglia-Hsu SF, Herbeth B, Cano A, Barth M, Fouilhoux A, Mention K, Labarthe F, Arnoux JB, Maillot F, Lenaerts C, Dumesnil C, Wagner K, Terral D, Broué P, de Parscau L, Gay C, Kuster A, Bédu A, Besson G, Lamireau D, Odent S, Masurel A, Guéant JL, Namour F
Orphanet J Rare Dis 2015 Dec 15;10:158. doi: 10.1186/s13023-015-0375-x. PMID: 26666653Free PMC Article
Mitchell JJ, Trakadis YJ, Scriver CR
Genet Med 2011 Aug;13(8):697-707. doi: 10.1097/GIM.0b013e3182141b48. PMID: 21555948
Burnett JR
IDrugs 2007 Nov;10(11):805-13. PMID: 17968763

Prognosis

Fang Y, Gao J, Guo Y, Li X, Yuan E, Yuan E, Song L, Shi Q, Yu H, Zhao D, Zhang L
Hum Genomics 2023 Mar 31;17(1):34. doi: 10.1186/s40246-023-00481-9. PMID: 37004080Free PMC Article
Hillert A, Anikster Y, Belanger-Quintana A, Burlina A, Burton BK, Carducci C, Chiesa AE, Christodoulou J, Đorđević M, Desviat LR, Eliyahu A, Evers RAF, Fajkusova L, Feillet F, Bonfim-Freitas PE, Giżewska M, Gundorova P, Karall D, Kneller K, Kutsev SI, Leuzzi V, Levy HL, Lichter-Konecki U, Muntau AC, Namour F, Oltarzewski M, Paras A, Perez B, Polak E, Polyakov AV, Porta F, Rohrbach M, Scholl-Bürgi S, Spécola N, Stojiljković M, Shen N, Santana-da Silva LC, Skouma A, van Spronsen F, Stoppioni V, Thöny B, Trefz FK, Vockley J, Yu Y, Zschocke J, Hoffmann GF, Garbade SF, Blau N
Am J Hum Genet 2020 Aug 6;107(2):234-250. Epub 2020 Jul 14 doi: 10.1016/j.ajhg.2020.06.006. PMID: 32668217Free PMC Article
Rajabi F, Rohr F, Wessel A, Martell L, Dobrowolski SF, Guldberg P, Güttler F, Levy HL
Mol Genet Metab 2019 Dec;128(4):415-421. Epub 2019 Sep 14 doi: 10.1016/j.ymgme.2019.09.004. PMID: 31623983
Jeannesson-Thivisol E, Feillet F, Chéry C, Perrin P, Battaglia-Hsu SF, Herbeth B, Cano A, Barth M, Fouilhoux A, Mention K, Labarthe F, Arnoux JB, Maillot F, Lenaerts C, Dumesnil C, Wagner K, Terral D, Broué P, de Parscau L, Gay C, Kuster A, Bédu A, Besson G, Lamireau D, Odent S, Masurel A, Guéant JL, Namour F
Orphanet J Rare Dis 2015 Dec 15;10:158. doi: 10.1186/s13023-015-0375-x. PMID: 26666653Free PMC Article
Murad H, Dabboul A, Moassas F, Alasmar D, Al-Achkar W
Gene 2013 Oct 10;528(2):241-7. Epub 2013 Jul 12 doi: 10.1016/j.gene.2013.07.001. PMID: 23856132

Clinical prediction guides

Hillert A, Anikster Y, Belanger-Quintana A, Burlina A, Burton BK, Carducci C, Chiesa AE, Christodoulou J, Đorđević M, Desviat LR, Eliyahu A, Evers RAF, Fajkusova L, Feillet F, Bonfim-Freitas PE, Giżewska M, Gundorova P, Karall D, Kneller K, Kutsev SI, Leuzzi V, Levy HL, Lichter-Konecki U, Muntau AC, Namour F, Oltarzewski M, Paras A, Perez B, Polak E, Polyakov AV, Porta F, Rohrbach M, Scholl-Bürgi S, Spécola N, Stojiljković M, Shen N, Santana-da Silva LC, Skouma A, van Spronsen F, Stoppioni V, Thöny B, Trefz FK, Vockley J, Yu Y, Zschocke J, Hoffmann GF, Garbade SF, Blau N
Am J Hum Genet 2020 Aug 6;107(2):234-250. Epub 2020 Jul 14 doi: 10.1016/j.ajhg.2020.06.006. PMID: 32668217Free PMC Article
Jeannesson-Thivisol E, Feillet F, Chéry C, Perrin P, Battaglia-Hsu SF, Herbeth B, Cano A, Barth M, Fouilhoux A, Mention K, Labarthe F, Arnoux JB, Maillot F, Lenaerts C, Dumesnil C, Wagner K, Terral D, Broué P, de Parscau L, Gay C, Kuster A, Bédu A, Besson G, Lamireau D, Odent S, Masurel A, Guéant JL, Namour F
Orphanet J Rare Dis 2015 Dec 15;10:158. doi: 10.1186/s13023-015-0375-x. PMID: 26666653Free PMC Article
Couce ML, Guler I, Anca-Couce A, Lojo M, Mirás A, Leis R, Pérez-Muñuzuri A, Fraga JM, Gude F
Eur J Pediatr 2015 May;174(5):651-9. Epub 2014 Nov 1 doi: 10.1007/s00431-014-2446-8. PMID: 25367055
Campistol J, Gassió R, Artuch R, Vilaseca MA; PKU Follow-up Unit
Dev Med Child Neurol 2011 May;53(5):405-8. Epub 2011 Mar 21 doi: 10.1111/j.1469-8749.2010.03869.x. PMID: 21418193
Porta F, Mussa A, Zanin A, Greggio NA, Burlina A, Spada M
J Pediatr Gastroenterol Nutr 2011 Mar;52(3):345-50. doi: 10.1097/MPG.0b013e3182093b32. PMID: 21336059

Recent systematic reviews

Luengo-Pérez LM, Fernández-Bueso M, Guzmán-Carmona C, López-Navia A, García-Lobato C
Nutrients 2024 Jun 11;16(12) doi: 10.3390/nu16121833. PMID: 38931188Free PMC Article
Rostampour N, Chegini R, Hovsepian S, Zamaneh F, Hashemipour M
Neurol Sci 2022 Sep;43(9):5593-5603. Epub 2022 Jun 21 doi: 10.1007/s10072-022-06194-6. PMID: 35729439
Ilgaz F, Pinto A, Gökmen-Özel H, Rocha JC, van Dam E, Ahring K, Bélanger-Quintana A, Dokoupil K, Karabulut E, MacDonald A
Nutrients 2019 Sep 3;11(9) doi: 10.3390/nu11092070. PMID: 31484352Free PMC Article
Zschocke J
Hum Mutat 2003 Apr;21(4):345-56. doi: 10.1002/humu.10192. PMID: 12655544

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    • ACMG ACT, 2022
      American College of Medical Genetics and Genomics, Newborn Screening ACT Sheet, Elevated Phenylalanine, Phenylalanine hydroxylase deficiency (PAH), 2022
    • ACMG Algorithm, 2022
      American College of Medical Genetics and Genomics, Algorithm, PAH deficiency: Elevated Phenylalanine, 2022

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