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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

Himmelreich N, Shen N, Okun JG, Thiel C, Hoffmann GF, Blau N
Mol Genet Metab 2018 Sep;125(1-2):86-95. Epub 2018 Jun 23 doi: 10.1016/j.ymgme.2018.06.011. PMID: 30037505
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
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

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
Erdol S, Bilgin H
J Pediatr Endocrinol Metab 2022 Apr 26;35(4):463-467. Epub 2022 Jan 27 doi: 10.1515/jpem-2021-0737. PMID: 35084144
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
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

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
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
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

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
Verduci E, Moretti F, Bassanini G, Banderali G, Rovelli V, Casiraghi MC, Morace G, Borgo F, Borghi E
Nutr Metab Cardiovasc Dis 2018 Apr;28(4):385-392. Epub 2018 Jan 31 doi: 10.1016/j.numecd.2018.01.004. PMID: 29502926
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
Vieira Neto E, Laranjeira F, Quelhas D, Ribeiro I, Seabra A, Mineiro N, Carvalho LM, Lacerda L, Ribeiro MG
Mol Genet Genomic Med 2019 May;7(5):e610. Epub 2019 Mar 3 doi: 10.1002/mgg3.610. PMID: 30829006Free PMC Article
Muntau AC, Röschinger W, Habich M, Demmelmair H, Hoffmann B, Sommerhoff CP, Roscher AA
N Engl J Med 2002 Dec 26;347(26):2122-32. doi: 10.1056/NEJMoa021654. PMID: 12501224

Clinical prediction guides

Randell NJS, Barker-Collo SL, Murrell K, Wilson C
N Z Med J 2022 Dec 16;135(1567):31-42. PMID: 36521084
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
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
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
Levy HL, Waisbren SE, Lobbregt D, Allred E, Leviton A, Koch R, Hanley WB, Rouse B, Matalon R, de la Cruz F
Eur J Pediatr 1996 Jul;155 Suppl 1:S20-5. doi: 10.1007/pl00014243. PMID: 8828603

Recent systematic reviews

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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