Amish, Mennonite, and Hutterite
Genetic Disorder Database

Phenylketonuria

Disorder
OMIM #: #261600  (Click to access OMIM database)
Disorder: Phenylketonuria 
Also known as: PKU, PHENYLALANINE HYDROXYLASE DEFICIENCY, PAH DEFICIENCY, OLIGOPHRENIA PHENYLPYRUVICA, FOLLING DISEASE, PHENYLALANINE HYDROXYLASE, INCLUDED
PAH, INCLUDED, PKU1, INCLUDED, HYPERPHENYLALANINEMIA, MILD, INCLUDED
HPA, INCLUDED, PHENYLALANINEMIA, INCLUDED 
Clinical
Phenotype: deficiency of phenylalanine hydroxylase, high levels of plasma phenylalanine, developmental delay/mental retardation, vomiting, eczema, seizures, behavioural problems, urine smells "musky" 
Seen In: Amish
Old Order Mennonite
Old Colony Mennonite
Unknown/Other Mennonite
Hutterite
Remarks:  
Mutations
1   Amish  
Gene: PAH
Base Change: c.168+5G>C
Amino Acid Change: splicing defect
2   Amish, Old Order Mennonite  
Gene: PAH
Base Change: G>A, at nucleotide 782
Amino Acid Change: arg 261 --> gln
3   Amish  
Gene: PAH
Base Change: c.284_286delTCA
Amino Acid Change: p.Ile95del
4   Amish, Old Order Mennonite  
Gene: PAH
Base Change: c.1315+1G>A
Amino Acid Change: splicing defect
5   Amish  
Gene: PAH
Base Change: c.1066-11G>A
Amino Acid Change: splicing defect
Last updated: 2018-07-20 

References
Abadie V, Lyonnet S, Maurin N, Berthelon M, Caillaud C, Giraud F, Mattei J.-F, Rey J, Rey F, and Munnich A. (1989) CpG dinucleotides are mutation hot spots in phenylketonuria. Genomics 5: 936-939.
PubMed ID: 2574153 
Caillaud C, Lyonnet S, Rey F, Melle D, Frebourg T, Berthelon M, Vilarinho L, Vaz Osorio R, Rey J, and Munnich A. (1991) A 3-base pair in-frame deletion of the phenylalanine hydroxylase gene results in a kinetic variant of phenylketonuria. J Biol Chem 266(15): 9351-9354.
PubMed ID: 1709636 
Dworniczak B, Aulehla-Scholz C, Kalaydjieva L, Bartholome K, Grudda K, and Horst J. (1991) Aberrant splicing of phenylalanine hydroxylase mRNA: the major cause for phenylketonuria in parts of southern Europe. Genomics 11: 242-246.
PubMed ID: 1769645 
Schwoerer JS, Drilias N, Kuhl A, Mochal S, Baker M. (2018) Genotypes of patients with phenylalanine hydroxylase deficiency in the Wisconsin Amish. Mol Genet Metab Rep Mar 8;15:75-77.
PubMed ID: 29560316 
Strauss KA, Puffenberger EG. (2009) Genetics, medicine, and the Plain people. Annu Rev Genomics Hum Genet 10:513-36.
PubMed ID: 19630565 
Wang H, Nye L, Puffenberger E, Morton H. (2007) Phenylalanine hydroxylase deficiency exhibits mutation heterogeneity in two large old order Amish settlements. Am J Med Genet A 143A(16):1938-40.
PubMed ID: 17630668 

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