Here I present: “Phenylketonuria”, Victor McKusick, Mendelian Inheritance in Man’, 1966. 苯基酮尿症。(PKU).
INTRODUCTION.
Phenylketonuria (PKU) is an inborn error of metabolism that results in decreased metabolism of the amino acid phenylalanine. Untreated PKU can lead to intellectual disability, seizures, behavioral problems, and mental disorders. 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 small head, and low birth weight.
A classification scheme proposed was intended to simplify the nomenclature. In this system:
- Phenylketonuria (PKU) is the most severe of the three types and in an untreated state is associated with plasma Phe concentrations >1,000 µmol/L and a dietary Phe tolerance of <500 mg/day. PKU is associated with a high risk of severely impaired cognitive development.
- Hyperphenylalaninemia (HPA) is associated with plasma Phe concentrations consistently above normal (i.e., >120 µmol/L) but lower than 1,000 µmol/L when an individual is on a normal diet’. Individuals with non-PKU HPA are at a much lower risk for impaired cognitive development in the absence of treatment.
- Variant PKU includes those individuals who do not fit the description for either PKU or HPA.
There is evidence phenylketonuria (PKU) and hyperphenylalaninemia (HPA) are caused by homozygous or compound heterozygous mutations in the phenylalanine hydroxylase (PAH) gene on chromosome 12q23.2 and genomic coordinates 12:102,836,889-102,958,441. The screenshot of the PAH gene 121,553 bp (base pairs) of DNA sequence length is shown BELOW. Nine (9) other genes besides PAH in the 12q23.2 cytogenetic location are listed BENEATH.
| Coordinate | Symbol | Genomic Name |
| 12:102,073,103 | NUP37 | Nucleoporin, 37kD |
| 12:102,120,183 | C12orf48 | Chromosome 12 open reading frame 48 |
| 12:102,196,459 | PMCH | Pro-melanin-concentrating hormone |
| 12:102,395,874 | IGF1 | Insulin-like growth factor-1, or somatomedin |
| 12:102,836,889 | PAH | Phenylalanine hydroxylase |
| 12:102,957,674 | ASCL1 | Achaete-scute family bHLH factor 1 |
| 12:103,587,273 | STAB2 | Stabilin 2 |
| 12:103,746,315 | NT5DC3 | 5′ nucleotidase domain-containing protein 3 |
| 12:103,930,410 | HSP90B1 | Heat-shock protein, 90kD, beta, 1 |
| 12:103,950,194 | C12orf73 | Chromosome 12 open reading frame 73 |
