Team:NWU-China/Description
Background & Inspiration
Have you ever noticed that there are some people whose skin is white, body smells musty. They can’t eat the mother's milk after birth. What's more, they can't eat normal food as we do. As a result, they are called 'angels who don't eat human food'. They are patients with phenylketonuria. Untreated phenylketonuria is associated with progressive intellectual impairment, accompanied by a constellation of additional symptoms, which can include eczematous rash, autism, seizures, and motor deficits. Developmental problems, aberrant behavior, and psychiatric symptoms often become apparent as the child grows. (Anita MacDonald et al., 2000)
Phenylketonuria (PKU) is one of the few treatable congenital metabolic disorders among many birth defects. Phenylalanine hydroxylase (PAH) converts phenylalanine into tyrosine and requires the cofactor tetrahydrobiopterin (BH4), molecular oxygen, and iron to do so. Loss of PAH activity results in increased concentrations of phenylalanine in the blood and toxic concentrations in the brain. PKU is due to the deficiency of enzymes in the metabolic pathway of phenylalanine (Phe), which prevents phenylalanine from being transformed into tyrosine(Tyr), resulting in the accumulation of phenylalanine and keto acid, and the accumulation of abnormal metabolites in the body, which damages the brain and nervous system. It is excreted from urine in large quantities.(Prof Nenad et al., 2010)
Huang Shangzhi, a professor at the Chinese Academy of Medical Sciences, said that the screening coverage of phenylketonuria in China was only 20%. The official incidence of PKU was about 1/11,000, with a total population of about 40,000.
*Data From NCBI.
*Data From Ministry of Health of PRC.
Three days after the birth of the newborn. The cut-off value of Phe is 1.8mg/dL (by the equivalent of 108μmol/L). When phe>1.8mg/dL twice, it will be diagnosed as hyperphenylalaninemia (HPA). Differential diagnosis of HPA is aimed to identify PHA deficiency PKU and tetrahydrobiopterin deficiency (BH4D) which are also known as the classical type and non-classical one. After excluding BH4D of HPA, Phe>360μmol/L is PKU,Phe≤360μmol/L is HPA. The Phe in blood of normal people was 0.06 ±0.18 mmol/L (1: 3 mg/dl), and that of patients with Phe was 1.2 mmol/L (20 mg/dl).(Moat et al., 2019)
In the treatment of PKU, the classical type should strictly limit the intake of food containing phenylpyruvate, that is, low-phenylalanine diet therapy. The non-classical type was mainly supplemented with tetrahydrobiopterin (BH4).
Low phenylalanine diet therapy is mainly suitable for typical PKU and patients whose blood phenylalanine level is continuously higher than 1.22 mmol/L (20mg/dl). Because phenylalanine is an essential amino acid for protein synthesis and can cause nervous system damage when it is totally deficient, infants can be fed special low-phenylalanine milk powder. Starch, vegetables, fruits and other low-protein foods should be the main supplementary food in early childhood. The requirement of phenylalanine for children is about 50-70 mg/(kg.d) within 2 months, 40 mg/(kg.d) within 3-6 months, 25-30 mg/(kg.d) at 2 years old and 10-30 mg/(kg.d) above 4 years old. It is advisable to maintain the concentration of phenylalanine in blood at 0.12-0.6 mmol/L (2-10 mg/dl). (Hiu Man et al., 2019)
*Data From NCBI
The aim of dietary therapy is to keep phenylalanine in blood at 0.24-0.6 mmol/L. Children can be fed low-phenylalanine food supplemented by breast milk and milk.
Phenylalanine is 40 mg per 100 ml of breast milk and 50 mg per 30 ml of milk. Specialty foods that limit the intake of phenylalanine are expensive and difficult to operate. There is no consensus as to when the dietary treatment to limit the intake of phenylalanine in the diet should be stopped, and it is generally believed that it should be maintained for 10 years. At the same time of limiting the dietary treatment of phenylalanine intake, supplementation of tyrosine or replacement of diet with supplementation of tyrosine.
Dietary tyrosine supplementation can restore hair pigmentation to normal, but does no effect on intellectual progress. In the course of dietary treatment to restrict the intake of phenylalanine, the nutritional status of growth and development, the level of phenylalanine in blood and its side effects should be closely observed. The main side effects are other nutritional deficiencies, such as diarrhea, anemia (macrocytosis), hypoglycemia, hypoproteinemia and nicotinic acid deficiency-like rash.
Inspection methods:
1.Urine ferric chloride experiment
It is used in screening for older infants and children. Drop FeCl3 into urine, if it turns into green ,the results is positive, which indicates Phe concentration in urine is increasing.(Chieh Lin et al. 2018)
2. Plasma amino acid analysis and urine organic acid analysis
It can provide biochemical diagnosis basis for this disease, meanwhile, it can also differentiate other amino acid and organic acid metabolic diseases.
3.Analysis of uroterin
The contents of urine miopterin and bioterin were determined by high pressure liquid chromatography.