CONDITIONS & DISORDERS
PHENYLKETONURIA: A LIFE-LONG JOURNEY Phenylketonuria (PKU) is a rare inherited error of metabolism caused by a deficiency in the enzyme phenylalanine hydroxylase (PAH).1 Loss of this enzyme results in mental retardation and organ damage. A low-protein diet for life is the mainstay of treatment and is especially important in maternal PKU, which can severely compromise pregnancy. PKU affects around 1 in 10,000 babies born in the UK every year, with males and females equally affected. Globally, PKU varies amongst ethnic groups, races and geographic regions.3 It is an autosomal recessive disorder, meaning an individual needs two copies of the mutant gene that causes PKU.5 The human gene for PAH is located at chromosome 12q23.2, and more than 600 mutations of the PAH gene have been reported by scientists.5,6,7 If both parents are carriers of a mutant gene, then there is a one-in-four chance of the child being affected by PKU. PAH is responsible for the conversion of phenylalanine (Phe) into tyrosine and other by-products (see Figure 1). Its deficiency, if untreated, results in the accumulation of Phe in the body, which can cause irreversible brain damage.1,2 PKU was first described by Norwegian physician Dr Asbjørn Følling in 1934.1,2,3 He found higher levels of phenylpyruvic acid, an intermediate product of Phe metabolism, in the urine
of intellectually impaired individuals and thus named the disease. In 1969, the universal screening programme for the early detection of PKU was introduced in several developed countries including the UK, Europe and the USA.8 It is a simple heel prick test performed in the first 24-72 hours after birth. Dried blood spots are the best sample for the simultaneous measurement of Phe, pterins and dihydropterin reductase activity from a single specimen.4,5 LEVELS AND SYMPTOMS
There is no specific classification of PKU. Nevertheless, on the basis of PAH activity levels and blood Phe levels on diagnosis or when untreated, it is divided into three types: • Classic PKU is when PAH is completely missing and Phe levels are 1200µmol/L or above.9,10 • Moderate PKU is caused by residual enzyme activity (Phe levels are 900-1200µmol/L). • Mild PKU is when Phe concentration is 600-900µmol/L.
Dr Shazia Faisal ANutr Shazia is a Medical Doctor with a special interest in metabolic and lifestyle medicine. She is a Community Nutritionist and a Nutritional Blogger.
REFERENCES Please visit: nhdmag.com/ references.html
Figure 1: Phenylalanine metabolism inside the human body
Dietary protein Phenylpyruvic acid
Phenylalanine
Tyrosine
Phenylketonuria
Melanin
Proteins
Dopamine
www.NHDmag.com February 2021 - Issue 160
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