Reference Guide · PKU

PKU Glossary:
Medical Terms Explained

Every medical term related to Phenylketonuria (PKU) — from A for Amino Acid to X for Xylitol — explained in plain language. For patients, parents, and anyone who wants to understand PKU.

60+ Terms Alphabetical Order Medically Reviewed PKU-Specific
A
Amino Acid Medical
The molecular building blocks of all proteins. There are 20 different amino acids, of which 9 are essential — the body cannot produce them independently and they must be obtained through food or supplementation. In PKU, amino acid intake must be carefully balanced because all natural dietary protein contains phenylalanine. Essential amino acids are supplied through phenylalanine-free amino acid formula.
Amino Acid Formula (PKU Formula) Medical
Phenylalanine-free medical formula that provides all essential amino acids, vitamins, minerals, and trace elements that cannot be obtained from the severely restricted natural protein intake. Available as powder, ready-to-drink solutions, tablets, gel, or bars. A daily non-negotiable component of every PKU treatment plan. Manufacturers include Nutricia, Vitaflo, Cambrooke, and Milupa.
Autosomal Recessive Medical
An inheritance pattern in which both copies of a gene — one inherited from each parent — must carry the disease-causing mutation for the condition to manifest. PKU follows this pattern: parents are typically healthy, symptom-free carriers (heterozygous). When both parents are carriers, each child has a 25% chance of having PKU, a 50% chance of being a carrier, and a 25% chance of being unaffected.
B
BH4 (Tetrahydrobiopterin) Medical
The natural cofactor of the enzyme phenylalanine hydroxylase (PAH). BH4 deficiency can independently cause severe hyperphenylalaninaemia with neurological symptoms and must be distinguished from classical PAH deficiency. As a synthetic drug (sapropterin / Kuvan®), BH4 can significantly increase phenylalanine tolerance in approximately 20–30% of PKU patients; effectiveness is assessed via a BH4 loading test over 24–48 hours.
Biopterin Medical
A precursor of BH4 (tetrahydrobiopterin). Biopterin levels in urine and blood are measured to differentiate between BH4 synthesis disorders and classical PAH deficiency. Normal biopterin combined with elevated blood Phe indicates classical PKU; elevated neopterin alongside elevated Phe suggests a BH4 metabolic defect.
Blood Phe Level Medical
The concentration of phenylalanine in the blood, measured in µmol/L (normal range without PKU: 35–120 µmol/L). The most important monitoring parameter in PKU management. Target values per EU guidelines 2017: children and adults ≤ 360 µmol/L; pregnant women ≤ 120 µmol/L. Measured via dried blood spot (fingertip) or venous blood draw.
BLS Food Database App
German national food composition database (Bundeslebensmittelschlüssel) containing precise phenylalanine values for over 15,000 foods. Version BLS 4.0 is the current gold standard for PKU dietary planning. PHE Buddy integrates BLS 4.0 in full, providing accurate Phe data for Germany, Austria, and Switzerland.
C
Catabolism / Catabolic State Medical
The breakdown of body tissues — particularly muscle protein — during illness, fever, prolonged fasting, or physical stress. In PKU, catabolism releases phenylalanine from degraded body protein, causing a transient rise in blood Phe levels. During infections, especially close monitoring and adequate caloric intake are therefore essential.
Chromosome 12 Medical
The PAH gene is located on chromosome 12 (precisely: 12q23.2). Mutations in this gene cause PKU and mild hyperphenylalaninaemia. Over 1,000 different disease-causing PAH variants are known; the most common in Central Europe is p.Arg408Trp, typically associated with classical PKU.
Classical PKU Medical
The most severe form of phenylketonuria: untreated blood Phe > 1,200 µmol/L, with near-zero PAH residual activity. Requires the strictest dietary restriction and rarely responds to BH4 therapy. Untreated classical PKU results in severe intellectual disability, microcephaly, epilepsy, and behavioural disorders. With newborn screening and consistent treatment, fully normal development is achievable.
Compliance (Treatment Adherence) Medical
The consistent adherence to the prescribed PKU diet and amino acid formula recommendations. Good compliance is crucial for stable blood Phe levels and healthy cognitive development. It is especially challenging during adolescence and early adulthood; PHE Buddy reminder features can support day-to-day adherence.
D
DESIREE Registry Medical
European PKU Patient Registry (Development of a European Registry and Network for Inherited Metabolic Diseases), collecting anonymised long-term data on PKU patient outcomes, treatment, and natural history from across Europe. Provides the evidence base for current clinical guidelines; administered by the IMD Institute in Barcelona.
Dietitian / Registered Dietitian Medical
A healthcare professional specialised in nutritional therapy for PKU, trained to calculate and plan individual phenylalanine daily allowances. Prepares formula prescriptions, educates patients and families, and supports major life transitions (childhood to adulthood, pregnancy planning). A core member of the multidisciplinary team at any metabolic centre.
Dried Blood Spot (DBS) Medical
Home blood sampling method: a drop of capillary blood from the fingertip (using a lancet) is placed on a special filter card, allowed to dry, and mailed to the laboratory. The standard method for regular home monitoring of blood Phe in PKU. Laboratory results are typically available within 24–48 hours.
E
Enzyme Medical
A biological catalyst — a protein that accelerates biochemical reactions in the body without being consumed in the process. In PKU, the enzyme phenylalanine hydroxylase (PAH) is defective or absent, meaning phenylalanine cannot be converted into tyrosine and accumulates to dangerous levels in the blood and brain.
ESPKU Medical
European Society for Phenylketonuria and Allied Disorders Treated as Phenylketonuria. The European umbrella organisation of PKU patient associations. Played a key role in developing the comprehensive 2017 EU PKU guidelines and is a vital advocacy body and information resource for people affected by PKU (espku.org).
Exchange Unit (EU) / Phe Exchange Abbreviation
A dietary measurement unit used in PKU meal planning: 1 exchange unit always equals 50 mg of phenylalanine, regardless of the food or portion size. Simplifies daily Phe calculation considerably — for example, a food portion containing 100 mg Phe equals 2 exchange units. PHE Buddy converts automatically between exchange units and milligrams.
F
Ferritin Medical
An iron-storage protein measured in blood to assess iron status. In PKU patients, ferritin can be low due to restricted intake of iron-rich foods (meat, fish, legumes). Annual laboratory monitoring is recommended; iron supplementation may be necessary. Well-formulated phenylalanine-free amino acid formulas contain iron.
Folic Acid (Vitamin B9) Medical
A water-soluble B vitamin essential for cell division and DNA synthesis. Of particular importance in maternal PKU: a minimum of 5 mg folic acid daily before and throughout pregnancy to prevent neural tube defects. Most PKU amino acid formulas contain folic acid; when formula intake is insufficient, adequate intake must be verified.
G
GDPR / Data Privacy (PHE Buddy) App
PHE Buddy processes sensitive health data — blood Phe values, dietary logs, formula intake records — in full compliance with the EU General Data Protection Regulation (GDPR). Data is stored encrypted, never sold to third parties, and users retain full control over their own data at all times.
Genotype Medical
The genetic makeup of an individual — in PKU specifically, the combination of the two PAH alleles (gene variants) inherited from each parent. The genotype largely determines clinical severity and the likelihood of responding to BH4 therapy. Compound heterozygosity (two different pathogenic variants) is more common in PKU than homozygosity (the same mutation on both chromosomes).
GMP (Glycomacropeptide) Medical
A naturally phenylalanine-low whey protein derivative (caseinomacropeptide) used as the basis for PKU specialty products (e.g. PKU Sphere by Vitaflo). Compared to classical amino acid formulas, GMP-based products often offer a more palatable taste, greater satiety, and a more favourable insulin response, while providing a small amount of naturally occurring amino acids.
H
Heelstick Medical
The standard blood sampling method used in newborn screening. A small drop of capillary blood is taken from the heel of the newborn and applied to a filter paper card (Guthrie card). The sample is sent to a laboratory where tandem mass spectrometry screens for more than 25 metabolic disorders including PKU.
Homozygous Medical
A genetic state in which both alleles of a gene are identical — meaning the same PAH mutation was inherited from both parents. In contrast, heterozygous describes having two different alleles; compound heterozygous describes having two different disease-causing mutations. Homozygous PKU patients often — but not always — have more severe disease courses.
Hyperphenylalaninaemia (HPA) Medical
The umbrella term for all conditions with persistently elevated blood phenylalanine above 120 µmol/L. Classified by severity: classical PKU (> 1,200 µmol/L untreated), mild PKU (600–1,200 µmol/L), mild HPA (120–600 µmol/L). The cause may be a PAH deficiency (most common), a BH4 metabolic defect, or other rare enzyme deficiencies.
I
ICD-10 E70.0 Abbreviation
The International Classification of Diseases (10th revision) diagnostic code for Phenylketonuria (PKU), as defined by the WHO. Required for medical letters, insurance correspondence, and prescription writing. Related codes: E70.1 = Mild hyperphenylalaninaemia; E70.8 = Other disorders of aromatic amino-acid metabolism.
Iodine in PKU Medical
An essential trace element that can be insufficient in PKU patients due to restricted intake of iodine-rich foods (seafood, dairy products, iodised salt). Iodine deficiency can lead to thyroid dysfunction; thyroid function should be checked at annual metabolic reviews. Well-formulated amino acid formulas contain iodine; inadequate formula intake warrants monitoring.
Isoleucine Medical
An essential branched-chain amino acid (BCAA) included in phenylalanine-free amino acid formulas. Isoleucine contains no phenylalanine and requires no restriction in PKU. It plays an important role in muscle metabolism, immune function, and energy production during physical activity.
K
Kuvan® Medical
The brand name for sapropterin dihydrochloride (synthetic BH4), manufactured by BioMarin Pharmaceutical. Approved for the treatment of BH4-responsive PKU and hyperphenylalaninaemia. Taken orally as a soluble tablet; approved from one month of age. Effective in approximately 20–30% of PKU patients, predominantly those with mild to moderate disease.
L
Leucine Medical
An essential branched-chain amino acid (BCAA) present in PKU amino acid formulas. Leucine contains no phenylalanine and is not restricted in PKU. It is important for muscle protein synthesis, energy supply during exercise, and regulation of insulin signalling.
Liver Medical
The primary site of phenylalanine hydroxylation: the PAH enzyme is active exclusively in hepatocytes (liver cells). This is why even a healthy liver's temporary dysfunction can raise Phe levels in non-PKU patients. Gene therapy approaches for PKU aim to introduce a functional copy of the PAH gene into liver cells to restore enzymatic activity.
Low-Protein Products (LP Products) Medical
Specially manufactured dietary foods with very low protein content and therefore very low phenylalanine values: LP bread, LP pasta, LP flour, LP rice, LP biscuits. They allow for a significantly more varied and everyday diet in PKU. In Germany, Austria, and Switzerland, LP products are generally available on prescription and reimbursed by health insurance.
M
Maternal PKU Medical
PKU in pregnant women. Elevated maternal blood Phe levels have a teratogenic effect on the unborn child: congenital heart defects, microcephaly, intrauterine growth restriction, and cognitive impairment are among the consequences. A strict low-Phe diet (target: Phe < 120 µmol/L) should ideally begin before conception and be maintained throughout the entire pregnancy.
Metabolic Centre Medical App
A specialist medical centre for inherited metabolic disorders including PKU. A multidisciplinary team of metabolic physicians, dietitians, psychologists, and laboratory specialists provides treatment, monitoring, and counselling. Regular appointments are recommended: at least annually for stable adults, more frequently for children, adolescents, and pregnant women. PHE Buddy links a list of metabolic centres in Austria, Germany, and Switzerland.
Methionine Medical
A sulphur-containing essential amino acid included in phenylalanine-free amino acid formulas. Methionine contains no phenylalanine and is not restricted in PKU. It is essential for glutathione synthesis (the body's primary antioxidant defence) and important methylation reactions throughout the body.
Mild HPA (Hyperphenylalaninaemia) Medical
Untreated blood Phe between 120 and 600 µmol/L. Usually no compulsory treatment is required, as severe cognitive consequences are not expected at these levels; however, regular lifelong monitoring remains important. During pregnancy, the same strict Phe targets apply as for classical PKU.
Mild PKU Medical
Untreated blood Phe between 600 and 1,200 µmol/L. Less strict dietary restriction than classical PKU; individual Phe tolerance is higher. BH4 response is more common than in classical PKU. Regular monitoring remains lifelong, particularly important when pregnancy is planned or occurs.
Monitoring App
Regular measurement of blood Phe levels and assessment of nutritional and laboratory status. Recommended frequency per EU guidelines: 1–2 times weekly for children under 12 and pregnant women; 1–2 times monthly for stable adults. PHE Buddy provides digital tracking, trend graphs, and reminders for dried blood spot testing.
N
Neopterin Medical
A biomarker measured in urine and blood, used to differentiate between PAH deficiency and BH4 synthesis disorders. Elevated neopterin alongside elevated Phe suggests a BH4 metabolic defect (e.g. GTPCH or PTPS deficiency); normal neopterin with elevated Phe indicates classical PAH-deficiency PKU. Part of the initial diagnostic workup for every case of hyperphenylalaninaemia.
Newborn Screening Medical
Mandatory for all newborns in Germany, Austria, and Switzerland. A blood test on day 2–3 of life, taken from the heel (heelstick) onto a filter card. Analysed by tandem mass spectrometry for more than 25 metabolic disorders including PKU. Enables PKU diagnosis and treatment initiation before any clinical symptoms appear, preventing irreversible harm.
Norvaline Medical
A non-proteinogenic amino acid found naturally in some plants. Not directly relevant in PKU management; norvaline is occasionally discussed as a potential trace contaminant in amino acid mixtures. Manufacturers of PKU formulas routinely test and control their products for such unwanted components.
O
Orphan Drug Medical
EU designation for medicines targeting rare diseases (< 5 affected individuals per 10,000 people in the population). PKU medications including sapropterin (Kuvan®) and pegvaliase (Palynziq®) hold orphan drug status from the European Medicines Agency (EMA). The designation enables streamlined regulatory approval, extended market exclusivity, and research funding support.
P
PAH (Phenylalanine Hydroxylase) Medical Abbreviation
The enzyme that converts phenylalanine (Phe) into tyrosine using the cofactor BH4. In PKU, PAH is defective or absent. The PAH gene is located on chromosome 12q23.2; over 1,000 disease-causing variants are known. The residual PAH activity (0–100% of normal) largely determines the clinical phenotype, from classical PKU to mild HPA.
PAL (Phenylalanine Ammonia-Lyase) Medical Abbreviation
An enzyme derived from plants and bacteria that converts phenylalanine into trans-cinnamic acid and ammonia via a completely different pathway — one that requires neither BH4 nor PAH. This principle is the basis for the drug pegvaliase (Palynziq®), which bypasses the defective PAH enzyme entirely to reduce blood Phe levels.
Palynziq® Medical
Brand name for pegvaliase (BioMarin Pharmaceutical). Approved in the EU since 2019 for adults (aged ≥ 16 years) with PKU who do not respond adequately to BH4 treatment. Administered as a daily subcutaneous (under-skin) injection. Dose titration takes approximately 12 months and requires regular medical supervision for hypersensitivity reactions.
Pegvaliase Medical
A recombinant, PEGylated phenylalanine ammonia-lyase (PAL) that converts phenylalanine to trans-cinnamic acid and ammonia — a metabolic pathway entirely independent of PAH. Demonstrated significant blood Phe reduction in clinical trials (PRISM programme). Common side effects include injection-site reactions, joint pain, and hypersensitivity reactions. Brand name: Palynziq®.
Phe (Phenylalanine) Abbreviation
An essential aromatic amino acid (C₉H₁₁NO₂) present in all natural dietary proteins — on average approximately 2.6–9% of the protein content. In PKU patients, Phe intake is strictly limited: depending on individual tolerance, 200–1,000 mg of Phe per day. Expressed in milligrams (mg) or exchange units (EU, where 1 EU = 50 mg Phe) in dietary planning.
Phe Tolerance Medical
The individual maximum daily amount of phenylalanine a PKU patient can consume without exceeding their blood Phe target range. Tolerance varies greatly depending on genotype, age, body weight, and current health status — for example, it decreases noticeably during infections or illness.
PHE Buddy App
The PKU app for phenylalanine tracking with BLS 4.0 food database (15,000+ entries), amino acid formula logging, blood Phe documentation, and trend graphs. Free for iOS and Android. Developed by PCM Solution GmbH, Eben im Pongau, Austria.
Phenylketonuria (PKU) Medical
An inherited metabolic disorder following an autosomal recessive pattern. A defect in the enzyme phenylalanine hydroxylase (PAH) leads to the accumulation of phenylalanine in the blood and brain. Frequency: approximately 1 in 10,000 births in Central Europe. Untreated: severe intellectual disability, epilepsy, behavioural disorders. With newborn screening and consistent treatment: fully normal development is achievable.
Phenylpyruvic Acid (Phenylpyruvate) Medical
A metabolite excreted in the urine when blood Phe levels are persistently elevated. Its urinary excretion gave PKU its historical name "phenylpyruvic oligophrenia" (Fölling, 1934). Phenylpyruvate is neurotoxic and contributes to the brain damage seen in untreated PKU. It also causes the characteristic musty or mousy odour associated with undiagnosed PKU.
Protein Medical
A macronutrient composed of amino acids, containing approximately 2.6–9% phenylalanine in natural foods depending on the source. In PKU, natural protein intake must be severely restricted (depending on individual tolerance: 5–15 g/day). All remaining protein requirements are met by phenylalanine-free amino acid formula.
R
Residual Activity (PAH) Medical
The remaining enzymatic activity of the PAH enzyme in PKU patients, expressed as a percentage of the healthy norm. It largely determines disease severity: 0% residual activity = classical PKU; 1–3% = mild PKU; > 3% = mild HPA. Residual PAH activity also correlates with BH4 response: higher residual activity = more likely BH4 response.
Prescription / Medical Prescription Medical
PKU amino acid formula and low-protein (LP) products are prescribed by physicians in Germany, Austria, and Switzerland and reimbursed by statutory health insurance. The prescribing clinician is usually the metabolic specialist at the treating centre. Prescriptions must be renewed regularly to maintain supply continuity.
S
Sapropterin (BH4) Medical
Synthetic tetrahydrobiopterin (BH4), an oral cofactor of the PAH enzyme. Brand name: Kuvan® (BioMarin). Taken as a soluble tablet. Effective in approximately 20–30% of PKU patients (predominantly mild to moderate disease); can increase Phe tolerance by a factor of 2 to 3. A BH4 loading test is required before initiating therapy to confirm responsiveness.
Screening Medical
See Newborn Screening. Generally: the systematic examination of an entire population group for a condition before symptoms develop. The PKU newborn screening programme is one of the most successful screening initiatives in medical history, having prevented severe intellectual disability in hundreds of thousands of people worldwide.
Selenium in PKU Medical
An essential trace element with antioxidant function (component of glutathione peroxidase). Selenium levels can be low in PKU patients due to restricted intake of selenium-rich foods (meat, fish, legumes). Well-formulated amino acid formulas contain selenium; when formula intake is inadequate, selenium status should be monitored via annual blood tests.
T
Tandem Mass Spectrometry (Tandem-MS) Medical
A high-throughput analytical method for simultaneously measuring amino acids and acylcarnitines from minimal blood samples (dried blood spots). The gold standard for newborn screening and PKU follow-up monitoring. A single blood spot can simultaneously detect more than 25 inherited metabolic disorders.
Target Value (Blood Phe Target) Medical App
The recommended blood Phe concentration per EU PKU guidelines 2017: children aged 0–12 years ≤ 120–240 µmol/L (age-dependent); adolescents and adults ≤ 360 µmol/L; pregnant women ≤ 120 µmol/L. The treating metabolic specialist may set individual targets based on clinical judgement. PHE Buddy displays personal target ranges in the dashboard and highlights out-of-range values.
Tyr (Tyrosine) Abbreviation
A non-essential amino acid normally synthesised from phenylalanine. In PKU this conversion is blocked, meaning tyrosine levels are often low in affected individuals — making tyrosine "conditionally essential". Amino acid formulas therefore include tyrosine as a supplement. Tyrosine is a precursor to dopamine, adrenaline, noradrenaline, melanin, and thyroid hormones.
U
Urinary Phenylalanine Medical
Measurement of phenylalanine in the urine as an alternative monitoring approach. Less precise than blood Phe, since urinary Phe is heavily influenced by hydration status, kidney function, and time of collection. Rarely used for routine follow-up monitoring; the dried blood spot test remains the gold standard for home monitoring in PKU.
V
Valine Medical
An essential branched-chain amino acid (BCAA) present in phenylalanine-free amino acid formula. Valine contains no phenylalanine and is not restricted in PKU. It plays a key role in tissue regeneration, immune function, and energy metabolism, particularly during periods of growth or physical activity.
Vitamin Supplementation in PKU Medical
Well-formulated phenylalanine-free amino acid formula typically provides all required vitamins and minerals. When formula intake is insufficient, deficiencies can develop — particularly vitamin D, B12, selenium, iron, zinc, iodine, and folic acid. Annual laboratory screening of micronutrient status is recommended; targeted supplementation is initiated when deficiencies are identified.
W
WATCH Study Medical
A pivotal clinical registration study (PRISM-3) for pegvaliase (Palynziq®) in adults with PKU. Demonstrated significant blood Phe reductions and measurable improvements in quality of life under long-term therapy. Provided the evidence base for approval by the European Medicines Agency (EMA) in 2019.
X
Xylitol Medical
A sugar alcohol that occurs naturally in fruits and is commercially produced from birch wood. Contains no phenylalanine and can be used freely as a sweetener in PKU. Does not affect blood Phe levels. Frequently used in PKU-friendly baked goods, sweets, and low-protein speciality products as a sugar replacement.
Z
Zinc in PKU Medical
An essential trace element that can be low in PKU patients due to restricted intake of zinc-rich foods (meat, legumes, whole grains). Zinc is important for immune function, wound healing, protein synthesis, and taste perception. Included in phenylalanine-free amino acid formulas; annual blood monitoring is recommended when formula compliance is poor.

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