Merck Serono, a division of Merck KGaA, Darmstadt, Germany, announced inclusion of the first patient in the validation study for the first quality-of-life questionnaire specific to phenylketonuria (PKU-QOL questionnaire). The validation study is the last development phase of this questionnaire designed to allow the medical community to quantify the impact of the disease and its treatment on PKU patients’ and parents’ quality of life.
“We are pleased to be supporting innovative real world research that will further explore the impact of this rare metabolic disorder on quality of life”, said Dr Annalisa Jenkins, Head of Global Drug Development and Medical at Merck Serono. “We believe that this questionnaire will further contribute to the understanding of the disease and how treatment options might potentially translate into measurable patient centric benefits.”
“Until now, the degree to which phenylketonuria impacts quality-of-life has not been explored in a reliable manner,” said Dr Annet Bosch, coordinating investigator of the validation study and a member of the project’s advisory board. “This specific quality-of-life questionnaire will be a useful tool for the medical community to improve patients’ treatment and follow-up and to increase our knowledge of the impact of phenylketonuria on quality-of-life.”
The study is a multi-centre, prospective, observational study which will be conducted in more than 30 clinical sites in seven countries. About 550 patients will be recruited from three age groups of PKU patients as well as a group of parents/caregivers of PKU patients to validate the four age-specific versions of the PKU-QOL questionnaire.
The PKU-QOL questionnaires are expected to be available for the healthcare community in seven languages by the beginning of 2013.
Disorders of phenylalanine (Phe) metabolism can lead to abnormal elevations of blood Phe levels, also called hyperphenylalaninemia (HPA). Two inborn errors of metabolism, phenylketonuria (PKU) and tetrahydrobiopterin (BH4) deficiency, account for the majority of cases of HPA.
PKU, a genetic disorder in the developed world, is caused by a deficiency of the enzyme phenylalanine hydroxylase (PAH). PAH is required for the metabolism of phenylalanine (Phe), an essential amino acid found in all protein-containing foods. If the active enzyme is not present in sufficient quantities, Phe accumulates to abnormally high levels in the blood and brain, resulting in a variety of complications including severe mental retardation and brain damage, mental illness, seizures and tremors, and cognitive problems. As a result of global newborn screening efforts implemented in the 1960s and early 1970s, virtually all PKU patients in developed countries are diagnosed at birth.
BH4 deficiency is a very rare inborn error of metabolism, and is estimated to account for 1–2 % of cases of HPA. BH4 deficiency is an autosomal recessive genetic condition and can result from deficiencies of any of the five different enzymes involved in BH4 synthesis and regeneration. BH4 is a necessary co-factor for PAH. Therefore, BH4 deficiency impairs PAH activity leading to a biochemical situation similar to PKU, with HPA resulting from deficient conversion of Phe to tyrosine. In addition, since BH4 is also a necessary co-factor for both tyrosine hydroxylase and tryptophan hydroxylase, BH4 deficiency causes deficiencies in the downstream neurotransmitter products of these amino acids including catecholamines and serotonin. Dietary limitation of whole protein or Phe intake is often not necessary with BH4 treatment. However, since BH4 does not cross the blood brain barrier, concomitant therapy with neurotransmitter precursors, i. e. levodopa and 5-hydroxytryptophan, may be necessary to boost central nervous system substrate levels for catecholamine and serotonin synthesis, respectively.
Merck Serono is the biopharmaceutical division of Merck KGaA, Darmstadt, Germany, discovers, develops, manufactures and markets prescription medicines of both chemical and biological origin in specialist indications.