BACKGROUNDA novel therapeutic strategy for phenylketonuria (PKU) has been initiated in Japan. Hyperphenylalaninemia (HPA) results from a phenylalanine hydroxylase (PAH) enzyme deficiency or a deficiency of its cofactor, tetrahydrobiopterin (BH4). BH4 can normalize blood phenylalanine levels in BH4 deficiency, but typically not in PKU. However, since 1999 it has been reported that many HPA patients (serum phenylalanine <20 mg/dL) showed a gradual decrease of serum phenylalanine levels after 24 hours from BH4 loading. The BH4 responsiveness seems to be regulated in mild PKU by PAH mutations, and affected by the BH4 dose and administration period.

METHODS AND RESULTSIn 2002 we formulated a provisional diagnostic criteria for patients with BH4-responsive PAH deficiency, and newly diagnosed 19 patients in 100 HPA cases between 2002 and 2006. The incidence in the recent 5 years for BH4-responsive mild PKU among patients with PAH deficiency was 25 %.

CONCLUSIONA total of 31 patients was detected in the past 10 years, and the incidence detected using the provisional diagnostic criteria had increased to 25% among PAH deficient patients. BH4 treatment for BH4-responsive mild PKU is a new and effective pharmacotherapy, which replaces or liberalises the phenylalanine-restricted diets for a considerable number of mild PKU patients.

Biopterin ; analogs & derivatives ; therapeutic use ; Humans ; Infant, Newborn ; Japan ; Phenylketonurias ; diagnosis ; drug therapy ; Severity of Illness Index ; Time Factors

Purpose: To clarify staff awareness and the current status of facilities regarding end-of-life care and the planning for severely disabled children and adults. Methods: A questionnaire survey on ACP was conducted on all 466 staff members of a residential facility for children with medical disabilities. Results: The response rate was 77.0%; 20.2% of direct support staff and 50.9% of indirect support staff answered that they had never heard of ACP (or life conferences). The respondents had experienced discussions with the patient and family members about medical treatment and care in the last stage of life was 27.1%. The content of the discussions was more often about the family's values and wishes than about the patient's values and intentions, and the timing of the start of the discussions was often when death was approaching .More than 70% of the direct supporters wished to participate in ACP, discussions, and they wished to receive training in advance of ACP implementation .The majority of staff agreed that surrogate decision-making in the absence of family members should be discussed by a multidisciplinary medical and care team, and that the results should be approved by an ethics committee. Conclusion: Training for staff is necessary for the promotion of ACP in medical-type residential care facilities for children with disabilities.