International best practice for the evaluation of responsiveness to sapropterin dihydrochloride in patients with phenylketonuria

• Autores: Muntau, Ania Carolina; Adams, Darius J.; Bélanger Quintana, Amaya; Bushueva, Tatiana V.; Cerone, Roberto; Chien, Yin Hsiu; Chiesa, Ana Elena; Coşkun, Turgay; de las Heras, Javier; Feillet, François; Katz, Rachel; Lagler, Florian; Piazzon, Flavia; Rohr, Fran; van Spronsen, Francjan J.; Vargas, Paula; Wilcox, Gisela; Bhattacharya, Kaustuv
• Año de publicación: 2019
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: PHENYLALANINE; PHENYLKETONURIA; PREGNANCY; RESPONSE; SAPROPTERIN DIHYDROCHLORIDE; TETRAHYDROBIOPTERIN
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

Phenylketonuria (PKU) is an inherited metabolic disease caused by phenylalanine hydroxylase (PAH) deficiency. As the resulting high blood phenylalanine (Phe) concentration can have detrimental effects on brain development and function, international guidelines recommend lifelong control of blood Phe concentration with dietary and/or medical therapy. Sapropterin dihydrochloride is a synthetic preparation of tetrahydrobiopterin (6R-BH4), the naturally occurring cofactor of PAH. It acts as a pharmacological chaperone, reducing blood Phe concentration and increasing dietary Phe tolerance in BH4-responsive patients with PAH deficiency. Protocols to establish responsiveness to sapropterin dihydrochloride vary widely. Two meetings were held with an international panel of clinical experts in PKU management to develop recommendations for sapropterin dihydrochloride response testing. At the first meeting, regional differences and similarities in testing practices were discussed based on guidelines, a literature review, outcomes of a global physician survey, and case reports. Statements developed based on the discussions were sent to all participants for consensus (>70% of participants) evaluation using a 7-level rating system, and further discussed during the second meeting. The experts recommend sapropterin dihydrochloride response testing in patients with untreated blood Phe concentrations of 360–2000 μmol/L, except in those with two null mutations. For neonates, a 24-h sapropterin dihydrochloride loading test is recommended; responsiveness is defined as a decrease in blood Phe ≥30%. For older infants, children, adolescents, and adults, a test duration of ≥48 h or a 4-week trial is recommended. The main endpoint for a 48-h to 7-day trial is a decrease in blood Phe, while improved Phe tolerance is the endpoint to be assessed during a longer trial. Longer trials may not be feasible in some locations due to lack of reimbursement for hospitalization, while a 4-week trial may not be possible due to limited access to sapropterin dihydrochloride or public health regulation. A 48-h response test should be considered in pregnant patients who cannot achieve blood Phe ≤360 μmol/L with a Phe-restricted diet. Durability of response and clinical benefits of sapropterin dihydrochloride should be assessed over the long term. Harmonization of protocols is expected to improve identification of responders and comparability of test results worldwide.
Fil: Muntau, Ania Carolina. University Medical Center Hamburg Eppendorf; Alemania
Fil: Adams, Darius J.. Morristown Medical Center; Estados Unidos
Fil: Bélanger Quintana, Amaya. Hospital Ramón y Cajal; España
Fil: Bushueva, Tatiana V.. National Medical Research Center of Children's Health of the Ministry of Health of the Russian Federation; Rusia
Fil: Cerone, Roberto. Università degli Studi di Genova; Italia
Fil: Chien, Yin Hsiu. National Taiwan University Hospital; China
Fil: Chiesa, Ana Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
Fil: Coşkun, Turgay. Hacettepe University; Turquía
Fil: de las Heras, Javier. Universidad del País Vasco; España
Fil: Feillet, François. Children's University Hospital; Francia
Fil: Katz, Rachel. Ann and Robert Lurie Children's Hospital of Chicago; Estados Unidos
Fil: Lagler, Florian. Paracelsus Medical University; Austria
Fil: Piazzon, Flavia. Associação de Pais E Amigos Dos Excepcionais de São Paulo; Brasil
Fil: Rohr, Fran. Boston Children's Hospital; Estados Unidos
Fil: van Spronsen, Francjan J.. University of Groningen; Países Bajos
Fil: Vargas, Paula. Hospital Materno Infantil Presidente Vargas; Brasil
Fil: Wilcox, Gisela. University of Manchester; Reino Unido
Fil: Bhattacharya, Kaustuv. University of Sydney; Australia