The challenges of managing coexistent disorders with phenylketonuria: 30 cases.
BACKGROUND
The few published case reports of co-existent disease with phenylketonuria (PKU) are mainly genetic and familial conditions from consanguineous marriages. The clinical and demographic features of 30 subjects with PKU and co-existent conditions were described in this multi-centre, retrospective cohort study.


METHODS
Diagnostic age of PKU and co-existent condition, treatment regimen, and impact of co-existent condition on blood phenylalanine (Phe) control and PKU management were reported.


RESULTS
30 patients (11 males and 19 females), with PKU and a co-existent condition, current median age of 14 years (range 0.4 to 40 years) from 13 treatment centres from Europe and Turkey were described. There were 21 co-existent conditions with PKU; 9 were autoimmune; 6 gastrointestinal, 3 chromosomal abnormalities, and 3 inherited conditions. There were only 5 cases of parental consanguinity. Some patients required conflicting diet therapy (n=5), nutritional support (n=7) and 5 children had feeding problems. There was delayed diagnosis of co-existent conditions (n=3); delayed treatment of PKU (n=1) and amenorrhea associated with Grave's disease that masked a PKU pregnancy for 12 weeks. Co-existent conditions adversely affected blood Phe control in 47% (n=14) of patients. Some co-existent conditions increased the complexity of disease management and increased management burden for patients and caregivers.


CONCLUSIONS
Occurrence of co-existent disease is not uncommon in patients with PKU and so investigation for co-existent disorders when the clinical history is not completely consistent with PKU is essential. Integrating care of a second condition with PKU management is challenging.
The Children's Hospital, Birmingham, UK.
A
A
MacDonald
Center for PKU, The Kennedy Centre, University Hospital, Glostrup, Copenhagen, Denmark.
K
K
Ahring
Centro de Genética Médica Doutor Jacinto de Magalhães, CHP EPE, Porto, Portugal; Unit for Multidisciplinary Research in Biomedicine, Abel Salazar Institute of Biomedical Sciences, University of Porto-UMIB/ICBAS/UP, Porto, Portugal.
M F
MF
Almeida
Hospital Ramon y Cajal Madrid, Spain.
A
A
Belanger-Quintana
Dietmar-Hopp Metabolic Center, University Children's Hospital, Heidelberg, Germany.
N
N
Blau
Division of Inherited Metabolic Diseases, University Hospital, Padua, Italy.
A
A
Burlina
Hospital for Sick Children, Great Ormond Street, London, UK.
M
M
Cleary
Department of Inherited Metabolic Disorders, Hacettepe University, Ankara, Turkey.
T
T
Coskum
Department of Metabolism and Nutrition, Dr. von Hauner Children's Hospital, University of Munich, Munich, Germany.
K
K
Dokoupil
The Children's Hospital, Birmingham, UK.
S
S
Evans
Hôpital d'enfants Brabois, Vandoeuvre les Nancy, France.
F
F
Feillet
Department of Pediatrics, Endocrinology, Diabetology, Metabolic Diseases and Cardiology, Pomeranian Medical University, Szczecin, Poland.
M
M
Giżewska
Department of Nutrition and Dietetics, Hacettepe University, Ankara, Turkey.
H
H
Gokmen Ozel
Dr. von Hauner Children's Hospital, University of Munich, Munich, Germany.
A S
AS
Lotz-Havla
Department of Paediatrics and Haematology, Pomeranian Medical University, Szczecin, Poland.
E
E
Kamieńska
CHRU de Tours, service de medicine interne, Université François Rabelais, Tours, France.
F
F
Maillot
Depart Ped, San Paolo Hosp Univ Milan, Milan, Italy.
A M
AM
Lammardo
University Children's Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany.
A C
AC
Muntau
Dr. von Hauner Children's Hospital, University of Munich, Munich, Germany.
A
A
Puchwein-Schwepcke
Hôpital Universitaire des Enfants Reine Fabiola, Brussels, Belgium.
M
M
Robert
Centro de Genética Médica Doutor Jacinto de Magalhães, CHP EPE, Porto, Portugal; Faculdade de Ciências da Saúde, Universidade Fernando Pessoa, Porto, Portugal; Center for Health Technology and Services Research (CINTESIS), Portugal.
J C
JC
Rocha
The Children's Hospital, Birmingham, UK.
S
S
Santra
Hospital for Sick Children, Great Ormond Street, London, UK.
R
R
Skeath
Department of Pediatrics, Endocrinology, Diabetology, Metabolic Diseases and Cardiology, Pomeranian Medical University, Szczecin, Poland.
K
K
Strączek
Division of Inborn Metabolic Diseases, University Children's Hospital, Heidelberg, Germany.
F K
FK
Trefz
Section of Metabolic Diseases, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
E
E
van Dam
Section of Metabolic Diseases, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
M
M
van Rijn
Section of Metabolic Diseases, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
F
F
van Spronsen
The Children's Hospital, Birmingham, UK.
S
S
Vijay
D000293:Adolescent; D000328:Adult; D001327:Autoimmune Diseases / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000628:therapy*; D001708:Biopterins / Q000031:analogs & derivatives / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D003241:Consanguinity; D004032:Diet; D019468:Disease Management; D005060:Europe; D005260:Female; D005767:Gastrointestinal Diseases / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000628:therapy*; D006801:Humans; D007223:Infant; D008297:Male; D010649:Phenylalanine / Q000097:blood*; D010661:Phenylketonurias / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000628:therapy*; D011247:Pregnancy; D012189:Retrospective Studies; D014421:Turkey
D001708:Biopterins; D010649:Phenylalanine; C003402:sapropterin
Co-existent; Diet; Phenylalanine; Phenylketonuria; Sapropterin