Phenylketonuria screening and management in southeastern Europe - survey results from 11 countries.

BACKGROUND: We aimed to assess the current state of PKU screening and management in the region of southeastern Europe. METHODS: A survey was performed involving all identified professionals responsible for the PKU management in the 11 countries from South-Eastern region of Europe (Albania, Bulgaria, Bosnia and Herzegovina, Croatia, Kosovo, Macedonia, Moldova, Montenegro, Romania, Serbia, Slovenia). The questionnaire was designed to assess the characteristics regarding PKU management in three main areas: nation-wide characteristics, PKU screening, and characteristics of the PKU management in the responding centre. It consisted of 56 questions. The distribution and collection of the questionnaires (via e-mail) was taking place from December 2013 to March 2014. RESULTS: Responses from participants from 11 countries were included; the countries cumulative population is approx. 52.5 mio. PKU screening was not yet introduced in 4 of 11 countries. Reported PKU incidences ranged from 1/7325 to 1/39338 (and were not known for 5 countries). National PKU guidelines existed in 5 of 11 countries and 7 of 11 countries had PKU registry (registries included 40 to 194 patients). The number of PKU centers in each country varied from 1 to 6. Routine genetic diagnostics was reported in 4 of 11 countries. Most commonly used laboratory method to assess phenylalanine levels was fluorometric. Tetrahydrobiopterine was used in only 2 of 11 countries. Most frequently, pediatricians were caring for the patients. Dietitian was a member of PKU team in only 4 of 11 countries, while regular psychological assessments were performed in 6 of 11 countries. Patient's PKU society existed in 7 of 11 countries. CONCLUSIONS: The region of southeastern Europe was facing certain important challenges of PKU screening and management. Neonatal PKU screening should be introduced throughout the region. Furthermore, PKU management was falling behind internationally established standards-of-care in many aspects.

Newborn screening in southeastern Europe.

The aim of our study was to assess the current state of newborn screening (NBS) in the region of southeastern Europe, as an example of a developing region, focusing also on future plans. Responses were obtained from 11 countries. Phenylketonuria screening was not introduced in four of 11 countries, while congenital hypothyroidism screening was not introduced in three of them; extended NBS programs were non-existent. The primary challenges were identified. Implementation of NBS to developing countries worldwide should be considered as a priority.

Neurological symptoms, genotype-phenotype correlations and ethnic-specific differences in Bulgarian patients with Wilson disease.

OBJECTIVES: The aim of our study was to characterize the neurological symptoms in Bulgarian patients with Wilson disease (WD), to investigate genotype-phenotype correlations, and to test whether there are differences in phenotype between patients of different ethnic origin. PATIENTS AND METHODS: A total of 126 Bulgarian patients with WD were included in the study. Detailed history, physical and neurological examination, laboratory investigation of copper metabolism, slit-lamp examination, abdominal ultrasound, magnetic resonance imaging/computed tomography of the brain, molecular genetic testing, and statistical analysis were performed. RESULTS: Eighty-two patients demonstrated neurological signs. Tremor and dysarthria were most frequently observed. Rigidity, bradykinesia, and pyramidal signs were found in >25% of the patients. Dystonia, chorea, athetosis, ballismus, and epilepsy were rarely observed. We identified a total of 27 mutations of ATP7B. The most frequent mutation is p.H1069Q found on at least 1 allele in 78% of the patients. We did not find a significant correlation between p.H1069Q homozygosity and age of onset, ceruloplasmin level, and urinary copper excretion. The patients homozygous for p.H1069Q presented more frequently with hepatic signs. Mutations predicted to cause production of truncated protein are associated with earlier age at onset and lower ceruloplasmin level. In contrast to Bulgarian patients, Roma patients had an earlier disease onset and more frequent hepatic manifestation. CONCLUSIONS: WD presents with a variety of neurological signs. The mutation p.H1069Q is not uniformly associated with late onset and neurological presentation. Frameshift and nonsense mutations lead to severe phenotype. There are ethnic-specific differences in disease manifestation.