An exceptional Albanian family with seven children presenting with dysmorphic features and mental retardation: maternal phenylketonuria

BMC Pediatrics

Wolfgang Rascher²  Jörg Dötsch²  Corina Weigel²  Hans G Topf²  Stefan Schellmoser³  Johannes Zschocke¹  Ina Knerr² 

[1] Institute of Human Genetics, University of Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany;Children and Youth Hospital, University of Erlangen-Nuremberg, Loschge Street 15, 91054 Erlangen, Germany;Paediatric Practice, Demut Street 21, 9000 St. Gallen, Switzerland

关键词: pregnancy outcome;    phenylketonuria;    phenylalanine;    Maternal phenylketonuria;   

Others  :  1181694
DOI  :  10.1186/1471-2431-5-5

 received in 2004-11-29, accepted in 2005-04-05,  发布年份 2005

【 摘 要 】

Background

Phenylketonuria is an inborn error of amino acid metabolism which can cause severe damage to the patient or, in the case of maternal phenylketonuria, to the foetus. The maternal phenylketonuria syndrome is caused by high blood phenylalanine concentrations during pregnancy and presents with serious foetal anomalies, especially congenital heart disease, microcephaly and mental retardation.

Case presentation

We report on an affected Albanian woman and her seven children. The mother is affected by phenylketonuria and is a compound heterozygote for two pathogenetic mutations, L48S and P281L. The diagnosis was only made in the context of her children, all of whom have at least one severe organic malformation. The first child, 17 years old, has a double-chambered right ventricle, vertebral malformations and epilepsy. She is also mentally retarded, microcephalic, exhibits facial dysmorphies and small stature. The second child, a girl 15 years of age, has severe mental retardation with microcephaly, small stature and various dysmorphic features. The next sibling, a boy, died of tetralogy of Fallot at the age of three months. He also had multiple vertebral and rib malformations. The subsequent girl, now eleven years old, has mental retardation, microcephaly and epilepsy along with facial dysmorphy, partial deafness and short stature. The eight-year-old child is slightly mentally retarded and microcephalic. A five-year-old boy was a premature, dystrophic baby and exhibits mental retardation, dysmorphic facial features, brachydactyly and clinodactyly of the fifth finger on both hands. Following a miscarriage, our index case, the youngest child at two years of age, is microcephalic and mentally retarded and shows minor facial anomalies. All children exhibit features of phenylalanine embryopathy caused by maternal phenylketonuria because the mother had not been diagnosed earlier and, therefore, never received any diet.

Conclusion

This is the largest family suffering from maternal phenylketonuria reported in the literature. Maternal phenylketonuria remains a challenge, especially in woman from countries without a neonatal screening program. Therefore, it is mandatory to be alert for the possibility of maternal phenylketonuria syndrome in case of a child with the clinical features described here to prevent foetal damage in subsequent siblings.

【 授权许可】

   
2005 Knerr et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 5.

Figure 2.

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