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.