A 34-year-old woman, of Argentinean nationality, referred from Neuropaediatrics to the Metabolic Diseases Unit of the Hospital Ramón y Cajal, in order to rule out metabolic disease, because she had two children aged 12 and 9 years, from different fathers, with microcephaly and severe mental retardation. The patient reported having had another child who, due to cardiac malformation, died at 3 months of age. She was married, spoke normally and performed activities of daily living. She sometimes had problems with money exchange and had not been able to complete her studies but could read, write, add, subtract, multiply and divide (only by 1 digit). His IQ was estimated at 70-75, corresponding to mild-moderate mental retardation. He was not undergoing any treatment or reported any known illnesses and had no family history of interest.
In both children, Phe levels were normal, 70 and 92 micromol/L. However, Phe levels were determined in the patient and were 1,140 micromol/L (normal < 120 micromol/L). Phe levels at diagnosis, between 660 and 1,200 micromol/L, condition a classification of mild-moderate PKU phenotype. Differential diagnosis was made with disorders of pterin metabolism, which were found to be normal. The following mutational changes were found in the PAH gene: c.165delT (p.Phe55fs) / c.q62G > A (p.Val388Met), with both children being carriers of the p.Phe55fs mutation only.
After the diagnosis of phenylketonuria in the mother, an overload of Tetrahydrobiopterin (BH4) was performed to discover a possible response to this pharmacological treatment, since in some PKU patients it is possible to improve PAH activity by giving pharmacological doses of its cofactor, but in this patient the phenylalanine levels did not undergo significant changes and therefore she was considered a non-responder.

Treatment was started with a diet limited in phenylalanine in order to maintain phenylalanine levels below 660 micromol/L (maximum levels allowed in adults without pregnancy) and weekly control of phenylalanine in blood. To this end, we adjusted the diet to 20-25 g of high biological value proteins/day (PAVB: milk, eggs, meat, fish, cheese, cereals and pulses) divided into breakfast, lunch and dinner (5-10 and 10 g), with freedom in vegetables, natural fruit, peeled potatoes, olives, sugar, oils, butter, corn starch (Maizena®), spices and low-protein foods Loprofín®, Aglutella® and Aproten® purchased through the Association of PKU patients in Madrid.
To the PAVB were added 60 g of special proteins without phenylalanine (PrXPhe) distributed in 4 intakes/day, in the form of special preparations containing essential amino acids without phenylalanine with carbohydrates, essential fatty acids, ions, oligoelements and vitamins.
The weekly evolution of the Phe levels during the first 3 months of follow-up showed levels of 498 ± 15 micromoles/L. Subsequently the family returned to Argentina where they are currently undergoing treatment.