*8.1. Dietary Treatment*

PKU is the most common inborn error of metabolism; in it, the accumulation of L-Phe causes clinical features such as mental retardation, eczema, microcephaly, and behavioral problems. Blood Phe levels, which depend on the enzymatic deficiency, dictate the severity of the clinical phenotype [37]. It has been more than 65 years since the successful establishment of dietary restrictions to treat PKU, but that diet has to be maintained for life [109]. The PKU diet is low in Phe and is supplemented with a special medicinal formula to supply vitamins, amino acids (except Phe), and minerals. However, dietary restrictions are cumbersome economically and socially and can lead to nutritional deficiencies. Moreover, adhering to dietary restrictions is difficult for older patients, resulting in increased blood Phe levels. Large neutral amino acids (LNAAs) can be included in the diet to reduce the absorption of Phe in the brain by competing with the transporter across the blood–brain and gastrointestinal barriers. Because inadequate evidence supports the long-term outcomes of LNAA treatment, it is used only as a short-term therapy. Nevertheless, dietary treatment is the foundation of PKU managemen<sup>t</sup> upon which novel improved therapies are being developed [109,110].

Dietary restrictions are the most common treatment for both PKU and HT1 patients. Patients with HT1 are recommended to consume a low tyr/Phe diet and Nitisinone [111].
