Search

Non treated phenylketonuria (PKU) has serious consequences such as growth retardation and intellectual impairment along with symptoms like erythematous eczema, fair skin and hair, seizures, autistic conduct and aggressive behavior. Pre-symptomatic biochemical diagnosis consists of identifying patients by blood phenylalanine (Phe) quantification through newborn screening. The confirmation is based on determining serum Phe and tyrosine levels. There is a wide spectrum of hyperphenylalaninemia clinical presentation, which ranges from mild forms which do not require nutritional treatment to the most severe form of the disease known as classic PKU. The aim of treatment is to avoid irreversible neurological impairment by stabilizing blood Phe level and keeping it within therapeutic concentration range. Once PKU diagnosis has been established, there are several criteria to decide when it is necessary to initiate treatment, we start it if Phe level is > 360 micromol/L (6 mg/L). Besides periodical Phe and Tyr testing, biochemical follow-up includes the measurement of necessary elements that guarantee normal physical and intellectual development such as selenium, zinc, B12 vitamin, folates, iron and long chain fatty acids. Clinical context is as important as biochemical status so periodic evaluation of nutritional, medical, social and psychological aspects should be included.

Hyperphenylalaninemia is caused by deficient enzyme activity of phenylalanine hydroxylase. It was one of the first genetic disorders susceptible to treatment with a natural protein restricted diet for life. While this treatment has proven effective in preventing mental retardation, eliminating certain foods from the diet entails the risk of nutritional deficiencies. For these reasons, new non-nutritional therapeutic strategies have been developed. One is the administration of sapropterin dihydrochloride, the synthetic form of tetrahydrobiopterin (BH4), which is the natural cofactor of phenylalanine hydroxylase, whose purpose is to reduce blood phenylalanine levels. We studied 6 patients with confirmed diagnosis of hyperphenylalaninemia or phenylketonuria. Sapropterin dihydrochloride was administered for 28 days and the intake of phenylalanine was calculated in each patient. To evaluate the response to sapropterin phenylalanine blood levels were measured at zero, eight and 24 hours and on days seven, 14, 21 and 28. The 24-hours recall was used to establish the intake of phenylalanine before and during the study. A positive response was determined as a reduction of phenylalanine blood levels ≥30% Four of the six patients responded positively to sapropterin dihydrochloride. The aim of this paper is to present the experience with sapropterin dihydrochloride in a group of Mexican patients with hyperphenylalaninemia.

Latin America is a region conformed by 20 countries characterized by a wide diversity among them, which can be demonstrated through several indicators such as rural population percentage, ethnicity, public health budget allocated and infant mortality rate; all these factors influence the extent of activities related to newborn screening. Phenylketonuria newborn screening programs vary among different Latin American countries; each one has its own history; quality standards, newborn population covered and the mandatory legislation of newborn screening. Epidemiological knowledge on phenylketonuria of this region is imprecise due to the lack of national statistic registries, thus avoiding an objective assessment of population coverage and disease incidence; therefore available data is obtained from isolated observations. Analysis of phenylketonuria and hyperphenylalaninemia based on available information of several Latin American newborn screening programs shows mean incidence values of 1: 23,518 and 1: 20,759 respectively; however, individual analysis of incidence by country indicates that phenylketonuria ranges between 1:12,473 and 1:161,748 live newborns.

Tetrahydrobiopterin (BH4) is an enzyme cofactor of phenylalanine hydroxylase, tyrosine hydroxylase and tryptophan hydroxylase. Three different enzymes affect BH4 synthesis: guanosine triphosphate cyclohydrolase I (GTP CH 1), 6-piruvoil tetrahydropterin synthase (PTPS), sepiapterin reductase (SR) and dihydropteridine reductase (DHPR) affects regeneration. BH4 deficiency causes defects in monoaminergic neurotransmitters synthesis and can be or not associated with hyperphenylalaninemia (HPA). Symptoms often begin in the first months of life with mental retardation, dystonic movements and posture, temperature control disorders, seizures, abnormal posture and tone, salivation and swallowing difficulties. Diagnosis is based on the following tests: pterins in urine, neurotransmitters and pterins in cerebrospinal fluid, reduced enzyme activity (in blood or fibroblasts) and mutational analysis. Treatment should be directed to normalize blood Phe levels and brain neurotransmitters with the administration of BH4 10 mg / kg / d, L-DOPA 10 mg/kg/day and 5-OH-tryptophan, 5 to 6 mg/kg/day. LDOPA should be given with carbidopa in order to inhibit the destruction of the L-dopa by the carboxylase. We describe 3 patients with BH4 deficiency treated at the Ramon y Cajal Hospital. All of them had a good neurological outcome with almost normal mental development.

Argentinean hyperphenylalaninemia newborn screening program was initiated by the Infantile Endocrinology Foundation in 1985. At the present it coexists with other several public health programs. To date phenylketonuria (PKU) incidence is 1:12,000 living newborns out of 1,300,000 subjects tested. Nutritional treatment consists of a diet restricted in phenylanine (Phe) and free of animal food, it is started in all children whose serum Phe levels are above 6 mg/dL, low tyrosine (Tyr) concentration, and a Phe to Tyr ratio >3, although patients between 2 to 6 mg/dL are closely followed. Periodic blood Phe quantification and dietetic instructions to the patient are required in order to keep Phe levels in a safe range that preserves nervous system maturing, and prevention of mental retardation which is inherent to non-treated disease. Educational activities constitute the core of the teamwork; they are destined to achieve the best psycho-social integration of the patient to society. Patients’ mothers are trained to follow dietetic quantities of Phe following the “Practical guidance for phenylketonuric patients’ nutrition”. Diet compliance is a complex process which should be evaluated in individual and familiar context in order to identify the need for extra medical support; adolescents are the most vulnerable age population. It has been noted that late diagnosed patients who were given the adequate proposed treatment improved in terms of neurological symptoms, behavioral issues as well as in their potential for rehabilitation.

La fenilcetonuria pertenece al grupo de las hiperfenilalaninemias. Es una enfermedad infantil, metabólica, causada por un déficit de la enzima (sustancia proteica capaz de activar indirectamente una reacción química definida) del hígado llamada fenilalanín-hidroxilasa (1). La alteración en el metabolismo del aminoácido llamado fenilalanina, sobre el que actúa la enzima deficiente, provoca un acúmulo excesivo de fenilalanina en los líquidos del organismo (1). La fenilcetonuria es una enfermedad progresiva severa que puede producir retraso mental si no se trata con una dieta libre de alimentos que contengan este aminoácido a tiempo (3-5)