Phenylketonuria symptoms

Infants with classic phenylketonuria (PKU) are normal at birth but if untreated show slow development, severe mental retardation, autistic symptoms, and loss of motor control. Children may have pale skin and white-blonde hair. The neurotoxic effects relate to high levels of phenylalanine and not to the phenylketones from which the name of the disease derives. Infants are routinely screened a few days after birth for blood phenylalanine level. Treatment consists of a life-long semisynthetic diet restricted in phenylalanine (smalt quantities are necessary because it is an essential amino acid). Aspartame (N-aspartyl-phenylalanine methyl ester), which is widely used as an artificial sweetener, must be strictly avoided by phenyiketonurics. 

As discussed above, in the case of phenylketonuria, early intervention can make the difference between mental retardation and a near normal life course for a newborn. Congenital adrenal hyperplasia and maple syrup urine disease are two examples of neonatal hereditary disorders where early diagnosis and medical intervention can make the difference between life and death for the newborn. In addition, in a number of genetic diseases, early diagnosis and treatment can help ameliorate symptoms these include fragile X syndrome, homocystinuria, sickle cell anemia, cystic fibrosis, and many /1-thalassemias. 

Phenylalanine Phenylketonuria and Vomiting is an early neonatal symptom, Phenylalanine-... 

Extrapyramidal symptoms developed with co-trimox-azole in a girl with dihydropteridine reductase deficiency and rapidly disappeared after withdrawal. This variant of phenylketonuria should be considered in all infants found to have raised phenylalanine concentrations during the neonatal period (46). 

The metabolic defect involved in alkaptonuria w as suggested by Bateson (34) as early as 1902 to be inherited as a recessive Mendelian character, and later evidence has supported this prediction (395, 643). Gross (322) in 1914 concluded that it was due to lack of a specific enzyme. Alkaptonuria, unlike phenylketonuria, is not accompanied by mental symptoms and is not an incapacitating disorder except insofar as it may lead to ochronosis and arthritis (c/. 598). 

A 1-year-old girl presents at your clinic the day after you saw the 3-month-old boy. The symptoms are the same so you order a test on phenylalanine hydroxylase to confirm your diagnosis of phenylketonuria. To your surprise the phenylalanine hydroxylase activity is well within the normal range. Which of the following might you check next to support your diagnosis ... 

Brumm VL, Bilder D, Waisbren SE. Psychiatric symptoms and disorders in phenylketonuria. Mol Genet Metab. 2010 99 Suppl l S59-63. 

Burton B, et al. A randomized, placebo-controUed, double-bhnd study of sapropterin to treat ADHD symptoms and executive function impairment in children and adults with sapropterin-responsive phenylketonuria Mol Genet Metab. 2014. http //dx.doi.org/10.1016/ j.ymgme.2014.11.011. 

The presence of indol derivatives in the urine of phenylketonuric patients is more difficult to understand. The experiments of Tyler and Armstrong [79] suggest that there are side effects of the main metabolic block. By keeping the patient on a diet containing only sufficient amounts of phenylalanine to maintain normal growth and normal protein synthesis, these authors demonstrated that all these patients biochemical symptoms disappeared, including the excretion of indole derivatives. Furthermore, it was demonstrated that hydroxytryptophan decarboxylase (an enzyme identical to dopa decarboxylase) is inhibited by the abnormal metabolites in a way analogous to that for dopa decarboxylase. This may explain both the low levels of phenyltryptamine in patients with phenylketonuria and the accumulation of unidentified indole compounds [80, 81]. 

No matter what the type of brain damage produced by an inborn error like phenylketonuria or by hypoxia, it is not reversible and frequently very similar in its symptoms does this mean that the lesions (i.e. biochemical alteration) produced are also very similar or even unique ... 

Several inborn errors of metabolism are concerned with the metabolism of L-phenylalanine and L-tyrosine in mammals. In several cases it has been possible to demonstrate that such biochemical disorders are associated with the absence or partial deficiency of a particular enzymatic activity. Phenylketonuria results from the absence of a normal L-phenylalanine hydroxylase activity and individuals suffering from this disease are unable to convert L-phenylalanine to L-tyrosine. Under these conditions the metabolism of the amino acid to phenylpyruvic acid, phenyl-lactic acid and phenyl acetyl glutamine is greatly exaggerated. Phenylketonuria is a severe disorder and results in a marked mental retardation, particularly in children. It is generally assumed that it is the accumulation of abnormal metabolites which is responsible for the mental symptoms associated with the disease. 

Beyond the genetic factors, the causes of ADHD are unknown, and very few studies have examined the relationship between ADHD and exposures to environmental chemicals. It is known, however, that maternal prenatal exposures to lead, alcohol, tobacco smoke, and marijuana are known to result in the birth of children with high incidences of ADHD [14-17]. It has also been established that exposure to excessive quantities of phenylalanine either prenatally in utero, as a result of the mother having phenylketonuria (PKU) and fetus not having PKU, or postnatally where the child has PKU, results in the development of ADHD hyperactive and behavioral symptoms [18,19]. The mechanisms for these effects remain unknown, but these reactions to specific agents further demonstrate that environmental exposures may be triggers for ADHD. It is also known that many different chemicals trigger developmental... 

The patient with the classical form of the disease (Dancis and Levitz, 1978) appears normal at birth, but shows symptoms by the end of the first week, with poor feeding, vomiting and lethargy. Muscular hypertonicity and convulsions may appear. Death usually occurs as a result of intercurrent infections within the first year of life, and children surviving into their first and second years suffer severe brain damage. Abnormal amino acidaemia and amino aciduria with abnormal keto aciduria are apparent within the first week of life. Treatment by dietary protein restriction and the use of artificial amino acid mixtures has been attempted but is much more difficult and less successful in practise than treatment of phenylketonuria (Chapter 16), since most foods have a high content of branched-chain amino acids (Dancis and Levitz, 1978). Careful laboratory supervision is essential, there is a continued risk of recurrent infections, and it is unclear how long therapy will be required. 

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