Inborn errors in amino acid metabolism

 

Phenylketonuria (PKU)

Phenylketonuria is caused by deficiency of phenylalanine hydroxylase, the most common clinically encountered inborn error of amino acid metabolism. Characterized by accumulation of phenylalanine (and deficiency of tyrosine). In PKU, phenylalanine is present in elevated concentrations in tissues, plasma and urine. Phenyl lactate, phenyl acetate and phenyl pyruvate, which are not normally produced in significant amounts in the presence of functional phenylalanine hydroxylase are also elevated in PKU. These metabolites give urine a characteristic musty (mousy) odor.

CNS symptoms

Mental retardation, failure to walk or talk, seizures, hyperactivity, tremor, microcephaly and failure to grow are characteristic findings in PKU. The patient with untreated PKU typically shows symptoms of mental retardation by the age of 1 year.

Hypopigmentation

Deficiency of pigmentation (fair hair, light skin color and blue eyes). The hydroxylation of tyrosine by tyrosinase, which is the first step in the formation of the pigment melanin, is competitively inhibited by the high levels of phenylalanine present in PKU.

Early diagnosis of phenylketonuria is important because the disease is treatable by dietary means. Infants with PKU can’t be fed breast milk and must consume a special formula that’s often known as Lofenalac (a formulae with no phenylalanine). Avoid foods high in protein (eggs, cheese, nuts, milk).

 

Albinism

It refers to a group of conditions in which a defect in tyrosine metabolism results in a deficiency in the production of melanin (deficiency of tyrosinase). These defects result in the partial or full absence of pigment from the skin, hair and eyes. Albinism affects individuals have vision defects and photophobia (sunlight hurts their eyes). They are at increased risk for skin cancer.

 

Marple syrup urine disease

Rare autosomal recessive disorder. It is caused by partial of complete deficiency in branched chain alpha keto acid dehydrogenase, an enzyme complex that decarboxylates leucine, isoleucine and valine. Their amino acids and their corresponding alpha keto acids accumulate in the blood, causing a toxic effect that interferes with brain functions. The disease is characterized by feeding problems, vomiting, dehydration, severe metabolic acidosis and a characteristic maple syrup odor and sweet taste to the urine. If untreated, the disease leads to mental retardation, physical disabilities and even death. This disease is treated with a synthetic formula that contains limited amounts of leucine, isoleucine and valine.

 

Alkaptonuria

A rare metabolic condition involving a deficiency in homogenic acid oxidase. The condition has three characteristics symptoms.

1.    Homogentisic aciduria (the patient’s urine contains elevated levels of homogentisic acid, which is oxidized to a dark pigment on standing).

2.    Large joint arthritis

3.    Black ochronotic pigmentation of cartilage and collagenous tissue.

Patients with alkaptonuria are usually asymptomatic until about age 40. Dark staining of the diapers sometimes can indicate the disease in infants. Diets low in protein – especially in phenylalanine and tyrosine .help reduce the levels of hormogentisic acid, and decrease the amount of pigment deposited in body tissues.