Information on the following diseases can be found in the Related Disorders section of this report:

• Maple Syrup Urine Disease
• Methylmalonic Acidemias
• Multiple Carboxylase Deficiency
• Propionic Acidemia

Valinemia is usually present at birth. Symptoms in the newborn period include protein intolerance, metabolic acidosis, frequent vomiting, failure to thrive, and coma. The condition may become life-threatening. The levels of the amino acid valine in the blood and urine are elevated. Abnormally low muscle tone, excessive drowsiness, and/or hyperactivity can also occur.
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Valinemia is a recessive genetic disorder. Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.

All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.
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Valinemia is a rare disorder, occurring once in about 250,000 live births in the United States. It is present in affected infants at birth.
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Related disorders include maple syrup urine disease, propionic acidemia, methylmalonic acidemia, and multiple carboxylase deficiency.

Maple syrup urine disease (MSUD) is an extremely rare inherited metabolic disorder characterized by a distinctive sweet odor of the urine and sweat. It is a serious disorder that, unless treated promptly and correctly, can be life threatening. Therapy must be started at the earliest possible age to achieve the best results. MSUD is manageable, just as diabetes is manageable, but care and attention must be given to diet and to the treatment of even minor illnesses.

Symptoms develop because the body is unable to break down (metabolize) three of the essential amino acids, leucine, isoleucine, and valine. They are essential because they are used by the body to build proteins, and they are three of 11 amino acids that must be obtained as part of the daily diet since the body cannot synthesize them. These three amino aids share a common characteristic of chemical structure and are thus known as the branched chain amino acids (BCAAs). An affected newborn will present with abnormally high concentrations of acidic metabolic by-products of the BCAAs in the blood and other tissues (metabolic acidosis) that, if left untreated, may lead to seizures or coma, and may be life-threatening.

Propionic acidemia is a rare metabolic disorder characterized by deficiency of propionyl CoA carboxylase, an enzyme involved in the breakdown (catabolism) of the chemical "building blocks" (amino acids) of certain proteins. Symptoms most commonly become apparent during the first weeks of life and may include abnormally diminished muscle tone (hypotonia), poor feeding, vomiting, listlessness (lethargy), excessive loss of fluids from bodily tissues (dehydration), and episodes of uncontrolled electrical activity in the brain (seizures). Without appropriate treatment, coma and potentially life-threatening complications may result. In rare cases, the condition may become apparent later during infancy and may be associated with less severe symptoms and findings. Propionic acidemia is inherited as an autosomal recessive trait.

The methylmalonic acidemias are organic acidemias caused by an enzymatic defect in the metabolism of four amino acids (methionine, threonine, isoleucine and valine). This results in an abnormally high level of acid in the blood (academia) and body tissues. In the acute form, drowsiness, coma, and seizures may occur. Mental retardation is a long-term consequence. The disorder may be caused by a deficiency of one or more of the enzymes methylmalonyl CoA mutase, methylmalonyl racemase, or adenosylcobalamin synthetic enzymes. Excretion of methylmalonate, a product of amino acid metabolism, in the urine is abnormally high and therefore is a marker of the disorder. All known organic acidemias are inherited as autosomal recessive traits.

Multiple carboxylase deficiency is a genetic metabolic disorder that leads to impaired activity of three enzymes that are dependent on the vitamin biotin: propionyl CoA carboxylase, beta-methylcrotonyl CoA carboxylase, and pyruvate carboxylase. This condition results from a defect in cellular biotin transport or metabolism. Symptoms of the disorder include acidity of the blood and body tissues (acidosis), a widespread red skin rash, baldness, and slowed physical development. The disorder occurs in both a neonatal and a late-onset form and is treatable.
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Diagnosis
Diagnosis depends on the precise laboratory identification and measurement of metabolic products that accumulate in the blood and urine. Sophisticated chromatographic equipment is required to identify these metabolites.

Treatment
A diet low in valine introduced during early infancy usually improves symptoms of valinemia, and lowers the valine concentrations in the blood to normal levels.
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McKusick VA, Ed. ONLINE MENDELIAN INHERITANCE IN MAN (OMIM). The Johns Hopkins University. Entry Number; 277100: Last Edit Date; 8/22/1994.

TEXTBOOK
Thoene JG. Disorders of amino acid metabolism. In: Stein JH. Ed.-in-Chief. Internal Medicine. 4th Ed. Mosby, St.Louis. 1994:1462-72.

Scriver CR, Beaudet AL, Sly WS, et al. Eds. The Metabolic Molecular Basis of Inherited Disease. 7th ed. McGraw-Hill Companies. New York, NY; 1995:1388-92; 1410-15.

JOURNAL ARTICLES
Ogier de Baulny H, Saudubray JM. Branched –chain organic acidurias. Semin Neonat. 2002;7:65-74

Di Rocco M, Boncompagni A, Caruso U. Clinics for adults with hereditary metabolic diseases. Am J Med. 2002;112:160-61.

Chace DH, DiPerna JC, Kalas TA, et al. Rapid diagnosis of methylmalonic and propionic acidemias: quantitative tandem mass spectrometric analysis of propionylcarnitine in filter paper blood specimens obtained from newborns. Clin Chem;2001:47:2040-44.

Reddi OS, Reddy SV, Reddy KR. A sibship with hypervalinemia. Hum Genet. 1977;39:139-42.

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Valinemia
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