Inherited Metabolic Disorders

Types of Inherited Metabolic Disorders continued...

Galactosemia: Impaired breakdown of the sugar galactose leads to jaundice, vomiting, and liver enlargement after breast or formula feeding by a newborn.

Maple syrup urine disease: Deficiency of an enzyme called BCKD causes buildup of amino acids in the body. Nerve damage results, and the urine smells like syrup.

Phenylketonuria (PKU): Deficiency of the enzyme PAH results in high levels of phenylalanine in the blood. Mental retardation results if the condition is not recognized.

Glycogen storage diseases: Problems with sugar storage lead to low blood sugar levels, muscle pain, and weakness.

Mitochondrial disorders: Problems inside mitochondria, the powerhouses of cells, lead to muscle damage.

Friedreich ataxia: Problems related to a protein called frataxin cause nerve damage and often heart problems. Inability to walk usually results by young adulthood.

Peroxisomal disorders: Similar to lysosomes, peroxisomes are tiny spaces filled with enzymes inside cells. Poor enzyme function inside peroxisomes can lead to buildup of toxic products of metabolism. Peroxisomal disorders include:

• Zellweger syndrome (abnormal facial features, enlarged liver, and nerve damage in infants)
• Adrenoleukodystrophy (symptoms of nerve damage can develop in childhood or early adulthood depending on the form.)

Metal metabolism disorders: Levels of trace metals in the blood are controlled by special proteins. Inherited metabolic disorders can result in protein malfunction and toxic accumulation of metal in the body:

• Wilson disease (toxic copper levels accumulate in the liver, brain, and other organs)
• Hemochromatosis (the intestines absorb excessive iron, which builds up in the liver, pancreas, joints, and heart, causing damage)

Organic acidemias:methylmalonic acidemia and propionic acidemia.

Urea cycle disorders:ornithine transcarbamylase deficiency and citrullinemia

Symptoms of Inherited Metabolic Disorders

The symptoms of genetic metabolic disorders vary widely depending on the metabolism problem present. Some symptoms of inherited metabolic disorders include:

• Lethargy
• Poor appetite
• Abdominal pain
• Vomiting
• Weight loss
• Jaundice
• Failure to gain weight or grow
• Developmental delay
• Seizures
• Coma
• Abnormal odor of urine, breath, sweat, or saliva

The symptoms may come on suddenly or progress slowly. Symptoms may be brought on by foods, medications, dehydration, minor illnesses, or other factors. Symptoms appear within a few weeks after birth in many conditions. Other inherited metabolic disorders may take years for symptoms to develop.

Diagnosis of Inherited Metabolic Disorders

Inherited metabolic disorders are present at birth, and some are detected by routine screening. All 50 states screen newborns for phenylketonuria (PKU). Most states also test newborns for galactosemia. However, no state tests babies for all known inherited metabolic disorders.

Improved testing technology is leading many states to expand newborn screening for genetic metabolic disorders. The National Newborn Screening and Genetics Resources Center provides information on each state's screening practices.

If an inherited metabolic disorder is not detected at birth, it is often not diagnosed until symptoms appear. Once symptoms develop, specific blood or DNA tests are available to diagnose most genetic metabolic disorders. Referral to a specialized center (usually at a university) increases the chances of a correct diagnosis.