HEREDITARY METABOLIC HEREDITARY METABOLIC DISEASESDISEASES

Particular risk factors Particular risk factors are:are:

••Advanced maternal age (e.g. Advanced maternal age (e.g. Down's syndrome)Down's syndrome)

• • Family history of inherited Family history of inherited diseases (e.g. fragile X diseases (e.g. fragile X syndrome, Huntington's chorea)syndrome, Huntington's chorea)

• • Previous child with genetic Previous child with genetic disorder (e.g. Tay-Sachs diseasedisorder (e.g. Tay-Sachs disease

PHENYLKETONURIAPHENYLKETONURIA

Excess phenylalanine is normally Excess phenylalanine is normally converted to tyrosine, another converted to tyrosine, another amino acid, and eliminated from amino acid, and eliminated from the body. Without the enzyme that the body. Without the enzyme that converts it to tyrosine, converts it to tyrosine, phenylalanine builds up in the phenylalanine builds up in the blood and is toxic to the brain, blood and is toxic to the brain, causing mental retardation.causing mental retardation.

SYMPTOMSSYMPTOMS mental retardation over the first few mental retardation over the first few

yearsyears

of life, which eventually becomes of life, which eventually becomes severe. Other symptoms include severe. Other symptoms include seizures, nausea and vomiting, an seizures, nausea and vomiting, an eczema-like rash, lighter skin and hair eczema-like rash, lighter skin and hair than their family members, than their family members, aggressive or self-injurious behavior, aggressive or self-injurious behavior, hyperactivity, and sometimes hyperactivity, and sometimes psychiatric symptoms. psychiatric symptoms.

Untreated children often give Untreated children often give off a "mousy" body and urine off a "mousy" body and urine odor as a result of a by-odor as a result of a by-product of phenylalanine product of phenylalanine (phenylacetic acid) in their (phenylacetic acid) in their urine and sweat.urine and sweat.

MAPLE SYRUP URINE DISEASEMAPLE SYRUP URINE DISEASE

By-products of By-products of lecine, lecine, isoleucine and valineisoleucine and valine build up, build up, causing neurologic changes, causing neurologic changes, including seizures and mental including seizures and mental retardation. These by-products retardation. These by-products also cause body fluids, such as also cause body fluids, such as urine and sweat, to smell like urine and sweat, to smell like maple syrupmaple syrup

infants develop neurologic infants develop neurologic abnormalities, including seizures and abnormalities, including seizures and coma, during the first week of life coma, during the first week of life and can die within days to weeksand can die within days to weeks

In the milder forms, children initially In the milder forms, children initially appear normal but develop vomiting, appear normal but develop vomiting, staggering, confusion, coma, and the staggering, confusion, coma, and the odor of maple syrup particularly odor of maple syrup particularly during physical stress, such as during physical stress, such as infection or surgeryinfection or surgery

Infants with severe disease are Infants with severe disease are treated with dialysis. Some treated with dialysis. Some children with mild disease benefit children with mild disease benefit from injections of the vitamin B1 from injections of the vitamin B1 (thiamin). After the disease has (thiamin). After the disease has been brought under control, been brought under control, children must always consume a children must always consume a special artificial diet that is low in special artificial diet that is low in the particular amino acids that are the particular amino acids that are affected by the missing enzyme.affected by the missing enzyme.

HOMOCYSTINURIAHOMOCYSTINURIA

Children with homocystinuria are Children with homocystinuria are unable to metabolize the amino unable to metabolize the amino acid homocysteine, which, along acid homocysteine, which, along with certain toxic by-productswith certain toxic by-products

The first symptoms, including The first symptoms, including dislocation of the lens of the eye, dislocation of the lens of the eye, causing severely decreased causing severely decreased vision, usually begin after 3 vision, usually begin after 3 years of age. Most children have years of age. Most children have skeletal abnormalities, including skeletal abnormalities, including osteoporosis; the child is usually osteoporosis; the child is usually tall and thin with a curved spine, tall and thin with a curved spine, elongated limbs, and long, elongated limbs, and long, spiderlike fingers. spiderlike fingers.

In a few states, children are In a few states, children are screened for homocystinuria screened for homocystinuria at birth with a blood test. The at birth with a blood test. The diagnosis is confirmed by a diagnosis is confirmed by a test measuring enzyme test measuring enzyme function in liver or skin cells.function in liver or skin cells.

TYROSINEMIATYROSINEMIA

There are two main types of There are two main types of tyrosinemia: I and II. Type I tyrosinemia tyrosinemia: I and II. Type I tyrosinemia is most common in children of French-is most common in children of French-Canadian or Scandinavian descent. Canadian or Scandinavian descent. Children with this disorder typically Children with this disorder typically become ill sometime within the first become ill sometime within the first year of life with dysfunction of the liver, year of life with dysfunction of the liver, kidneys, and nerves, resulting in kidneys, and nerves, resulting in irritability, rickets, or even liver failure irritability, rickets, or even liver failure and death. and death.

Type II tyrosinemia is less Type II tyrosinemia is less common. Affected children common. Affected children sometimes have mental sometimes have mental retardation and frequently retardation and frequently develop sores on the skin and develop sores on the skin and eyes. Unlike type I tyrosinemia, eyes. Unlike type I tyrosinemia, restriction of tyrosine in the diet restriction of tyrosine in the diet can prevent problems from can prevent problems from developing.developing.

GLYCOGEN STORAGE GLYCOGEN STORAGE DISEASESDISEASES

There are many different glycogen There are many different glycogen storage diseases (also called storage diseases (also called glycogenoses), each identified by a glycogenoses), each identified by a roman numeral. These diseases are roman numeral. These diseases are caused by a hereditary lack of one of the caused by a hereditary lack of one of the enzymes that is essential to the process enzymes that is essential to the process of forming glucose into glycogen and of forming glucose into glycogen and breaking down glycogen into glucose. breaking down glycogen into glucose. About 1 in 20,000 infants has some form About 1 in 20,000 infants has some form of glycogen storage disease.of glycogen storage disease.

GALACTOSEMIAGALACTOSEMIA

Galactosemia (a high blood level Galactosemia (a high blood level of galactose) is caused by lack of of galactose) is caused by lack of one of the enzymes necessary for one of the enzymes necessary for metabolizing galactose, a sugar metabolizing galactose, a sugar present in lactose (milk sugar). A present in lactose (milk sugar). A metabolite builds up that is toxic metabolite builds up that is toxic to the liver and kidneys and also to the liver and kidneys and also damages the lens of the eye, damages the lens of the eye, causing cataracts.causing cataracts.

A newborn with galactosemia A newborn with galactosemia seems normal at first but within a seems normal at first but within a few days or weeks loses his few days or weeks loses his appetite, vomits, becomes appetite, vomits, becomes jaundiced, has diarrhea, and stops jaundiced, has diarrhea, and stops growing normally. White blood cell growing normally. White blood cell function is affected, and serious function is affected, and serious infections can develop. If infections can develop. If treatment is delayed, affected treatment is delayed, affected children remain short and become children remain short and become mentally retarded or may die.mentally retarded or may die.

Types and Characteristics of Glycogen Storage Diseases

Name Affected Organs Symptoms

Type O Liver, muscle Enlarged liver with accumulation of fat inside the liver cells (fatty liver); episodes of low blood sugar levels (hypoglycemia) when fasting

von Gierke's disease (Type IA)

Liver, kidney Enlarged liver and kidney; slowed growth; very low blood sugar levels; abnormally high levels of acid, fats, and uric acid in blood

Type IB Liver, white blood cells

Same as in von Gierke's disease but may be less severe; low white blood cell count; recurring mouth and intestinal infections or Crohn's disease

Pompe's disease (Type II)

All organs Enlarged liver and heart, muscle weakness

Forbes' disease (Type III)

Liver, muscle, heart, white blood cells

Enlarged liver or cirrhosis; low blood sugar levels; muscle damage and heart damage in some people

Andersen's disease (Type IV)

Liver, muscle, most tissues

Cirrhosis in juvenile type; muscle damage and heart failure in adult (late-onset) type

McArdle's disease (Type V)

Muscle Muscle cramps or weakness during physical activity

Hers' disease (Type VI)

Liver Enlarged liver; episodes of low blood sugar when fasting; often no symptoms

Tarui's disease (Type VII)

Skeletal muscle, red blood cells

Muscle cramps during physical activity; red blood cell destruction (hemolysis)

Galactosemia is treated by completely Galactosemia is treated by completely eliminating milk and milk products—eliminating milk and milk products—the source of galactose—from an the source of galactose—from an affected child's diet. Galactose is also affected child's diet. Galactose is also present in some fruits, vegetables, present in some fruits, vegetables, and sea products, such as seaweed. and sea products, such as seaweed. Doctors are not sure whether the Doctors are not sure whether the small amounts in these foods cause small amounts in these foods cause problems in the long term. People problems in the long term. People who have the disorder must restrict who have the disorder must restrict galactose intake throughout life.galactose intake throughout life.