Inborn errors of metabolism

Overview of some inborn errors of metabolism along with dietary management.

1. Inborn errors of Metabolism BY: AKANSHA BHATNAGAR

2. Introduction Inborn errors of metabolism are rare genetic (inherited) disorders in which the body cannot properly turn food into energy. The disorders are usually caused by defects in specific proteins (enzymes) that help break down (metabolize) parts of food. A food product that is not broken down into energy can build up in the body and cause a wide range of symptoms. Several inborn errors of metabolism cause developmental delays or other medical problems if they are not controlled.

3. Garrod Hypothesis The one gene-one enzyme hypothesis was first proposed by the English physician Archibald Garrod in 1909. It suggests that each  gene codes for a single, specific  enzyme . In other words, under this hypothesis, each gene would be responsible for the enzyme facilitating a single step in a metabolic process and the inherited disorders result from reduced activity or complete absence of  enzymes  involved in certain biochemical pathways. 

4. GALACTOSEMIA Galactosemia is a family of genetic disorders that result from compromised ability to metabolize the sugar galactose ; the term “ galactosemia ” literally means too much galactose in the blood. The different types of galactosemia include: Classic and clinical variant galactosemia (aka Type 1 galactosemia ) Duarte variant galactosemia Galactokinase deficiency (aka Type 2 galactosemia ) Epimerase deficiency (aka Type 3 galactosemia ) Galactosemia prevents a person from processing the sugar galactose , which is found in many foods. Galactose also exists as part of another sugar, lactose, found in all dairy products. Normally when a person consumes a product that contains lactose, the body breaks the lactose down into galactose and glucose. In Galactosemia galactose builds up in the blood. This accumulation of galactose can cause serious complications such as: an enlarged liver kidney failure cataracts in the eyes brain damage.

5. PHENYLKETONURIA (PKU) Phenylketonuria  (commonly known as PKU) is an inherited disorder that increases the levels of a substance called phenylalanine in the blood. Phenylalanine is a building block of proteins (an amino acid) that is obtained through the diet. It is found in all proteins and in some artificial sweeteners. If PKU is not treated, phenylalanine can build up to harmful levels in the body, causing intellectual disability and other serious health problems. The signs and symptoms of PKU vary from mild to severe. The most severe form of this disorder is known as classic PKU. Infants with classic PKU appear normal until they are a few months old. Without treatment, these children develop permanent intellectual disability. Seizures, delayed development, behavioral problems, and psychiatric disorders are also common. Untreated individuals may have a musty or mouse-like odor as a side effect of excess phenylalanine in the body. Children with classic PKU tend to have lighter skin and hair than unaffected family members and are also likely to have skin disorders such as eczema. Less severe forms of this condition, sometimes called variant PKU and non-PKU hyperphenylalaninemia , have a smaller risk of brain damage. People with very mild cases may not require treatment with a low-phenylalanine diet.

6. TYROSINEMIA Tyrosinemia  is a genetic disorder characterized by disruptions in the multistep process that breaks down the amino acid tyrosine, a building block of most proteins. If untreated, tyrosine and its byproducts build up in tissues and organs, which can lead to serious health problems. There are three types of  tyrosinemia , which are each distinguished by their symptoms and genetic cause.  Tyrosinemia  type I, the most severe form of this disorder, is characterized by signs and symptoms that begin in the first few months of life. Affected infants fail to gain weight and grow at the expected rate (failure to thrive) due to poor food tolerance because high-protein foods lead to diarrhea and vomiting.  Tyrosinemia  type II can affect the eyes, skin, and mental development. Signs and symptoms often begin in early childhood and include eye pain and redness, excessive tearing, abnormal sensitivity to light (photophobia), and thick, painful skin on the palms of their hands and soles of their feet ( palmoplantar hyperkeratosis). Tyrosinemia  type III is the rarest of the three types. The characteristic features of this type include intellectual disability, seizures, and periodic loss of balance and coordination (intermittent ataxia).

7. Maple Syrup Urine Disease (MSUD) Maple syrup urine disease is an inherited disorder in which the body is unable to process certain protein building blocks ( leucine , isoleucine and valine ) properly. The condition gets its name from the distinctive sweet odor of affected infants' urine. It is also characterized by poor feeding, vomiting, lack of energy (lethargy), abnormal movements, and delayed development. If untreated, maple syrup urine disease can lead to seizures, coma, and death. Maple syrup urine disease is often classified by its pattern of signs and symptoms. The most common and severe form of the disease is the classic type, which becomes apparent soon after birth. Variant forms of the disorder become apparent later in infancy or childhood and are typically milder, but they still lead to delayed development and other health problems if not treated. Special feeds containing energy and proteins without the branched chain amino acids can be give to the infants.

8. HOMOCYTINURIA Homocystinuria  is an inherited disorder in which the body is unable to process certain building blocks of proteins ( amino acids ) properly. There are multiple forms of  homocystinuria , which are distinguished by their signs and symptoms and genetic cause. The most common form of  homocystinuria  is characterized by  nearsightedness  ( myopia ), dislocation of  the lens  at the front of the eye, an increased risk of abnormal blood clotting, and brittle bones that are prone to fracture ( osteoporosis ) or other skeletal abnormalities. Some affected individuals also have developmental delay and learning problems. Less common forms of  homocystinuria  can cause intellectual disability, failure to grow and gain weight at the expected rate (failure to thrive), seizures, problems with movement, and a blood disorder called  megaloblastic  anemia . Megaloblastic anemia occurs when a person has a low number of red blood cells (anemia), and the remaining red blood cells are larger than normal ( megaloblastic ). The signs and symptoms of  homocystinuria  typically develop within the first year of life, although some mildly affected people may not develop features until later in childhood or adulthood.

9. GALACTOSEMIA Galactosemia  is a disorder that affects how the body processes a simple sugar called galactose . A small amount of galactose is present in many foods. It is primarily part of a larger sugar called lactose, which is found in all dairy products and many baby formulas. The signs and symptoms of  galactosemia  result from an inability to use galactose to produce energy. Researchers have identified several types of  galactosemia . These conditions are each caused by mutations in a particular gene and affect different enzymes involved in breaking down galactose . Classic  galactosemia , also known as type I, is the most common and most severe form of the condition. If infants with classic  galactosemia  are not treated promptly with a low- galactose diet, life-threatening complications appear within a few days after birth. Affected infants typically develop feeding difficulties, a lack of energy (lethargy), a failure to gain weight and grow as expected (failure to thrive), yellowing of the skin and whites of the eyes (jaundice), liver damage, and abnormal bleeding. Other serious complications of this condition can include overwhelming bacterial infections ( sepsis ) and shock. Affected children are also at increased risk of delayed development, clouding of the lens of the eye ( cataract ), speech difficulties, and intellectual disability. Females with classic  galactosemia  may develop reproductive problems caused by an early loss of function of the ovaries (premature ovarian insufficiency).

10. Galactosemia  type II (also called galactokinase deficiency) and type III (also called galactose epimerase deficiency) cause different patterns of signs and symptoms.  Galactosemia  type II causes fewer medical problems than the classic type. Affected infants develop cataracts but otherwise experience few long-term complications. The signs and symptoms of  galactosemia  type III vary from mild to severe and can include cataracts, delayed growth and development, intellectual disability, liver disease, and kidney problems.

11. NUTRITION THERAPY

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