Inborn Errors of Metabolism

Why ‘Inborn Errors of Metabolism’ is a Concern to Newborn ?

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.

It is rare, but the diseases with which they are associated often have a significant impact on growth, development, and long-term health of affected children. Early recognition and intervention (when possible) are essential to avoiding disastrous consequences associated with these diseases. Some disorders arise as a result of mutations to catabolic pathways involving lysosomal storage and macromolecule degradation.

They are mainly of five types.

  • Phenylketonuria(PKU)
  • Tyrosinemia
  • Maple Syrup Urine Dieases (MSUD)
  • Phenylketonuria(PKU)
  • Galactosemia

Lets get into this in details.

PHENYLKETONURIA

The essential amino acid  is utilized for tissue protein synthesis and hydroxylated to        tyrosine. The hydroxylation reaction requires  hydroxylase. Phenylketonuria  is a group of inherited disorders of phenylalanine metabolism caused by impaired phenylulanine hydroxylase activity. PKU cannot break down  into another amino acid, tyrosine. Phenylalanine builds up in the bloodstream and causes brain damage.

Accumulation of phenylalanine and its catabolic products leads to central nervous  damage. The extent of  damage caused to the brain depends on the time at which the insult occurs. Deficient myelination and abnormalities in brain proteolipids and proteins occur in late gestation and during first 6 to 9 months of In the fully matured brain, the synthesis of neurotransmitters is affected. This might cause nerve degeneration, behavioural difficulties and delayed development.

Clinical Manifestations

  • Phenylketonuria , commonly referred to as PKU, occurs at the age of 3 to 6 months
  • It is characterized by develop mental delay, microcephaly (abnormally small head),
  • Abnormal electro-encephalogram,
  • Eczema,
  • Musty odour and hyper activity.

Lofenalac

Lofenalac is a formula which is nutritionally complete except for phenylalanine. This formula is the main diet for the infants suffering from PKU. The diet should be progressed as for a normal infant and child. Utmost careshould be taken while introducing new foods to them. Effort should be taken to develop a variety of recipes using foods low in phenylalanine.

Phenylalanine is found in milk, cheese, eggs, fish, meat, beans, nuts, and infant formulas (both regular and soy), and to a lesser extent in cereals, vegetables and fruit. People with PKU cannot break down phenylalanine into another amino acid, tyrosine. Phenylalanine then builds up in the bloodstream and causes brain damage as you learnt earlier. To avoid  a person can eat a healthy diet that includes a low-phenylalanine formula, fruits, vegetables, sugars and other low-protein foods.

Target Your Phenyl Free Food Choice

Inborn Errors of Metabolism

TYROSINEMIA

Tyrosinemias, as the name  suggests, are due to defects  in  tyrosine catabolism. Depending on which enzyme is absent/defective, different kinds of symptoms appear.
Accordingly, three distinct defects have been identified.

• •Tyrosinemia-I •This occurs due to the deficiency of the enzyme fimaryl acetoacetate hydrolase .Failure to properly break down tyrosine leads to an abnormal accumulation of tyrosine and its metabolites in the liver, resulting in severe liver disease. There is a progressive liver and kidney failure in this disease and hence is also called hepatorenal tyrosinemia.

• •Tyrosinemia-II •This condition is caused by deficiency of hepatic tyrosine aminatransferase (also commonly called tyrosine transaminase). It catalyzes the first step in the catabolism of tyrosine forming the corresponding keto acid, p-hydroxy phenyl pyruvic acid.There is moderate mental retardation. Tyrosine and phenylalanine restricted diet is essential.

• •Neonatal Tyrosinemia •In neonatal tyrosinemia, the defective enzyme is p-hydroxy phenyl pyruvichydroxylase which normally converts p-hydroxy phenyl pyruvic acid to homogentisic acid. The condition is asymptomatic and is more common in premature infants.

Foods to be Avoided in Tyrosinemia

  • Foods that all children with tyrosinemia should avoid are foods rich in protein meat, chicken, fish, milk, cheese, beans and legumes, peanut butter, and eggs.
  • Foods with moderate amounts of protein can be eaten in limited amounts. These foods include grains, bread, pasta, rice, potatoes, corn, and peas.
  • Foods with little or no protein. These foods include most fruits and vegetables. Low protein products, including bread, pasta, noodles, rice etc. may also be used. Therefore, we may conclude by saying that bread, cereals, fruits and vegetables and fats are allowed.
  • A high carbohydrate feed, providing 65-75% of calories may be recommended.

MAPLE SYRUP URINE DISEASE(MSUD)

Maple Syrup Urine Disease (MSUD) is a rare genetic disorder where the body is unable to metabolise three branched chain amino acids namely leucine, isoleucine and valine due to the deficiency of an enzyme complex(branched chained alpha keto dehydrogenase) .

These three aminoacids are normally metabolised to ketoacids and then decarboxylated simple acids. In MSUD disorder an oxidative decarboxylase in the white blood cells  is missing. Since the carboxyl groups can not be removed there is an accumulation of branched chain ketoacids and their amino acid precursors.

The branched chain α-ketoacids are relatively acute neurotoxin and probably interfere with oxygen, consumption and ATP production in the medullary reticular substance of the brain.

There is a progressive neurologic dysfunction and production of fragrant urine with odour of burnt sugar or maple syrup.

Clinical Manifestation

  • Neurologic impairment in the new born is by poor sucking,
  • Intermittent periods of rigidity and flaccidity.
  • Impaired enzyme deficiency,
  • Seizures,
  • Apnea (brief pause in breathing) ,
  • Death may occur

The Diet Of A MSUD Patient (Child) Should Therefore Involve

  • Measured quantities of natural protein or leucine from foods.
  • A BCAA free protein, vitamin and mineral supplement.
  • The natural protein and vitamin/mineral supplement should ideally be evenly distributed through the day to allow maximum utilization of the amino acids for protein anabolism, for tolerance of the supplement.
  • Free foods that are low in BCAA including sugars, fats and oils, as well as, foods specifically produced for a low protein diet(bread,biscuits, pastas elc.) and suppleinents be given.
  • Supplements of valine and/or isoleucine are helpful.

HOMOCYSTINURIA

Homocystinuria may result from errors of methionine metabolism. This produces defects  in  the function of cystathione b synthase or 5-methyltetrahydrofolate homocysteine methyltransferase.

The most common form of homocystinuria is caused by a deficiency of the enzyme cystathionine b synthase. This enzyme is essential for the conversion of homocysteine to cystathionine.

Severely impaired enzyme function produces accumulation of plasma homocysteine  and  methionine and decreased cysteine in cells.

Large amounts of homocystine are excreted  in  the urine. If this is unattended  early’in  life, skeletal changes, dislocated lenses,intravascular thrombosis, osteoporosis and mental retardation might occur.

Therapeutic  dose of pyridoxine (1 gm/day) is usually tried in all palients with hypermethioninernia and homocystinemia.

For patients who do not respond to pyridoxine,methionine restricted diet supplemented with L-cysteine is used.

Foods And Food Items Containing Varying Levels Of Methionine

GALACTOSEMIA

Galactosemia is a genetic disorder caused by deficient functioning of three enzymes namely:-

  • galactokinase,
  • galactose -1 phosphate uridyl transferase
  •  UDP galactose  4-epimerase.

Galactose derived from the hydrolysis of lactose in the intestine is absorbed normally. But in the absence of gal-1-P-transferase it leads to the accumulation of galactose, galactose-1-phosphate, and galactitol in the blood and tissues. Accumulation of these has been attributed to many of the negative effects of Galactosemia (GALT deficiency or Galactose 1 phosphate uridylytransferase deficiency), galactokinase deficiency and epimerase deficiency with glucose.

Cataract

Inborn Errors of Metabolism

Patients with galactokinase deficiency suffer only from cataract, Galactitol accumulates in the lens of the eye creating an osmotic gradient that allows the glutathione from the lens to efflux. Due to this the concentration of glutathione in the lens is decreased.Glutathione peroxidase and hydrogen peroxidase are inactivated .As a result hydrogen peroxide accumulates in the lens denaturing the proteins of the lens. This leads to the production of lenticular cataracts. Some infants are born with cataract, jaundice and cirrhosis.

Diet Therapy

Treatment should begin in the first few days of life itself. The goal of dietary treatment for galactosemia is to minimize galactose intake which in turn minimizes galactose-1-phosphate production. Therefore, dietary treatment of galactosemia is to remove any foods containing galactose from the diet. Because milk and milk products are the must common food source of galactose ,persons with galactosemia should avoid these foods

Range

Diagnosis of  galactosemia is  by  measuring the activity of gal-1-transferase  in erythrocytes. Galactose should be restricted if the gal-1-transferase  is elevated above 2 mg/dl.

Galactose content of some common foods

Video

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Kanchan shaw
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Kanchan shaw
11 months ago

Nice mam

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