ß-Ketothiolase Deficiency, Metabolic Disorder, Organic acid condition Screening -Infant

ß-Ketothiolase Deficiency, Metabolic Disorder, Organic acid condition Screening -Infant

ß-Ketothiolase Deficiency, Metabolic Disorder, Organic acid condition Screening

Summary of Recommendation and Evidence

Population

Recommendation

Grade
(What's This?)

Screening of both Genders

The genetic screening for ß-Ketothiolase Deficiency is recommended.

B

Beta-ketothiolase deficiency is a rare, autosomal recessive metabolic disorder in which the body cannot properly process the amino acid isoleucine or the products of lipid breakdown.

The typical age of onset for this disorder is between 6 months and 24 months.

OVERVIEW

Due to absence of the enzyme mitochondrial acetoacetyl-CoA thiolase, patients are unable to break down the amino acid isoleucine. The breakdown of ketone bodies is also causing a buildup of organic acids and a decreased ability to generate energy. Patients typically present with metabolic acidosis induced by fasting, infection, fever or vomiting.

SCREENING

Finding

Elevated C5-OH (2-methyl-3-hydroxybutyrylcarnitine), elevated C5:1 (tiglycarnitine)

Tested By

Tandem mass spectrometry (MS/MS); sensitivity=NA; specificity=NA

PREVALENCE

Rare 

INHERITANCE

BKD  is inherited in an autosomal recessive manner. It affects both boys and girls equally.

PRENATAL TESTING

DNA testing possible by amniocentesis or chorionic villus sampling (CVS) if both disease causing mutations of an affected family member have been identified.

CLINICAL CHARACTERISTICS

With treatment, normal development can be expected with avoidance of severe recurrent metabolic crises. Without treatment, outcomes can vary widely due to broad clinical heterogeneity, with death or severe neurologic impairment possible, particularly in those with severe episodes in infancy. Age of symptom onset is variable, ranging from 3 days to 4 years, with the mean age at presentation of 15 months. Symptoms may be triggered by fasting and illness. 

Initial signs/symptoms may include:

  • feeding problems
  • vomiting, possibly with hematemesis
  • diarrhea
  • lethargy progressing to coma
  • hypoglycemia or occasionally hyperglycemia

 

If not treated promptly, patients may experience:

  • acute metabolic acidosis
  • failure to thrive
  • intellectual disability
  • death

EARLY SIGNS

Signs of beta-ketothiolase deficiency (BKT) usually start around 1 year of age, though this can range from 6 months to 2 years.

Signs of BKT include:

  • Sleeping longer or more often 
  • Tiredness
  • Vomiting
  • Diarrhea
  • Fever
  • Poor appetite
  • Breathing trouble

Many of these signs may occur when your baby eats foods that his or her body cannot break down. They can be triggered by long periods of time without eating, illnesses, and infections.

CAUSES

The enzymes in your baby’s body help break down foods. Enzymes break down proteins into their building blocks, amino acids. Other enzymes then break down the amino acids.

In beta-ketothiolase deficiency (BKT), your baby’s body either does not make enough or makes non-working mitochondrial acetoacyl-CoA thiolase (MAT) enzymes. MAT is in charge of breaking down the amino acid isoleucine. If MAT does not work, then isoleucine cannot be digested and harmful substances build up in the body.

BKT is an autosomal recessive genetic condition. This means that a child must inherit two copies of the non-working gene for BKT, one from each parent, in order to have the condition. The parents of a child with an autosomal recessive condition each carry one copy of the non-working gene, but they typically do not show signs and symptoms of the condition. While having a child with BKT is rare, when both parents are carriers, they can have more than one child with the condition.

TREATMENT

Dietary Treatment

The most important treatment for your baby is a carefully planned diet. Your baby will need a restricted diet in order to avoid too many harmful proteins. A  nutritionist or dietician can help you plan a low-protein diet that still gives your baby the nutrients he or she needs for healthy development.

Eating often will also help prevent your baby from experiencing many of the signs mentioned in the Early Signs section. Illnesses and infections can also trigger these signs.

Supplements and Medications

Supplements can also help balance your baby’s digestive system. L-carnitine is a natural substance, but your baby’s body might not make enough of it. L-carnitine supplements can help remove toxic substances from the body. Your baby’s doctor will need to write a prescription for these supplements.

Bicitra is another medical supplement that your baby’s doctor might prescribe. Bicitra helps balance the acid levels in the blood. Babies with BKT have high levels of acid in their blood. While it is normal to have some acid in the blood, very high acid levels can be toxic.

EXPECTED OUTCOMES

With early treatment, your baby can have healthy growth and development.

There are some cases where children show signs of beta-ketothiolase deficiency (BKT) even with treatment. However, these signs usually decrease with age.

If BKT is not treated, children can develop intellectual disabilities and seizures.