Homocystinuria, Metabolic Disorder, Amino acid disorder Screening -Infant

Homocystinuria, Metabolic Disorder, Amino acid disorder Screening -Infant

Homocystinuria, Metabolic Disorder, Amino acid disorder Screening

Summary of Recommendation and Evidence

Population

Recommendation

Grade
(What's This?)

Screening of both genders

The genetic screening for Homocystinuria is recommended.

B

Homocystinuria is a rare metabolic condition characterized by an excess of the compound homocystine in the urine. The condition may result from deficiency of any of several enzymes involved in the conversion of the essential amino acid methionine to another amino acid (cysteine)--or, less commonly, impaired conversion of the compound homocysteine to methionine.

OVERVIEW

A deficiency of cystathionine beta-synthase (CBS) results in the inability to degrade homocystine to cystathionine, resulting in increased levels of homocysteine and methionine. A variant that represents a minority of cases is responsive to vitamin B6 (pyridoxine), but this type may be missed by newborn screening. Elevated homocysteine impairs the function of several proteins (including fibrillin) interfering with the formation of disulfide bonds and impairs endothelial function, leading to thrombosis.

SCREENING

Finding

Elevated methionine

Tested By

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

PREVALENCE

About 1:200,000 - 1:300,000 live births, as high as 1:65,000 in Ireland 

INHERITANCE

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

PRENATAL TESTING

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

CLINICAL CHARACTERISTICS

With treatment normal IQ is possible and reduction of thromboembolic events may decrease the incidence of other sequelae, such as ectopia lentis, seizures, and psychiatric problems. Without treatment, symptoms vary widely and may present at different ages, ranging from lens dislocation, poor vision, developmental delays, marfanoid habitus, and acute thromboembolism. 

Initial symptoms in infants and toddlers may include:

  • Developmental delay
  • Emotional and behavior problems
  • Thromboembolism
  • Ectopia lentis (dislocation of the ocular lens) or severe myopia (nearsightedness)

 

Findings in older children and adults may include:

  • Marfanoid habitus: tall/ thin build; long fingers, arms, and legs
  • Genu valgum, pes cavus
  • Osteoporosis
  • Malar flush
  • Decreased hair, skin, iris pigmentation
  • Seizures
  • Vascular disease and stroke
  • Psychiatric abnormalities
  • Mental retardation

EARLY SIGNS

Babies with homocystinuria (HCY) are usually healthy at birth. Early screening and treatment can often prevent the signs and symptoms of HCY. If children are not treated, signs of HCY usually begin between ages one and three. The signs and symptoms are highly variable among individuals with HCY. Your baby may have many of these signs or none at all.

Signs of HCY may include:

  • Poor growth
  • Trouble gaining weight
  • Developmental delays
  • Behavioral difficulties
  • Weak muscle tone (also known as hypotonia)
  • Pale skin and hair
  • Seizures (Epilepsy)

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

When we eat food, enzymes help break it down. Some enzymes help break down proteins into their building blocks, called amino acids. Other enzymes break down these amino acids. In homocystinuria (HCY), the enzymes that break down the amino acids methionine and homocysteine are not working correctly.

In most cases of HCY, the enzyme cystathionine beta-synthase (CBS) is not working. After methionine is broken down into homocysteine, CBS helps to break down homocysteine.

If your baby’s body has non-working copies of CBS, then homocysteine cannot be broken down. This causes high levels of methionine and homocysteine to build up in the body. Everyone has these substances in his or her blood, but high levels can be toxic.

HCY is an autosomal recessive genetic condition. This means that a child must inherit two copies of the non-working gene for HCY, 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 HCY is rare, when both parents are carriers, they can have more than one child with the condition. 

TREATMENT

Dietary Treatment

Your baby may need to be on a restricted diet to avoid foods containing methionine, a substance in proteins, which individuals with homocystinuria (HCY) cannot break down. A dietician or nutritionist can help you plan an appropriate diet for your child.

Your baby’s doctor might also recommend special formulas and foods for children with HCY. These formulas will likely need to continue through adulthood.

Supplements and Medications

Certain types of homocystinuria (HCY) can be treated with prescription vitamin B6 supplements. These natural supplements may reduce or prevent some of the health complications commonly associated with HCY, such as blood clots, eye problems and learning and intellectual disabilities. Your baby’s doctor may be able to perform tests to determine if your baby will benefit from vitamin B6 supplements and write an appropriate prescription.

Betaine and folic acid are other natural vitamin supplements that can help lower the dangerously high homocystine levels in individuals with HCY. Your baby’s doctor can also write a prescription for these supplements. 

Vitamin B12 injections or L-cysteine supplements may help your child if he or she has low levels of these substances due to HCY. Vitamin B12 is a natural vitamin, and L-cysteine is a substance found in proteins. Talk to your baby’s healthcare provider before starting this type of treatment.

EXPECTED OUTCOMES

With early and on-going treatment, children with homocystinuria (HCY) can have healthy growth and development. Treatment can reduce the chances for developing blood clots, vision trouble, heart disease, and strokes. This is why it is important to have newborn screening for HCY.

Some children who receive treatment still experience vision trouble, but this can be corrected.

Children who do not receive treatment for HCY may develop behavioral difficulties, learning disabilities, or intellectual disabilities.