Everything you need to know about MSUD – .Maple Syrup Urine Disease

MSUD can be treatable if your child receives a newborn screening test. Below is a successful case of a British Pakistani who survived MSUD.

A Successful Screened MSUD case in Sheffield Children Hospital:

Habul Khatoon, daughter of Fehmida who lives in Birmingham was screened for MSUD in 2013. The baby girl did not cry and was constantly lethargic. She then received a newborn screening just six days after being born.

As soon as the results showed positive for MSUD at eight days old, she had to be taken into the Intensive Care Unit. Habul was put on dialysis to cleanse her blood and then began special feeds given via a feeding pump. After just 48 hours, she came out of the coma-like state and could cry normally. She is now being fed low-leucine feeds made up by her mother who has received special training on how to feed her daughter correctly. As she grows up Habul will need to have a very low protein diet avoiding eggs, fish and meats amongst other foodstuffs in order to stay well.

Dr Anupam Chakrapani, a consultant at Birmingham Children’s Hospital mentioned to The Daily Mail: ‘The expanded newborn screening project sped up the diagnosis and treatment of this rare condition and enabled Habul to recover quickly and she has remained very well.’ Mrs Khatoon added: ‘I’m very thankful. Back home in Pakistan there might be many children that pass away on a daily basis so I’m very appreciative of the program.’ Luckily for Pakistan, Zahra Beau Naqvi Foundation Welfare Trust has started Newborn Screening Lab in Pakistan.

So what is Maple Syrup Disease?

MSUD is an inherited disorder in which the body is unable to process certain protein building blocks (amino acids) properly. The condition gets its name from the distinctive sweet odor of affected infants’ urine and is also characterized by poor feeding, vomiting, lack of energy (lethargy), and developmental delay. 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 involve developmental delay and other health problems if not treated.

How common is MSUD globally?

Maple syrup urine disease affects an estimated 1 in 185,000 infants worldwide. The disorder occurs much more frequently in the Old Order Mennonite population, with an estimated incidence of about 1 in 380 newborns. In extrapolated population of 159196336, 413496 have been found to be MSUD affected in Pakistan which is a lesser number than that of 706493 prevalence rate in USA and very near to 156547 rate of UK.

If The Results Are Positive For MSUD, What Should The Screening Laboratory Team Do:

So if you are a part of a laboratory team – or if you are part of the family of the affected, you can make sure the team pays heed to the following points because this is your moral duty – follow the points below to deal with the MSUD cases successfully:

• Contact the family to inform them of the newborn screening result and ascertain clinical status (poor feeding, vomiting, lethargy, tachypnea).
• Consult with pediatric metabolic specialist.
• Evaluate the newborn (poor feeding, lethargy, tachypnea, alternating hypertonia/hypotonia, seizures). If any sign is present or infant is ill, transport to hospital for further treatment in consultation with metabolic specialist.
• Initiate timely confirmatory/diagnostic testing and management, as recommended by specialist.
• Provide the family with basic information about MSUD and dietary management.
• Report findings to newborn screening program.

How can the testing of MSUD be followed up?

Infants with mild or intermittent forms of the disorder may have totally normal blood amino acids after birth and thus can be missed by newborn screening. A diagnosis may be suspected based upon symptomatic findings (lethargy, failure to thrive, neurologic signs or, during a metabolic crisis, odor of maple syrup in earwax, sweat or urine). Tests to diagnose MSUD may include urine analysis to detect high levels of keto acids (ketoaciduria) and blood plasma analysis to detect abnormally high levels of amino acids.

It will also involve checking your baby’s urine and blood samples for harmful amounts of acids and toxins. Certain acids and toxins build up in the body when a child has an amino acid condition, so measuring the amounts of these substances in your baby’s body can help doctors determine if your baby has a condition. High amounts of branch-chained amino acids in the blood and ketones in the urine might indicate that your baby has MSUD.

Other Alternatives of Screening:

• Genetic Counseling: carrier testing for relatives at increased risk and prenatal diagnosis for pregnancies at increased risk are possible if the disease-causing mutations have been identified in an affected family member.
• Prenatal diagnosis: It can be performed by enzyme testing on cultured amniocytes or chorion villus cells.
• A bacterial inhibition method: Thin layer chromatography and tandem mass spectrometry are all able to detect an increase in leucine, isoleucine and allo-isoleucine.
• Ketonuria Test: can be detected by standard urine test strips; ketonuria in a newborn should always be followed by investigation for metabolic disorders.
• *Plasma Amino Acids: elevation of BCAAs. Detection of allo-isoleucine (may not appear until the sixth day of life) is diagnostic.
• *Urine test: organic acids by gas chromatography-mass spectrometry: for the detection of alpha-hydroxyisovalerate, lactate, pyruvate and alpha-ketoglutarate.
• Enzyme Activity can be measured in lymphocytes and/or cultured fibroblasts, although this test is not necessary for diagnosis.

*Amino acids and urine tests are available at AFIP, Rawalpindi.

How MSUD should be treated:

The baby may need to be on a protein-restricted diet to avoid foods containing proteins that your baby’s body cannot break down. A dietician can help you plan the best diet for your child. Special formulas and foods for children with maple syrup urine disease (MSUD) are also available. These formulas will likely need to continue through adulthood.

SUPPLEMENT:

1. Thiamine supplements: Thiamine supplements are helpful for some children with MSUD. Your baby’s doctor will be able to determine if your baby has a type of MSUD that is considered “thiamine-responsive” and write an appropriate prescription.
2. One example of a supplement is,

Ketonex-1:

FEATURES

• Branched-chain amino acid-free to allow greater intake of intact protein.
• L-carnitine (100 mg/100 g) and taurine (40 mg/100 g) to help supply amounts normally found in human milk and foods of animal origin.
• Approximately 40% of energy as fat to help achieve acceptable formula osmolality.
• 6% of energy as linoleic acid.
• Nutrient profile specifically designed for infants and toddlers.
• When fed according to the Abbott Nutrition Support Protocols, provides adequate amounts of all nutrients.
• Halal (Muslims can consume it)
• Lactose-free.
• Gluten-free.

To meet the nutrient needs of the infant or child, infant formula, breast milk or additional food choices must be given to supply protein, isoleucine, leucine and valine requirements. These may be added to the Ketonex-1 mixture or prepared separately as instructed. Depending on the specific needs of each patient, preparation will vary as prescribed by physician.

PRECAUTIONS

• Give only to infants and toddlers with proven maple syrup urine disease who are under medical supervision. Must be supplemented with protein and fluid in prescribed amounts to completely meet isoleucine, leucine, valine and water requirements.
• Not intended as a sole source of nutrition.
• Not for IV use.
• Do not boil mixture or use terminal sterilization.
• Never use a microwave oven to warm formula. Serious burns can result.
• Powdered infant formulas are not sterile and should not be fed to premature infants or infants who might have immune problems unless directed and supervised by your baby’s doctor.

 

Are there any therapies for MSUD available?

Liver transplantation has been used to treat individuals with classic MSUD. This procedure has resulted in individuals who are symptom-free and able to eat protein-rich foods. The new liver supplies enough of the enzymes needed to breakdown the three amino acids that accumulate in MSUD. However, availability of a donor liver and the high cost are hurdles to this procedure. For those that do undergo transplantation, success rates are very high. University of Pittsburgh Children’s Hospital and the Clinic for Special Children conducted a collaborative study involving 52 liver transplants between 2004 and 2013. Of these 52, 100% of the patients had disease-free survival and graft survival. More research is necessary to determine the long-term effects of liver transplantation on neurological development in individuals with MSUD.

What outcomes should one expect after treatment?

• If maple syrup urine disease (MSUD) is treated early, children can have healthy growth and development.
• Some children may still experience signs of MSUD even with treatment.
• It is important to treat MSUD because babies who do not receive treatment are at risk for brain damage, coma, or death.