Maple Syrup Urine Disease

Jimale Mohamed Ali

MSUD

• Rare metabolic disorder.

• Produces urine that has maple syrup odor.

Types of MSUD

1. Classic MSUD

2. Intermediate MSUD

3. Intermittent MSUD

4. Thiamine-responsive MSUD

Epidemiology

• Incidence is approximately 1 in 185,000 infants worldwide.

• Higher incidence amongst children from consanguineous relationships.

• The rate increases to 1:176 in inbred populations, like the Mennonites.

• MSUD occurs at the same rate in males and females.

Inheritance

• Autosomal recessive• Develops from inheriting a mutated gene from each parent.• Mutations in BCKHDA(19q13.1 – q13.2), BCKDHB(6p22 –

p21, 6p14 for Ashkenazi Jews).

Pathophysiology

• Caused by mutations, or changes in the genes that are related to the BCKDC enzymes.

• When those genes are defective, the BCKDC enzymes aren’t produced or don’t work properly.

• These gene mutations are inherited on the chromosomes you receive from your parents.

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Branched-Chain Amino Acids

• Leucine

• Isoleucine

• Valine

Clinical Presentations

Initial symptoms are:

• Lethargy• Poor appetite• Weight loss• Weak sucking ability• Irritability• High-pitched cry• Irregular sleep patterns• Maple sugar odor in sweat and urine

Clinical Presentations

Signs of intermediate and thiamine-response are:• Seizures• Neurological deficiencies• Developmental delays• Feeding problems• Poor growth• Maple sugar odor in sweat and urine

Diagnosis

Before the onset of symptoms• The earlier these children are diagnosed and treated, the

less risk of permanent damage.• Newborn screening program is the most effective way to

diagnose MSUD.After onset symptoms• Maple syrup odor in the cerumen.• Ketonuria.• plasma level BCAAs, and allo-isoleucine in plasma.• It can be confirmed with an enzyme analysis.

Treatment

• It must be started as soon as possible.

• Involves a complex approach to maintain metabolic control.

• A special, carefully controlled diet is the focus of daily treatment.

• Synthetic food that strictly controls the Amino Acids leucine, isoleucine and valine.

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• Careful monitoring of protein intake.• Infant will be given an MSUD formula such as Enfamil or

Similac.• A liver transplant is an optional treatment.• In the past, dialysis was used to cleanse the body. This is no

longer used.

Complications

• Complications can be severe and even fatal.• Babies can experience metabolic crises.

Severe complications• Lack of blood flow and swelling of the brain• Seizures• Metabolic acidosis • Coma • Severe neurological damage

• Intellectual disability• Blindness

Metabolic Crises

• Is a sudden increase of BCAAs in the system. • If untreated, the situation can lead to serious physical and

neurological damage.

A metabolic crisis is indicated by:• extreme fatigue or lethargy• loss of alertness• irritability• vomiting

Prognosis

• With strict dietary compliance and good medical care, children with MSUD can, and do, lead normal lives.

• Therapy must be started at the earliest possible age to achieve the best possible outcome.

• There always remains the risk of brain injury during extended times of elevated leucine levels.

• Usually fatal within one month if left untreated.

Advice to the family of the child

• Careful control of the diet to insure the correct balance of the amino acid levels is the best strategy for the optimal function of persons with MSUD.

• MSUD is inherited in an autosomal recessive manner, so explain for the family what can happen to their future offspring.

Then?

Thanks for your attention!!