Case StudyASSO. PROF.:Dr. SURI SIRBy:AJAY SHUKLA & HARSHRAJIT SINGH JUNEJA1ST YEAR MBBSSARASWATI MEDICAL COLLEGE

The Patient & Their SymptomsJASON, a new born baby, was healthy as can be a few days after his birth. However, after that he started showing characteristics of seizures, irritability, failure to thrive, poor suckling response, and little interest in feeding. The doctors performed an examination that showed no sign of infection and his X-rays came back normal. His parents notice a sweet smell to Jacob’s urine, and become concerned because his symptoms are eerily similar to those of an older brother that died shortly after birth. The doctors decide that additional testing should be done.

Additional Testing•Urine Analysis•Blood Analysis•White Blood Cell Analysis •Tandem Mass Spectrometry •Molecular Testing (prenatal)•Amino Acid Concentrations in Amniotic

Fluid (prenatal)

DIAGNOSIS MAPLE SYRUP URINE DISEASE.

[MSUD]

ORIGIN MSUD was reported in 1954 by

J.H.MENKES & his colleagues.The family in menke’s case study had lost four infants within the first 3 months of life to a previously underscribed degenerative disorder of nervous system.The urine of these childrens smelled like maple syrup or burned sugar,hence the disease got its name of maple syrup urine disease or MSUD.An effective treatment however had to await further biochemical analysis of the metabolic dysfunction underlying the disease.In 1960 a researcher named Dancis established that the metabolic block in MSUD is caused by deficiency of enzyme required to metabolize BCAA.

• Maple Syrup Urine Disease

• MSUD is an inherited disorder characterized by the deficiency of branched-chain alpha-keto acid dehydrogenase complex, an enzyme required to breakdown specific amino acids in the body

• Since these amino acids are not metabolized, they along with various byproducts, abnormally accumulate in the cells and fluids of the body such as brain tissue,blood.

Branched-Chain Amino Acids

• Leucine

• Isoleucine

• Valine

Maple Syrup Urine Disease• MSUD is caused by a

deficiency of the BCKD complex. This catalyzes the decarboxylation of the alpha-keto acids of leucine, isoleucine, and valine to their respective branched-chain acyl-CoAs.

• The BCKD complex has three different catalytic components (E1, E2, E3)

• Mutations in E1, E2, and E3 cause MSUD

Types of MSUD1.Classic MSUD Most common subtype of disease With less than 2% of BCKD enzyme Newborn shows symptom within 4 to 7 days of life2. Intermediate MSUD: Rare subtype Slightly higher amount of BCKD enzyme in body[3% to 8%]3. Intermittent MSUD: Second most common form of MSUD With enzyme activity b/w 8% to 15% May not show symptoms upto 12 to 24 months of age

1. :

4.Thiamine-responsive MSUD:Rare form of diseaseIn this the level of enzyme activity in child’s body is increased by giving doses of thiamine hydrochloride.

DiagnosisBefore 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 odour in the urine• Ketonuria.• It can be confirmed with an enzyme analysis.

Clinical PresentationsInitial symptoms are:

• Lethargy• Poor appetite• Weight loss• Weak sucking ability• Irritability• High-pitched cry• Irregular sleep patterns• Maple sugar odour (sweet) in urine

Clinical PresentationsSigns of intermediate and thiamine-response are:• Seizures• Neurological deficiencies• Developmental delays• Feeding problems• Poor growth• Maple sugar odour in urine

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

Treatment Options• Protein-free diet• Intravenous

administration of amino acids that don’t contain branched-chain amino acids, combined with glucose for extra calories

• Infants have a diet of formula with low levels of the amino acids leucine, isoleucine, and valine

• In extreme cases MSUD can be treated by liver translantation.

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.

ANY QUESTIONS?

Thanks for your attention!!