Metabolic Disorder Essay: Maple Syrup Urine Disease (MSUD)

This essay provides a comprehensive overview of Maple Syrup Urine Disease (MSUD), a genetic metabolic disorder characterized by the deficiency or absence of the branched-chain alpha-keto acid dehydrogenase complex. The essay begins with a description of the normal metabolic pathway involving the oxidative decarboxylation of branched-chain amino acids (BCAAs) – isoleucine, leucine, and valine. It then details the origin of MSUD, including the specific genes (BCKDHB, BCKDHA, and DBT) and mutations involved, highlighting the inherited nature of the disease. The consequences of these mutations at the metabolic level are discussed, focusing on the accumulation of BCAAs and their byproducts, which can lead to severe health complications, particularly affecting the brain and other organs. The essay also covers the signs and symptoms of MSUD, which vary depending on the severity and age of onset, the prevalence of the disease globally and in Australia, the methods used for detection, including newborn screening and urine analysis, and the various therapeutic interventions available for managing the disorder, such as lifelong dietary management and immediate medical interventions for metabolic crises. References to relevant scientific literature support the information presented.

Maple Syrup Urine Disease (MSUD)
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Description of normal metabolic pathway
Maple syrup urine disease refers to a disorder that come as a result of deficiency or absence of
branched-chain alpha-keto acid dehydrogenase complex (1). The branched-chain alpha-keto acid
dehydrogenase complex contains a multi subunit complex enzymes from the inner membrane of
mitochondria. The role of these enzymes is to act as catalyzers during oxidative decarboxylation
of the branched and short-chain alpha-ketoacids (3). However, when this metabolic process fail
to occur, the outcome is the accumulation of all the three BCAAs and other byproducts across
the body. The three main BCAAs include Isoleucine, Leucine and Valine. There are cases where
MSUD disorder is a severe at start appearing at birth. During such circumstance, the
concentration of BCAAs continue in plasma in a period of 48 hours after birth.
Origin of MSUD
MSUD is inherited from one family member to another (2). During mutation, the may fail to
process specific amino acids accurately. The main genes involved during mutation are
BCKDHB, BCKDHA and DBT. The role of these three genes is to provide crucial information
for making proteins that coordinate as part of a complex. Consequently, the protein complex is
the one that plays role of breaking down isoleucine, valine and leucine amino acids.
Consequences at the metabolic level
When mutations occurs in any of these three genes, reduces the operation of the protein complex.
The outcome is abnormal it hinder the breakdown of isoleucine, valine and leucine (5). The
failure of this process is what lead to accumulation of byproducts and amino acids in the body.
Consistent accumulation of these byproducts is unhealthy to human body as they can affect other
organs such as brain and heart. However the serious challenge is the Mable syrup urine disease.
Major signs and symptoms of MUSD
The signs and symptoms of MUSD vary from one patient to another at its early stage. One of the
main factors that determine signs and symptoms is the amount of the residual enzyme activity.
When this disorder develop in infants, they start exhibiting signs within a period of three days.
Some of the signs and symptoms in infants include consistent irritation, poor breast feeding
habit. However, when the disorder develops, the infants start developing signs such as athetoid,

increasing hypertonia and lastly coma (4). As the child grows neurologic function may fail. The
later stages are accompanied by failure in respiratory system and even death can result.
Generally, the common signs of this disease include abnormal movement, poor feeding whether
on bottle or breast, delay in development, lethargy and vomiting. Even though this disorder can
be treated, there are other life-long threats that the patient must get ready to encounter. One of
the main threat is the recurrent metabolic decomposition (4). The reason why this threat occurs is
due to increased breakdown of proteins from various metabolic stresses. Such activity may take
place even when the patient have changed diet. If MUSD become severe in an individual, other
complications that rise include loss of the bone mass and inflammation of the pancreas.
Prevalence of the disease in the world and Australia.
In every 190,000 infants that are born across the globe, one is infected with maple syrup urine
disorder (6). However, the disorder is frequent in the old order Mennonite people. The Old Order
Mennonite always register one infected child in every three hundred and fifty births. However,
the disease is always rare in Australia with less than one percent of babies born in Australia show
MUSD.
The mode of detection and its prognosis.
MUSD is always detected through the newborn screening process. Nurses make use of Tandem
mass spectrometry (3). The tool is advanced and it can test more than 20 disorders from a child’s
blood sample. However, the process may not be accurate for MUSD. In some cases, infants may
have mild forms of the disorder and exhibit normal blood amino acids. It is usually important to
base the decision using the symptomatic findings. Urine analysis is important when testing for
MUST. The analysis can detect the exceeding level of the keto acids in the body (2). Apart from
the urine analysis another important issue is enzymatic diagnosis. The diagnosis can be done by
examining the white blood cells of the infant. The other method is molecular genetic analysis for
mutations that occurred in DBT, BCKDHA, and BCKDHB. The early analysis of these elements
helps in the management of the disease. There are multiple therapies that doctors can do to
manage and treat the disorder. One of the choices available is lifelong therapy. The role of this
therapy is to maintain the available amino acids in the body.it reduces serious health

complication that the victim would have gone through. In other cases, doctors can do immediate
medical interventions for the metabolic challenge.

References
1. Blackburn PR, Gass JM, e Vairo FP, Farnham KM, Atwal HK, Macklin S, Klee EW,
Atwal PS. Maple syrup urine disease: mechanisms and management. The application of
clinical genetics. 2017;10:57.
2. Cheng A, Han L, Feng Y, Li H, Yao R, Wang D, Jin B. MRI and clinical features of
maple syrup urine disease: preliminary results in 10 cases. Diagnostic and Interventional
Radiology. 2017 Sep;23(5):398.
3. Feier F, Schwartz IV, Benkert AR, Neto JS, Miura I, Chapchap P, da Fonseca EA, Vieira
S, Zanotelli ML, e Vairo FP, Camelo Jr JS. Living related versus deceased donor liver
transplantation for maple syrup urine disease. Molecular genetics and metabolism. 2016
Mar 1;117(3):336-43.
4. Grünert SC, Rosenbaum-Fabian S, Schumann A, Schwab KO, Mingirulli N,
Spiekerkoetter U. Successful pregnancy in maple syrup urine disease: a case report and
review of the literature. Nutrition journal. 2018 Dec 1;17(1):51.
5. MacGloin H, Guilder L, Cleary M, Davison J, Uudelepp M, Chakrapani A. G262 Maple
syrup urine disease (MSUD) referred to tertiary services before and after newborn
screening (NBS). Archives of Disease in Childhood. 2019 May 1;104(Suppl 2):A106.
6. Saeed HA. Maple Syrup Urine Disease with Concomitant Congenital Adrenal
Hyperplasia in a Setting of Consanguineous Marriage. Journal of Rawalpindi Medical
College. 2018 Sep 30:296-7.