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Maple Syrup Urine Disease

March 30th, 2016

Maple Syrup Urine Disease

Maple Syrup Urine Disease (MSUD)

Maple Syrup Urine Disease refers to an inherited metabolic condition in which the body fails to actively metabolize certain amino acids from the system due to absence or defects of enzymes. The spillage of poorly degraded amino acids imparts a distinct smell to the urine; thereby leading to maple syrup urine disease (also known as branched-chain ketonuria I or branched-chain ketoaciduria).

According to a new study, the prevalence of MSUD in general population is one in 185,000 (1). The incidence is much higher in certain communities such as Mennonites, where one in 176 babies are born with this condition.

Causes Of Maple Syrup Urine Disease

Amino acids are the end- products of degradation of dietary protein due to enzymatic processes. Inefficiency, defects or total absence of vital enzymes can impede the protein digestion process; thereby causing a build-up of improperly processed amino acids and keto-acids in the body, resulting in systemic dysfunction (1).

The pathophysiology of MSUD revolves around relative deficiency or absolute lack of enzyme that are collectively referred to as branched-chain alpha-ketoacid dehydrogenase complex (or BCKAD). The deficiency is usually a result of an inherited recessive genetic mutation, transmitted by carrier parents. The branched amino acids include leucine, valine and isoleucine and occurs naturally in foods like eggs, red meat and milk.

There are four clinical varieties of MSUD; depending upon the severity, age of onset and enzymatic dysfunction.

  • Classic MSUD: This is the most common as well as severe form of MSUD that is characterized by <2% enzymatic activity of BCKAD. Symptoms are evident in the first few days of post-natal life.
  • Intermediate MSUD: This clinical variety is rather rare and is marked by 3-8% enzymatic activity. The clinical presentation is highly variable.
  • Intermittent MSUD: The clinical severity is mild and in most cases there is no physical or neurological dysfunction. The enzymatic activity is usually 8 -15% and onset is usually delayed until the child is older than 2 years.
  • Thiamine-responsive MSUD: As the name indicates, the clinical response and symptomatology in this clinical variety improves with Thiamine (or B1) supplementation. Symptoms are usually evident during early infancy.

Risk Factors For Maple Syrup Urine DiseaseUrine color image

A positive history of MSUD in the family can greatly aggravate the risk of giving birth to babies with MSUD. The risk of giving birth to another baby with MSUD is 50% if one child is diagnosed with this condition.

Classic Symptoms Of Maple Syrup Urine Disease

As discussed previously, the onset of symptoms vary according to the clinical variety of MSUD. Some common symptoms of classic MSUD are:

  • Extreme fatigue, irritability and lethargy
  • High pitched cry
  • Poor feeding, loss of appetite and weight loss
  • Irregular sleep rhythm
  • Poor suckling
  • Alternating episodes of hypotonia (flaccidity of muscles) and hypertonia (rigidity of muscles)
  • Characteristic maple-scented urine, sweat and earwax

More severe and poorly managed forms of MSUD presents with symptoms of neurological dysfunction and developmental delays; such as:

  • Seizures
  • Poor growth
  • Inadequate weight gain
  • Neurological deficits
  • Feeding problems
  • Ataxia (deficits of muscle coordination)

Management/ Treatment Of Maple Syrup Urine Disease

Early diagnosis and prompt management can minimize the risk of complications. It is imperative to keep in mind that neurological dysfunction and physical impairment is almost always inevitable in poorly managed cases of MSUD. For example, high intake of branched-chain amino-acids can lead to irritability, seizures, lethargy, loss of mental alertness and vomiting. In severe cases, affected person may experience metabolic acidosis, cerebral edema, poor perfusion of brain, coma, blindness, mental retardation or even death.

It is highly recommended to see a doctor for optimal management of MSUD. Experts recommend:

  • Dietary restriction of certain foods that are rich in branched-chain amino acids is an essential first step in the management of MSUD. Study reported in the Orphanet Journal of Rare Diseases (2) suggested that reducing the consumption of dietary proteins from 19% to 6% can improve the concentration of branched-chain amino acids in the brain tissue by 28%.
  • During infancy, the baby is usually fed a diet high in amino acids and sugars via intravenous route (without branched chain amino acids) to promote the endogenous utilization of leucine, valine and isoleucine.
  • The dietary restrictions usually lasts for the lifetime. It is therefore imperative to work closely with a dietitian to minimize the risk of dietary deficiencies of vital proteins, minerals and vitamins.

According to a new study reported in the International Journal of Developmental Neuroscience (1) investigators suggested that supplementation with L-Carnitine can help in reducing the oxidative stress and lipid peroxidation in MSUD patients and thereby helps in reducing the severity of neurological dysfunction.


1. Mescka, C. P., Wayhs, C. A. Y., Vanzin, C. S., Biancini, G. B., Guerreiro, G., Manfredini, V., … & Vargas, C. R. (2013). Protein and lipid damage in maple syrup urine disease patients: l-carnitine effect. International Journal of Developmental Neuroscience, 31(1), 21-24.

2. Vogel, K. R., Arning, E., Wasek, B. L., McPherson, S., Bottiglieri, T., & Gibson, K. M. (2014). Brain–blood amino acid correlates following protein restriction in murine maple syrup urine disease. Orphanet journal of rare diseases, 9(1), 1.

3. Carpenter, K. (2015). Branched Chain Amino Acids and Maple Syrup Urine Disease. In Branched Chain Amino Acids in Clinical Nutrition (pp. 145-156). Springer New York.

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