image by: Mara Rae Carmichael

HWN Suggests

When It Doesn’t Smell Like Rotavirus; Maple Syrup Urine Disease in the 21St Century

Expanded newborn screens (NBS) have had a dramatic impact on early diagnosis and treatment of inborn errors of metabolism (IEM) such as classic MSUD. However, IEM variants may be missed on the NBS. When minor illnesses in these patients lead to metabolic crises, the diagnosis may only be made if the provider has a high index of suspicion. MSUD results from decreased branched chain ketoacid dehydrogenase (BCKD) complex activity with subsequent elevation of leucine, isoleucine and valine, and their corresponding ketoacids. Leucine is neurotoxic and causes cerebral edema. Ketoacids result in the maple syrup smell. Variants of MSUD reflect the spectrum of dysfunction on BCKD complex activity.

read full article

Featured

 Maple Syrup Urine Disease (MSUD)

Maple syrup urine disease (MSUD), also called branched-chain aminoaciduria, is so called because the urine of affected individuals smells like maple syrup or burnt sugar. The cause of the odor in the urine of MSUD patients is a catabolic metabolite of leucine identified as sotolone [3-hydroxy-4,5-dimethyl-2(5H)-furanone]. This compound is also found in the seeds of the herb, fenugreek (Trigonella foenum-graecum) which are used as a spice.

 Maple Syrup Urine Disease: The Rare Disease I Guarantee You've Never Heard Of

However, considering that it is extremely rare, I can't say that I blame anyone for not being educated on the topic. And that's why I'm here, to educate. MSUD is diagnosed with a blood test during newborn screening. For some subtypes, such as intermittent and intermediate, it isn’t diagnosed until the child is a bit older and starts showing symptoms. Then, doctors may check amino acid levels in the blood and urine.

Articles of Interest

About Maple Syrup Urine Disease (MSUD)

The first clinical description of Maple Syrup Urine Disease (MSUD) was published in 1954 by Dr. Bickel, along with his colleagues. They identified the disorder in a newborn who exhibited the characteristic "maple syrup" odour in their urine. This odour was later determined to be a result of the accumulation of branched-chain amino acids (BCAAs) in the bloodstream, a hallmark of the disorder.

Life with Maple syrup

I am 6 years old and was diagnosed with Maple syrup urine disease (MSUD for short) through the newborn screening. It’s a metabolic disorder that affects 1 in 185,000 newborns. My body can’t break down 3 amino acids… which leads to build up of toxic substances and can cause organ and brain damage and even go into coma. I’m on a strict low protein diet and need to weigh everything I consume to avoid metabolic decompensation. I also have to drink a medical formula for the rest of my life with all I need to live healthy! Overall if under control I’m a happy boy living a normal life

Ava’s doctors hadn’t heard of maple syrup urine disease – but a new helpline for rare conditions could help those like her

This article is more than 2 years old Ava’s doctors hadn’t heard of maple syrup urine disease – but a new helpline for rare conditions could help those like her This article is more than 2 years old Australians with rare and complex conditions hope new federally funded program will help them access better support and services Follow our Australia news live blog for latest updates Get our morning and afternoon news emails, free app or daily news podcast Natasha May Natasha May Sun 17 Dec 2023 09.00 EST Share 1 When Tammie Rees tells people her daughter Ava has maple syrup urine disease, most people, not even medical professionals, have heard of it before. The rare metabolic disorder is caused by a defect in the enzymes that break down amino acids which come from protein. Without treatment, the urine smells very sweet, like maple syrup. If the harmful build-up of the amino acids build up in the blood, it can cause brain damage.

Brain Branched-Chain Amino Acids in Maple Syrup Urine Disease: Implications for Neurological Disorders

Maple syrup urine disease (MSUD) is an autosomal recessive disorder caused by decreased activity of the branched-chain α-ketoacid dehydrogenase complex (BCKDC), which catalyzes the irreversible catabolism of branched-chain amino acids (BCAAs). Current management of this BCAA dyshomeostasis consists of dietary restriction of BCAAs and liver transplantation, which aims to partially restore functional BCKDC activity in the periphery.

Experimental Breakthrough

In 1954, John Menkes et al. published the first article describing the syndrome that would become known as Maple Syrup Urine Disease. The article, entitled “A New Syndrome: Progressive Infantile Cerebral Dysfunction Associated with an Unusual Urinary Substance” and published in Pediatrics, focused on four specific cases of MSUD. Much of the paper describes the results of clinical tests that were performed on each patient along with patient histories and treatment regiments. In two cases, autopsy results were also reported.

Gene therapy shows promise in treating maple syrup urine disease

A gene replacement therapy was able to restore metabolic homeostasis and prevent perinatal death in mouse and calf models of maple syrup urine disease (MSUD), a rare disease in which the body is unable to process amino acids properly.

His Sister Died 12 Days After Suffering Mysterious Spells. Now He Had Them

The patient had a rare form of a rare disorder called maple syrup urine disease (M.S.U.D.). Patients with M.S.U.D. are born with abnormalities in the machinery used to break down certain amino acids, the building blocks of proteins. This causes the accumulation of unmetabolized protein components, which can damage the body. Untreated, the disease can result in significant, often fatal swelling of the brain. The name comes from the smell of maple syrup in urine and sweat sometimes caused by the buildup of amino acids during episodes of protein overload. The patient never experienced this.

Managing a rare condition with a sweet scent

MSUD is an inherited metabolic disorder in which enzymes responsible for breaking down certain amino acids fail to function properly. Without treatment, the resulting buildup of amino acids, especially leucine, in the blood can cause brain swelling, seizures and intellectual disabilities. In severe cases, infants may not survive beyond the first few weeks of life.

Maple Syrup Urine Disease (Branched-Chain Ketoaciduria)

Maple syrup urine disease (MSUD) or branched-chain ketoaciduria is caused by a deficiency in activity of the branched-chain α-keto acid dehydrogenase (BCKD) complex. This metabolic block results in the accumulation of the branched-chain amino acids (BCAAs) leucine, isoleucine, and valine, and the corresponding branched-chain α-keto acids (BCKAs). Based on the clinical presentation and biochemical responses to thiamine administration, MSUD patients can be divided into five phenotypes: classic, intermediate, intermittent, thiamine-responsive, and dihydrolipoyl dehydrogenase (E3)-deficient. Classic MSUD has a neonatal onset of encephalopathy

Maple Syrup Urine Disease Developed by Angela Messer ...

Maple Syrup Urine Disease is a rare condition, affecting around 1 per every 185, 000 infants. MSUD is one of the inborn errors of metabolism, resulting from genetic variants in the DNA encoding the enzyme complex that breaks down branched chain amino acids (leucine, valine, and isoleucine). MSUD manifests as inability to properly breakdown and metabolize BCAAs...

Maple syrup urine disease: mechanisms and management

The classic presentation occurs in the neonatal period with developmental delay, failure to thrive, feeding difficulties, and maple syrup odor in the cerumen and urine, and can lead to irreversible neurological complications, including stereotypical movements, metabolic decompensation, and death if left untreated. Treatment consists of dietary restriction of BCAAs and close metabolic monitoring. Clinical outcomes are generally good in patients where treatment is initiated early. Newborn screening for MSUD is now commonplace in the United States and is included on the Recommended Uniform Screening Panel (RUSP). We review this disorder including its presentation, screening and clinical diagnosis, treatment, and other relevant aspects pertaining to the care of patients.

Maple syrup urine disease: mechanisms and management

The classic presentation occurs in the neonatal period with developmental delay, failure to thrive, feeding difficulties, and maple syrup odor in the cerumen and urine, and can lead to irreversible neurological complications, including stereotypical movements, metabolic decompensation, and death if left untreated.

Metabolic Crisis - The ED Doc’s Approach

When I think of inborn errors of metabolism, I immediately begin to hyperventilate and feel as though I am back in the library in medical school frantically trying to study for Step 1. But then I remember: “I’m an emergency medicine doctor, and it’s less important that I remember that the enzyme branched-chain alpha blah blah blah is deficient in the autosomal something maple syrup urine disease, and more important that I remember how to recognize and subsequently stabilize these patients when they come into my department in metabolic crisis.” And even luckier for me, it’s actually pretty straightforward so long as you know what labs to order and how to respond to them.

Resources

9 Weird Human Body Smells and What They Mean

A syrup-sweet urine smell is the hallmark of maple syrup urine disease. Pediatric screening programs flag that odor as a warning sign shortly after birth.

MSUD Family Support Group

The MSUD Family Support Group is a non-profit, mostly volunteer-run organization serving families and professionals worldwide. Founded in 1982 when a group of families gathered together for mutual support and shared information, our organization continues to grow and develop resources to meet our goals...

Florida Newborn Screening

Maple syrup urine disease (MSUD) is a condition in which the body is unable to break down certain proteins. The condition is named for the sweet odor of the urine of untreated babies. Individuals with MSUD have trouble breaking down certain amino acids, the building blocks of proteins. Early detection and treatment can often prevent many of the serious outcomes of MSUD. Forms of MSUD vary widely in the severity of signs. “Classic MSUD” is the most common form and is seen in babies. Babies with classic MSUD usually begin showing signs shortly after birth. These signs include poor appetite, trouble sucking during feeding, weight loss, high pitched cry, urine that smells sweet like maple syrup or burnt sugar, sleeping longer or more often, tiredness, irritability, vomiting, and developmental delays.

Metabolic Support UK

Everyone has a pair of genes that make the branched chain ketoacid dehydrogenase enzyme. In children with MSUD, neither of these genes works correctly. These children inherit one non-working MSUD gene from each parent. Parents of children with MSUD are carriers of the condition. Carriers do not have MSUD because the other gene of this pair is working correctly

E.S.PKU Metabolic Passport

Maple syrup urine disease (MSUD for short) is a rare inherited metabolic disease. This is a condition that affects the body's ability to break down branched chain amino acids, particularly leucine such as leucine, isoleucine and valine. If left untreated these amino acids accumulate which may result in irreversible neurological impairment and death. Treatment involves maintaining an appropriate low-protein diet and monitoring the level of amino acids in the blood.

NORD

Maple syrup urine disease (MSUD) is a rare genetic disorder characterized by deficiency of an enzyme complex (branched-chain alpha-keto acid dehydrogenase) that is required to break down (metabolize) the three branched-chain amino acids (BCAAs) leucine, isoleucine and valine, in the body. The result of this metabolic failure is that all three BCAAs, along with a number of their toxic byproducts, (specifically their respective organic acids), all accumulate abnormally. In the classic, severe form of MSUD, plasma concentrations of the BCAAs begin to rise within a few hours of birth. If untreated, symptoms begin to emerge, often within the first 24-48 hours of life.

StatPearls

Maple Syrup Urine Disease (MSUD) is a rare genetic disorder impacting branched-chain amino acid metabolism. This mutation is tested for perinatally, but a high suspicion must be present given this entity's significant and potentially irreversible developmental effects. Causes of mortality include cerebral edema, seizures, coma, respiratory failure, and metabolic derangements.