Maple Syrup Urine Disease (Maple Diabetes, MSUD,)

Maple Syrup Urine Disease
Body Parts: Whole Body
Medical Subjects: Children's Health Genetic disease

What Is Maple Syrup Urine Disease?

What is Maple Syrup Urine Disease?

Maple diabetes is a disease caused by the defects of metabolic enzymes in the body, which leads to the degradation and metabolism problems of branched-chain amino acids (mainly including leucine, isoleucine amino acid and valine, which cannot be produced by the human body but are obtained from food), and the accumulation of branched-chain amino acids and their metabolic intermediates (three keto acids).

These three keto acids are excreted from patients' urine, making urine have sweet caramel odor, like the odor of maple syrup, so it is called Maple Syrup Urine Disease, also known as maple diabetes.

These three keto acids can cause damage to the patient's nervous system, leading to damage to the central nervous system (such as increased muscle tension, convulsions, lethargy and coma), difficulty in feeding in infancy and metabolic acidosis. If not treated promptly, correctly and effectively, the patient often dies in infancy.

Maple diabetes is a genetic disease, and consanguinity increases the risk of disease in later generations.

Is maple diabetes common?

In general, maple diabetes is uncommon. Globally, the incidence of maple diabetes is 1 case per 185,000 live births, and Portugal has one of the highest rates of maple diabetes in the world, with 1 case per 88,800 live births.

The disease has a higher incidence in regions or countries with high rates of consanguinity, such as Menopause in Pennsylvania, where the incidence is as high as 1 in 200 live births.

What are the types of maple diabetes?

According to the deficiency of metabolic enzymes and the difference in manifestations, maple diabetes is divided into five types: typical type, E3 deficiency type, thiamine reaction type, intermittent type and mild type.

The first 2 types usually develop in the neonatal period and the latter 3 types can develop in infancy or at any time during childhood. Typical type was the most common, accounting for 3/4.


What Is The Cause Of Maple Syrup Urine Disease?

What causes maple diabetes?

Maple diabetes is a genetic disease caused by genetic problems, is an autosomal recessive genetic disease. Consanguinity greatly increases the risk of disease in later generations.

Who is the main source of maple diabetes?

Mennonites and Amish are susceptible to the disease. The incidence of this disease is higher in regions and countries with high rates of consanguinity.

Can maple diabetes infect?

Maple diabetes is a congenital genetic disease and is not contagious.

Can maple diabetes be inherited?

Maple diabetes will be inherited, following the rules of autosomal recessive inheritance. It can be simply understood that if both husband and wife have no disease manifestation but both carry the disease-causing gene, the offspring will have a 25% chance of getting sick.

In consanguinity, both husband and wife have high genetic similarity and are more likely to carry disease-causing genes at the same time, leading to diseases in later generations.


What Is The Symptoms Of Maple Syrup Urine Disease?

What are the common manifestations of maple diabetes?

  • Typical Maple Diabetes: It is the most common and serious type of maple diabetes, and even if it survives treatment, it can have sequelae of mental retardation and nerve damage. Newborns can show irritability, feeding difficulty, vomiting, limb stiffness, lethargy and other abnormalities within 48 hours after birth, and can develop lethargy and irritability alternately, limb stiffness, apnea, epileptic seizures and cerebral edema signs four days after birth. Symptoms in a breastfed newborn may appear later and can be delayed until 2 weeks after birth. Children often die within weeks or months if they are not correctly diagnosed and treated.

  • Intermittent maple diabetes: patients with this type of metabolic enzyme defects is not serious, so the attack is intermittent, often due to surgery, infection, intake of high protein diet and frequent vomiting and other special circumstances induced attack. The symptoms of the attack are similar to those of the classic type, but the symptoms are milder, and some patients may die during the attack.

  • Mild maple diabetes: maple syrup and mild symptoms in urine during the neonatal period, and maple diabetes later induced when suffering from other diseases, showing the same as the typical type but milder, with effective vitamin B1 treatment.

  • Thiamine-reactive maple diabetes: Thiamine, also known as vitamin B1, is a coenzyme in the metabolism of branched-chain amino acids. This form of expression is also milder and is therapeutically effective with vitamin B1.

  • E3-deficient maple diabetes mellitus: This type of diabetes mellitus has severe manifestations because of the defects in a variety of metabolic enzymes.

What are the serious consequences of Maple diabetes?

Severe maple patients with diabetes, if not through active and effective treatment, acute phase may die because of metabolic poisoning, long-term not active treatment, may appear mental retardation, nervous system damage sequelae.


How To Check Maple Syrup Urine Disease?

How to diagnose maple diabetes?

When doctors diagnose maple diabetes, the main reference is the analysis of amino acids and organic acids.

  • The detection of L- allo-amino acid in her blood is characteristic of this disease.
  • Patients with this disease can detect increased levels of branched-chain amino acids and branched-chain organic acids in bleeding.
  • During the onset of this disease, the concentration of α -ketoisovaleric acid in the blood and the concentration of α-hydroxyisovaleric acid in the urine are increased.

The above tests can confirm the diagnosis.

What tests are done to determine if you have diabetes?

  • Neonatal screening: High suspicion of maple syrup in neonatal urine, sweat, or unexplained metabolic acidosis is required. It can be screened by tandem mass spectrometry, but may not detect patients with milder conditions. For neonates with a family history of maple diabetes, DNA analysis can be performed, or blood samples taken at 18–24 hours after birth for amino acid analysis.

  • Blood glucose and blood gas analysis: understanding the presence of hypoglycemia and metabolic acidosis can help diagnose the disease.

  • Determination of branched chain amino acids and their metabolites: the disease can be confirmed. The specimen may be blood, urine.

  • DNA analysis: used to confirm diagnosis and predict therapeutic reactivity.

Which diseases are easy to confuse with Maple diabetes? How to distinguish?

Maple diabetes may be confused with other brain disorders because of common manifestations of nervous system damage. Doctors need to tell the difference by doing a laboratory test. Identification is primarily by detection of branched-chain amino acids and their metabolites.


How To Prevent Maple Syrup Urine Disease?

Avoid consanguinity. If there is a family history of maple diabetes or a risk factor, prenatal diagnosis can be made by measuring amniotic fluid or villous cell enzyme activity, and the pregnancy can be selectively terminated to avoid the birth of a diseased fetus.


How To Treat Maple Syrup Urine Disease?

Which department should patients with maple diabetes go to?

Department of pediatrics and endocrinology.

Can maple diabetes heal itself?

Maple diabetes does not heal itself, and if it is not treated promptly and effectively, mental retardation, sequelae of nervous system damage, and even death will appear.

How to treat maple diabetes?

The treatments of maple diabetes mainly include diet therapy, acute metabolic crisis, medication and surgery.

  • Dietary treatment: Start early and stick to it for the rest of your life. Normal development is expected if dietary therapy is initiated within 1 week of birth or prior to severe neurological impairment. The intake of branched-chain amino acids in foods must be limited, and the therapeutic goal is to maintain the concentration of branched-chain amino acids in blood within the normal range. Formulated foods or medical foods may be used. Weekly blood amino acid analysis is required for food modification at the beginning of treatment.
  • Treatment of acute metabolic crisis: Acute metabolic disorder of maple diabetes results in the accumulation of a large number of branched-chain amino acids and their metabolic intermediates in the blood, leading to severe acidosis and rapid decline in nervous system function, which needs active treatment. Such as dialysis, standard total intravenous nutrition with branched-chain amino acids removed, treatment with glucose plus small doses of insulin, and gene recombinant growth hormone.
  • Drug therapy: For patients with effective thiamine therapy, vitamin B1 can be given 10–1000 mg per day.
  • Surgical treatment: For children with typical type of maple diabetes, liver transplantation can be considered once the diagnosis is confirmed, and the results show that the biochemical metabolism returns to normal soon after the operation.

Can maple diabetes be cured completely?

The disease cannot be radically treated, but timely and correct treatment can enable the child to survive and the symptoms can be improved.


What Should Patients With Maple Syrup Urine Disease Pay Attention To In Life?

What should patients with Maple Syrup Urine Disease pay attention to in diet?

The diet must limit the intake of branched-chain amino acids in food, but it cannot be excessively limited, and the diet needs to be adjusted according to the results of blood amino acid analysis.

If the branched-chain amino acids are excessively restricted (for example, leucine and isoleucine amino acids are excessively restricted), skin damage such as perioral papillary erythema, diaper dermatitis, and the like may occur.

Do Maple diabetic patients need to be reviewed? How to review?

Maple patients with diabetes need regular follow-up.

  • For patients who develop the disease in infancy, it is recommended that monitoring be performed weekly for children younger than 3 months of age, biweekly to monthly for children 3 to 12 months of age, and monthly thereafter. The content of measurement was plasma amino acid concentration, and the intake of branched-chain amino acids was adjusted according to the results of measurement.
  • For patients who develop disease after infancy, it is recommended that plasma amino acid concentrations be monitored monthly until they stabilize and every 3–6 months thereafter.

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