About branched chain ketonuria i

What is branched chain ketonuria i?

Maple syrup urine disease (MSUD) is a rare genetic disorder characterized by deficiency of certain enzymes (branched-chain alpha-keto acid dehydrogenase complex) required to breakdown (metabolize) specific amino acids in the body. Because these amino acids are not metabolized, they, along with their various byproducts, abnormally accumulate in the cells and fluids of the body. Such accumulation can cause a variety of symptoms including lethargy, irritability, poor feeding, abnormal movements and a characteristic odor of maple syrup in the earwax (cerumen), sweat and urine of affected individuals. In addition, if untreated various neurological complications including seizures, coma and brain damage may occur. Failure to promptly detect and treat MSUD can lead to life-threatening complications. However, the disorder can be successfully managed through a specialized diet. Even with treatment affected individuals remain at risk for developing episodes of acute illness (metabolic crisis) often triggered by infection, injury, failure to eat (fasting) or psychological stress. During these episodes there is a rapid, sudden spike in amino acid levels necessitating immediate medical intervention.

At least four subtypes of MSUD have been identified in the medical literature. Some researchers include a fifth subtype, although other researchers consider this a separate distinct disorder. The various subtypes of MSUD have different levels of residual enzyme activity, different severity, and different ages of onset. All forms are inherited as autosomal recessive traits.

What are the symptoms for branched chain ketonuria i?

Ketonuria may be a sign that you have ketoacidosis or leading to it. The higher your levels of ketones, the more severe the symptoms and the more dangerous it can become. Depending on severity, signs and symptoms can include:

  • thirst
  • fruity smelling breath
  • dry mouth
  • fatigue
  • Nausea or vomiting
  • frequent urination
  • Confusion or difficulty focusing

Your doctor may find related signs of ketonuria:

  • high blood sugar
  • significant dehydration
  • electrolyte imbalance

Additionally, there may be signs of illnesses such as sepsis, pneumonia, and urinary tract infections that can lead to high ketone levels.

What are the causes for branched chain ketonuria i?

Ketogenic diet

Ketonuria is a sign that your body is primarily using fats and protein for fuel. This is called ketosis. It’s a normal process if you’re fasting or on a low-carbohydrate, ketogenic diet. A ketogenic diet does not typically pose a health risk if it’s done in a balanced way.

Low insulin levels

Most of the energy your body uses comes from sugar or glucose. This is normally from the carbohydrates you eat or from stored sugars. Insulin is a vital hormone that transports sugar into every cell, including your muscles, heart, and brain.

People with diabetes may not have enough insulin or be able to use it properly. Without insulin, your body can’t efficiently move sugar into your cells or store it as fuel. It must find another power source. Body fats and proteins are broken down for energy, producing ketones as a waste product.

When too many ketones pile up in your bloodstream, a condition called ketoacidosis or diabetic ketoacidosis can occur. This is a life-threatening condition that makes your blood acidic and can harm your organs.

Ketonuria usually happens along with ketoacidosis. As ketone levels rise in your blood, your kidneys try to get rid of them through urine.

If you have diabetes and have developed ketonuria, you likely also have high blood sugar levels, or hyperglycemia. Without enough insulin, your body can’t properly absorb sugar from digested food.

Other causes

You can develop ketonuria even if you don’t have diabetes or are on a strict ketogenic diet. Other causes include:

  • drinking excess alcohol
  • excessive vomiting
  • pregnancy
  • starvation
  • illness or infection
  • heart attack
  • emotional or physical trauma
  • medications, such as corticosteroids and diuretics
  • drug use

What are the treatments for branched chain ketonuria i?

If your ketonuria is due to temporary fasting or changes in your diet, it will likely resolve on its own. You won’t need treatment. Test your ketone levels and your blood sugar and see your doctor for follow-up appointments to make sure.

In more serious situations, ketonuria treatment is similar to treatment for diabetic ketoacidosis. You may require lifesaving treatment with:

  • fast-acting insulin
  • IV fluids
  • electrolytes such as sodium, potassium, and chloride

If your ketonuria is due to illness, you may need additional treatment such as:

  • antibiotics
  • antivirals
  • heart procedures

What are the risk factors for branched chain ketonuria i?

Branched-chain ketonuria, also known as maple syrup urine disorder, is a metabolic disorder caused by the abnormal activity of the Branched-Chain alpha-Keto Acid Dehydrogenase (BCKAD) complex. The enzyme is responsible for the metabolism of branched-chain amino acids. The deficiency of the enzymes leads to the accumulation of the substrate in plasma and urine. The high levels of keto acids lead to serious neurological manifestations that lead to symptoms, such as seizures, lethargy, erratic behavior, spasticity, irritability, and hallucinations.

Risk factors
There are two risk factors for the disease: genetic predisposition and dietary factors.

1. Genetic predisposition: BCK is a genetic disorder that is inherited in an autosomal recessive fashion. Parents who are carriers and affected are the risk factors for a child to inherit the defective gene.
When the parents are asymptomatic carriers, a child born to them has a probability of 0.5 to inherit the disease, whereas a child is bound to be affected when born to affected parents.

2. Dietary factor: Diets containing branched-chain amino acids pose the risk of elevating the clinical manifestations. Food ingredients such as whey, milk, soy protein, beef, chicken, fish, eggs, baked beans, brown rice, almonds, and cashews.

3. Genetic counseling is highly recommended when parents see signs such as an odor of maple syrup in urine when they are stressed. It helps to prevent inheritance.

Symptoms
Early onset: poor feeding, either bottle or breast,lethargy, irritability, neurological signs including athetoid, hypertonia, opisthotonos, and spasticity.
Later onset: erratic behavior, hallucination, loss of appetite, weight loss, anemia, diarrhea, vomiting, seizures, dehydration, and lethargy.
Conditions
Early onset: poor feeding, either bottle or breast, lethargy, irritability, neurological signs including athetoid, hypertonia, opisthotonos, and spasticity.
Later onset: erratic behaviour, hallucination, loss of appetite, weight loss, anaemia, diarrhoea, vomiting, seizures, dehydration, and lethargy.
Drugs
Sodium phenylbutyrate for niytrogen scavenging

Is there a cure/medications for branched chain ketonuria i?

An enzyme complex (branched-chain alpha-keto ketonuria dehydrogenase) is necessary for the body to break down (metabolize) the three branched-chain amino acids (BCAAs) leucine, isoleucine, and valine is lacking in maple syrup urine disease (MSUD), a rare hereditary illness. All three BCAAs, as well as a number of their hazardous byproducts (particularly their respective organic acids), accumulate abnormally as a result of this metabolic failure.

1. To ascertain whether a patient is thiamine-responsive, some doctors advise a trial of thiamine therapy. However, no patient with Branched-chain ketonuria has ever only received thiamine treatment.

2. Even if affected people completely adhere to the prescribed diet, there is always a chance of a metabolic crisis. Instances of metabolic crisis necessitate prompt medical attention to reduce blood levels of branched-chain amino acids, particularly leucine.

3. Several methods, such as dialysis or a procedure where blood is drawn from the body and then passed through a filter before returning to the body, have been used to lower plasma leucine levels (hemofiltration).

4. Aggressive treatment for metabolic crises aims to decrease and then reverse the elevated protein catabolism that underlies these episodes. Because of this, it may be beneficial to increase calories or decrease protein catabolism. This entails consuming a lot of glucose and, if necessary, supplementing it with insulin via a "glucose-insulin drip," as insulin is known to promote endogenous protein synthesis. Another significant calorie source is intravenous fat.

Symptoms
Early onset: poor feeding, either bottle or breast,lethargy, irritability, neurological signs including athetoid, hypertonia, opisthotonos, and spasticity.
Later onset: erratic behavior, hallucination, loss of appetite, weight loss, anemia, diarrhea, vomiting, seizures, dehydration, and lethargy.
Conditions
Early onset: poor feeding, either bottle or breast, lethargy, irritability, neurological signs including athetoid, hypertonia, opisthotonos, and spasticity.
Later onset: erratic behavior, hallucination, loss of appetite, weight loss, anemia, diarrhea, vomiting, seizures, dehydration, and lethargy.
Drugs
Sodium phenylbutyrate for nitrogen scavenging

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