What is carnosinemia?

Causes and Symptoms
Diagnosis and Treatment

Carnosinemia, also known as carnosinase deficiency, is an extremely rare hereditary metabolic disease. It presents with elevated levels of carnosine in the urine and low levels or absence of carnosinase in the blood. It is associated with severe neurological symptoms in humans and is characterized by developmental delays and seizures. Common symptoms include tremors, psychomotor disturbances, hypotonia, myoclonic seizures, and failure to engage in social relationships.

Carnosine is a dipeptide composed of beta-alanine and histidine found in skeletal muscle cells and cells of the nervous system. As a result of this condition, there is an accumulation of carnosine in the urine, cerebrospinal fluid, blood and nervous tissue.

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Carnosinemia was initially characterized as an inherited metabolic disease in 1967, and was later shown to be caused by a lack of serum carnosinase in 1968. Perry et al. (1967) described two unrelated children who had a developing neurological disorder with severe mental illness. deficiency and myoclonic seizures. Even after all sources of the dipeptide were removed from the diet, both excreted carnosine in the urine.

Perry et al. (1967) speculated that one, or perhaps both, was deficient in carnosinase activity. One child was born to parents of first cousins ​​and had German and Dutch ancestry. The other youngster came from a Chinese family. The enzyme in normal human serum that hydrolyzes the dipeptides carnosine and anserine into their constituent amino acids was almost absent in the two patients, according to Perry et al. (1968).

Terplan and Cares (1972) documented another family with this unusual abnormality. Two brothers, ages seven and four, had died. A 6-year-old sister appeared to be normal, but she was experiencing chemical changes. Carnosinase activity in the parents is low. The older boy’s autopsy revealed extensive axonal degeneration, many gray matter spheroids, demyelination, fibrosis and loss of Purkinje fibers.

Willie et al. (1997) described a 30-month-old child with hypotonia, developmental delay and tremor who secreted significant amounts of carnosine and anserine despite eating only small amounts of meat. These abnormalities were improved but not eliminated by a strict meat-free diet. The activity of serum carnosinase was found to be extremely low.

Causes and Symptoms

While the specific nature of the biochemical anomaly causing carnosinemia is unknown, carnosinase, the enzyme that breaks down carnosine, is present in both the brain and blood. Studies of muscle tissue from affected humans reveal that the enzyme carnosinase is aberrant in the metabolism of two dipeptides found in meat, carnosine and anserine.

The CNDP1 gene (Carnosine Dipeptidase 1) encodes carnosinase (CN1), an enzyme that breaks down histidine-containing dipeptides such as carnosine, anserine, and homocarnosine. Carnosinemia is believed to be passed down through the family in an autosomal recessive manner. It has not been formally confirmed that the genetic basis of carnosinemia can be attributed to CNDP1 mutations, but impaired CN1 function should increase serum carnosine concentrations.

Carnosinemia and serum carnosinase insufficiency have a wide range of clinical manifestations. 80-99% of patients experience high levels of carnosine in the urine, loss of developmental milestones and intellectual disability. Extreme drowsiness and seizures are common symptoms of carnosinemia in children under one year of age. Children with this condition have stunted growth, low muscle tone, motor problems, and intellectual development delays.

Myoclonic seizures can occur with seizures. Affected children show varying degrees of intellectual disability by two, leading to intellectual impairment and developmental decline. Some of the affected young people also have muscle weakness (congenital myopathy). A few patients with little to no symptoms have been diagnosed with this disease.

Carnosineuria (too much carnosine in the urine) and low levels of the enzyme carnosinase in the blood are common in affected individuals. It is also not known how low carnosinase and/or high carnosine levels in the body are related to the neurological symptoms of the condition.


A total of 30 people have been identified worldwide. Both men and women are at risk.

Diagnosis and Treatment

Testing the levels of amino acids in the blood and/or urine may indicate abnormally high levels of carnosine and anserine in the serum and urine, suggestive of carnosinemia. The enzyme carnosinase in the blood can be detected through highly specialized blood tests. After meat has been eliminated from the diet, an amino acid test of serum and/or urine is used to make the diagnosis.

Because there is no effective drug treatment for carnosinemia, it is treated symptomatically and supportively. Carnosine, a dipeptide containing histidine and alanine, is commonly found in meat. When carnosinase is deficient, carnosine levels in the blood and urine rise.

A strict meat-free diet can help with symptoms, but it does not cure the disease. A vegetarian diet lowers serum carnosine levels by reducing the amount of carnosine and anserine delivered to the body. However, it is uncertain whether this will have any impact on symptoms or disease progression. Patients with carnosinemia and their families should seek genetic counseling.


Further Reading


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