What is carnosinemia?

Causes and Symptoms
Diagnosis and treatment

Carnosinemia, also known as carnosinase deficiency, is an extremely rare inherited metabolic disorder. It presents with increased 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 impairment, hypotonia, myoclonic seizures, and inability to socialize.

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

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Carnosinaemia was initially characterized as an inherited metabolic disorder 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 impairment and myoclonic seizures. Even after all sources of the dipeptide were removed from the diet, both excreted carnosine in urine.

Perry et al. (1967) hypothesized that one, or possibly both, had a deficiency in carnosinase activity. A child was born to first cousin parents 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 to their constituent amino acids was nearly absent in both patients, according to Perry et al. (1968).

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

Willy et al. (1997) described a 30-month-old child with hypotonia, developmental delay, and tremors who excreted substantial levels of carnosine and anserine while eating only small amounts of meat. These abnormalities were ameliorated but not eliminated by a strict meatless diet. Serum carnosinase activity was found to be extremely low.

Causes and Symptoms

Although the specific nature of the biochemical abnormality that causes carnosinemia is unknown, carnosinase, the enzyme that breaks down carnosine, is present in both the brain and the blood. Studies of muscle tissue from affected individuals reveal that the enzyme carnosinase is aberrant in its metabolism of two dipeptides found in meats, carnosine and anserine.

The CNDP1 (Carnosine Dipeptidase 1) gene encodes carnosinase (CN1), an enzyme that degrades histidine-containing dipeptides such as carnosine, anserine and homocarnosine. Carnosinemia is thought to be passed down in the family in an autosomal recessive fashion. The genetic basis of carnosinemia has not been definitively confirmed to be attributable to CNDP1 mutations, but reduced CN1 function is expected to increase serum carnosine concentrations.

Carnosinaemia and serum carnosinase deficiency have a wide range of clinical manifestations. 80-99% of patients have elevated urine carnosine, loss of developmental milestones and intellectual disability. Extreme drowsiness and seizures are common signs of carnosinemia in children under one year old. Children with this condition have stunted growth, low muscle tone, motor difficulties, and intellectual development delays.

Myoclonic seizures can occur during seizures. Affected children exhibit varying degrees of intellectual deficit in pairs, resulting in intellectual disabilities and developmental regression. Some of the young people affected also have muscle weakness (congenital myopathy). A few patients with few or no symptoms have been diagnosed with this disease.

Carnosineuria (excess carnosine in the urine) and low levels of the enzyme carnosinase in the blood are common in affected individuals. It is also unclear how low levels of carnosinase and/or high levels of carnosine in the body relate to the neurological symptoms of the disorder.


A total of 30 people have been identified worldwide. Both males and females are at risk.

Diagnosis and treatment

Testing for amino acid amounts in blood and/or urine may indicate abnormally high levels of carnosine and anserine in serum and urine, indicating carnosinemia. The carnosinase enzyme in the blood can be detected by highly specialized blood tests. After eliminating meat from the diet, a serum and/or urine amino acid study is used to establish the diagnosis.

Since there is no effective drug treatment for carnosinemia, it is treated symptomatically and supportively. Carnosine, a dipeptide containing histidine and alanine, is abundant in meat. When carnosinase is deficient, carnosine levels increase in blood and urine.

A strict meatless diet may relieve symptoms, but it will not cure the disease. A vegetarian diet lowers serum carnosine levels by reducing the amount of carnosine and anserine supplied to the body. However, it is uncertain whether this has an impact on symptoms or disease progression. Patients with carnosinemia and their families should seek genetic counseling.


Further Reading


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