An inherited metabolic disorder characterized by severe mental defect and myoclonic seizures. The clinical features include a variety of neurological symptoms such as hypotonia, developmental delay, mental retardation, sensory neuropathy, tremors, and demyelinization of gray matter.
Serum Carnosinase Deficiency; Beta-Alanine-Pyruvate Aminotransferase; Hyper-Beta Carnosinemia.
Unknown, less than 10 cases have been described.
Autosomal recessive transmission with the mutation located on 18q21.3. Parental consanguinity has been described in some of the cases.
This medical condition exists in two forms:
Type I: Cellular/tissue carnosinase: where the enzyme is found in every tissue in the body. Carnosinase hydrolyses both carnosine and anserine. Tissue carnosinase is identified as a ‘nonspecific dipeptidase’ with the ability to hydrolyze a range of dipeptide substrates, including prolinase (an enzyme necessary in the hydrolyzation of hydrophobic dipeptides).
Type II: Serum carnosinase: which is diagnosed by the presence of carnosinase in the plasma. The presence of carnosinuria is the usual metabolic indicator of systemic carnosinase deficiency. This form of the dipeptidase is usually found in the plasma after late infancy or early childhood and slowly progresses to adult levels by age 15. Unlike tissue carnosinase, serum carnosinase also hydrolyzes the GABA metabolite homocarnosine. Homocarnosinosis, a severe neurological disorder, is caused by the presence of an excessive amount of homocarnosine in the brain.
Peri- and initial postnatal development may appear normal, but then at the age of 4 to 5 months, the disorder may manifest with myoclonic seizures and loss of already acquired milestones. By the age of 2 years, one of the patients was profoundly mentally delayed and suffered from spastic athetoid quadriparesis. At the age of 3 to 4 years, he had tonic-clonic seizures, optic atrophy, and suprabulbar signs. This progressive neurologic disorder with variable phenotype is associated with severe mental retardation, myoclonic seizures, tremor, sensory peripheral neuropathy, and hypotonia caused by a carnosinase deficiency. Central nervous system findings at autopsy may include severe axonal degeneration, loss of Purkinje fibers, and neuraxonal spheroids in the gray matter as a result of demyelinization and reactive fibrosis. Carnosine, a dipeptide of histidine and alanine, is found in significant concentrations in meat. Carnosinase deficiency results in high levels of carnosine in serum and urine. A strictly meat-free diet can result in amelioration of the symptoms, but does not provide a cure.
Precautions before anesthesia
Anticonvulsant therapy should be continued until the morning of surgery and resumed as soon as possible postoperatively and given intravenously if oral intake is not possible. Developmental delay may cause agitation and stress in the perioperative period, thus anxiolytic and sedative premedication and/or presence of a parent (or ...