Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serum carnosinase deficiency (McKusick 21220) is a rare condition, described in 13 cases. Ten additional individuals with serum carnosinase deficiency have been identified. All continued to excrete increased amounts of carnosine in their urine despite a meat-free diet for 3 days. Serum carnosinase activity ranged from 0-30% of normal. In four individuals a normal Km for carnosine of 0.12 mM was observed, while in five individuals an increased Km was found. Homocarnosine levels in CSF in three individuals ranged from 3.4 to 15 mM. Clinical symptoms in these individuals were as follows: attention deficit disorder: 4; non progressive developmental delay: 1; neurofibromatosis: 1; absences seizures: 1; severe, but non-progressive mental retardation, seizures and neurosensory hearing loss: 1; progressive childhood dementia; 1; clinically normal: 1. There was no correlation between severity and type of the neurological symptoms and residual serum carnosinase activity. Although a definite conclusion can only be made after a considerably higher number of individuals has been analyzed, the suspicion that serum carnosinase deficiency is unrelated to the neurological symptoms is strengthened by these observations. There may, however, be an association with a predisposition for mental deficiency.
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PMID:Serum carnosinase deficiency: a non-disabling phenotype? 409 64

Gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the mammalian central nervous system, is produced from glutamic acid in a reaction catalysed by glutamic acid decarboxylase. The sequential actions of GABA-transaminase (converting GABA to succinic semialdehyde) and succinic semialdehyde dehydrogenase (oxidizing succinic semialdehyde to succinic acid) allow oxidative metabolism of GABA through the tricarboxylic acid cycle. The inherited disorders of GABA metabolism include: (1) pyridoxine-dependent seizures (?glutamic acid decarboxylase deficiency) (> 50 patients); (2) GABA-transaminase deficiency (2 patients/1 family); (3) succinic semialdehyde dehydrogenase deficiency (32 patients/21 families); and (4) homocarnosinosis associated with serum carnosinase deficiency (3 patients/1 family). Homocarnosine is a brain-specific dipeptide of GABA and L-histidine. Of these four defects, definitive enzymatic diagnoses have been made only for GABA-transaminase and succinic semialdehyde dehydrogenase deficiencies. The presumptive mode of inheritance for all disorders is autosomal recessive, and all are associated with central nervous system dysfunction. Only succinic semialdehyde dehydrogenase deficiency manifests organic aciduria, which may account for the higher number of patients identified with this disorder; identification of additional patients with some of the other disorders will require increased request for analysis of cerebrospinal fluid metabolites by paediatricians and neurometabolic specialists.
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PMID:Inherited disorders of GABA metabolism. 841 16

The dipeptides carnosine and anserine, found exclusively in meats, are hydrolyzed in serum by the enzyme carnosinase. Several reports of serum carnosinase deficiency describe a variable phenotype, which ranges from normal to severe psychomotor retardation, hypotonia, and myoclonic seizures in the first year of life. We report the case of a 30-mo-old girl with hypotonia, developmental delays, and tremor. Although consuming nominal quantities of meal, she excreted large amounts of carnosine and anserine. A strict meat-free diet ameliorated, but did not eliminate, these abnormalities. Serum carnosinase activity was found to be extremely low. Analysis of this child's chromosomes revealed a terminal deletion of chromosome 18 with breakpoint at q21.3. Neither parent exhibited this deletion, suggesting it was generated de novo in the patient or in a parental germ cell. Molecular studies showed that the patient's paternal chromosome 18 was deleted. Urinary carnosine excretion and serum carnosinase activity were normal in the patient's father. The mother had low carnosinase activity. The patient's brother exhibited moderate hypercarnosinuria and intermediate enzyme activity, consistent with the carrier state for carnosinase deficiency. Cumulatively, these findings suggest that the locus for this enzyme resides on the distal long arm of chromosome 18, and they are consistent with an unusual mechanism for the inheritance of this, typically autosomal recessive, condition. We conclude that this patient is likely hemizygous for the defect, having received the deficiency allele from her mother and, by virtue of the chromosomal deletion, no allele from her father. This represents the first report of a chromosomal abnormality in association with serum carnosinase deficiency and should aid in further localization of the gene encoding serum carnosinase.
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PMID:A deletion in the long arm of chromosome 18 in a child with serum carnosinase deficiency. 902 40