Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The adult type of neuronal ceroid lipofuscinosis (NCL) occurred in a 49-year-old man and his 51-year-old sister. They showed episodic stuporous and psychotic states, mental retardation, generalized convulsions, and ichthyosis vulgaris. At autopsy the woman had excessive accumulation of lipofuscin throughout the CNS. The degree of neuronal lipopigment accumulation was very severe in the neurons of the thalamus, substantia nigra, inferior olivary nuclei, motor nuclei of the brain stem, and cerebral cortex. Mental symptoms, such as stupor, excitement, hallucinations, and delusions, were the predominant clinical manifestations and so were misdiagnosed as schizophrenia. Though the clinical diagnosis of the adult type of NCL (Kufs' disease) is difficult because of its wide variety of manifestations, symptoms such as episodic psychotic and stuporous states accompanied by convulsive disorders with mild neurologic signs may be an indication of this disease.
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PMID:Familial occurrence of adult-type neuronal ceroid lipofuscinosis. 647 18

The neuronal ceroid lipofuscinoses (NCLs) are clinically and genetically heterogeneous neurodegenerative disorders. Most are autosomal recessively inherited. Clinical features include a variable age of onset, motor and mental decline, epilepsy, visual loss, and premature death. Mutations in eight genes (PPT1/CLN1, TPP1/CLN2, CLN3, CLN5, CLN6, MFSD8/CLN7, CLN8) have been identified and several more are predicted to exist, including two provisionally named CLN4 and CLN9. Despite excessive in vitro and in vivo studies, the precise functions of the NCL proteins and the disease mechanisms remain elusive. To date 365 NCL-causing mutations are known, with 91 novel disease-causing mutations reported. These are reviewed with an emphasis on their complex correlation to phenotypes. Different mutations within the NCL spectrum can cause variable disease severity. The NCLs exemplify both phenotypic convergence or mimicry and phenotypic divergence. For example, mutations in CLN5, CLN6, MFSD8, or CLN8 can underlie the clinically similar late infantile variant NCL disease. Phenotypic divergence is exemplified by different CLN8 mutations giving rise to two very different diseases, the mild CLN8 disease, EPMR (progressive epilepsy with mental retardation), and the more severe CLN8 disease, late infantile variant. The increase in the genetic understanding of the NCLs has led to improved diagnostic approaches, and the recent proposal of a new nomenclature.
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PMID:Update of the mutation spectrum and clinical correlations of over 360 mutations in eight genes that underlie the neuronal ceroid lipofuscinoses. 2199 Jan 11