Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We reported the first case of typical infantile-type neuronal ceroid-lipofuscinosis (INCL) in Japan. The patient was a 1-year-old girl presenting with rapidly progressive psychomotor deterioration and blindness. Muscular hypotonia, microcephaly and myoclonic jerks became marked with the progression of her disease. Diminution in amplitude of EEG, VEP and ERG was prominent in the initial stage, but ABR was normal. MRI showed progressive brain atrophy. Electron microscopic examination of the biopsied skin revealed granular matrix, the specific inclusion bodies, in the epithelial cell of sweet glands. Many sea-blue histiocytes were demonstrated in her bone marrow samples. INCL is a common progressive encephalopathy in the Scandinavian countries, but a typical case had not yet been fully reported in Japan. This prompted us to report our case. Future reports are need for the study of INCL in Japan.
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PMID:[The first case of infantile type neuronal ceroid-lipofuscinosis in Japan]. 141 75

There are several clinically distinct forms of neuronal ceroid lipofuscinosis whose presentation and pathology are usually homogeneous within families. Several atypical variants have also been reported. We have studied an inbred sibship in which neuronal ceroid lipofuscinosis appeared to present in two completely different ways. In the proband, the course was compatible with a somewhat atypical juvenile variant. Ataxia and spasticity started at 4.5 years, followed by blindness with optic atrophy, intractable seizures, dementia, and death at 14 years. Atypical features included areflexia, hypotonia, and ataxia. Electron microscopic studies of her skin and her rectal ganglion cells showed lucent, dense, and fingerprint inclusions that were also found in the central nervous system at autopsy. Her brother and sister developed difficulty walking at ages 8.5 and 10.5 years and are alive at 24 and 18 years. They presented with slowly progressive spinocerebellar degeneration with sensorimotor neuropathy without dementia, seizures, or visual impairment. Lysosomal enzymes and lipoprotein analysis were normal in all three siblings and their parents. Elevated dolichol in the urine and lucent, dense, and fingerprint inclusions in skin, cutaneous nerve, buffy coat lymphocytes in both siblings and in the sural nerve of the brother suggest that their disease may represent a novel phenotype of neuronal ceroid lipofuscinosis. While it is possible that two different recessive genes may be segregating in this consanguineous family, we cannot dismiss the possibility that variability of gene expression may account for the divergent phenotypes.
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PMID:Spino-cerebellar degeneration with polyneuropathy associated with ceroid lipofuscinosis in one family. 342 77

We report on a 13-year-old girl with late infantile neuronal ceroid lipofuscinosis (NCL) in whom PET scanning with [18F]-2-fluoro-2-deoxy-D-glucose ([18F]/FDG) was performed. Early psychomotor development was normal. At the age of 2 years, neurological signs such as hypotonia and incoordination appeared, followed by visual failure and ataxia. At the age of 4, funduscopic examination showed macular degeneration and papillary atrophy. At the age of 9, myoclonic jerks were observed; subsequently, generalized seizures together with failing vision, mental deterioration, and visual and auditory hallucinations appeared. Brain MRI showed severe cortical and subcortical atrophy. A skin biopsy detected the presence of 'finger-print' inclusions in the cytoplasm of smooth muscle fibers. Late infantile NCL (Jansky-Bielschowsky disease) was diagnosed. FDG/PET revealed a severe reduction of metabolism in all the cortical and subcortical structures. A regional analysis of the distribution of the tracer revealed marked bilateral hypometabolism, particularly in calcarine, lateral, occipital, and temporal cortices and in the thalamus.
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PMID:Positron emission tomography in neuronal ceroid lipofuscinosis (Jansky-Bielschowsky disease): a case report. 757 68

Clinical features and results of the blood DNA analysis are reported of a child affected with a distinct phenotype of the late infantile form of neuronal ceroid-lipofuscinosis (LINCL). He was affected by microcephaly and hypotonia since the fourth month of life; acquisition of motor and language abilities was severely impaired, and a disorder of communication with stereotyped movements followed. By age four, he developed signs and symptoms of progressive myoclonic encephalopathy along with motor and cognitive deterioration. Extrapyramidal signs were associated with neuroradiological findings of marked atrophy of the caudate nucleus. Specific curvilinear bodies were observed in blood lymphocytes and skin biopsy. Homozygous, nonsense mutation in the CLN2 gene was found giving origin to an Arg208stop, which produces an early transcription termination with loss of translation of about 50% of the gene product. Any relationship between the severe clinical features of our patient and the homozygous mutation here reported must be investigated on a larger number of LINCL patients bearing the same mutation.
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PMID:A CLN2 gene nonsense mutation is associated with severe caudate atrophy and dystonia in LINCL. 1107 Nov 45

Epilepsies associated with inborn errors of metabolism (IEM) represent a major challenge. Seizures rarely dominate the clinical presentation, which is more frequently associated with other neurological symptoms, such as hypotonia and/or cognitive disturbances. Although epilepsy in IEM can be classified in various ways according to pathogenesis, age of onset, or electroclinical presentation, the most pragmatic approach is determined by whether they are accessible to specific treatment or not. The main potentially treatable causes comprise vitamin B6 (pyridoxine deficiency), biotine, and GLUT1 deficiency (GLUT1DS) syndromes. Folinic acid-dependent seizures are allelic with pyridoxine dependency. Incompletely treatable IEMs include pyridoxal phosphate, serine, and creatine deficiencies. The main IEMs that present with epilepsy but offer no specific treatment are nonketotic hyperglycinemia, mitochondrial disorders, sulfite oxidase deficiency, ceroid-lipofuscinosis, Menkes disease, and peroxisomal disorders.
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PMID:Epilepsy in inborn errors of metabolism. 2362 1

Homozygous mutation of TBC1 domain-containing kinase (TBCK) is the cause of a very recently defined severe childhood disorder, which is characterized by severe hypotonia, global developmental delay, intellectual disability, epilepsy, characteristic facies and premature death. The link between TBCK loss of function and symptoms in patients with TBCK deficiency disorder (TBCK-DD) remains elusive. Here we demonstrate for the first time the histopathological characteristics of TBCK deficiency consisting of 1) a widespread and massive accumulation of lipofuscin storage material in neurons of the central nervous system without notable neuronal degeneration, 2) storage deposits in few astrocytes, 3) carbohydrate-rich deposits in brain, spleen and liver and 4) vacuolated lymphocytes. Biochemical examinations ruled out more than 20 known lysosomal storage diseases. These investigations strikingly uncover TBCK-DD as a novel type of lysosomal storage disease which is characterized by different storage products rather than one specific type of accumulated material. Due to the clear predominance of intraneuronal lipofuscin storage material and the characteristic clinical presentation we propose to classify this disease as a new subtype of neuronal ceroid lipofuscinosis (CLN15). Our results and previous reports suggest an autophagosomal-lysosomal dysfunction caused by enhanced mTORC1-mediated autophagosome formation and reduced Rab-mediated autophagosome-lysosome fusion, thus disclosing potential novel targets for therapeutic approaches in TBCK-DD.
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PMID:Homozygous TBC1 domain-containing kinase (TBCK) mutation causes a novel lysosomal storage disease - a new type of neuronal ceroid lipofuscinosis (CLN15)? 3059 Oct 81

Neuronal ceroid lipofuscinosis (NCL) is a lysosomal storage disorder that causes progressive neurodegenerative disease as a result of storage in neurons and other cells. Late infantile type (NCL Type 2) of NCL, which is the most common neurodegenerative disease in childhood, is characterised by a homozygous mutation in the tripeptidyl peptidase-1 (TPP-1) gene. A male infant was referred to our neonatal intensive care unit (NICU) on 26th day of life with a diagnosis of metabolic disease. He was intubated. He was hypotonic and newborn reflexes were not present. Cranial magnetic resonance (MR) imaging revealed severe atrophy and delayed myelination of cerebellum and cerebral hemispheres. A novel homozygous pathological mutation was detected in exon 9 of the TPP-1 gene. With this case, it should be kept in mind that NCL may rarely start early in neonatal period and should be suspected in newborns with cerebral and cerebellar atrophy for early diagnosis. Key Words: Hypotonia, Lysosomal storage diseases, Metabolic disease, Neuronal ceroid lipofuscinosis, Newborn.
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PMID:A Case with Neonatal-onset Type 2 Neuronal Ceroid Lipofuscinosis: A Novel Mutation. 3258 Aug 58