Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0029089 (ophthalmoplegia)
 3,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report the clinical findings in 19 Finnish patients, including six pairs of siblings, with a new, early onset spinocerebellar ataxia. The slowly progressive clinical symptoms manifested between one and two years of age in previously healthy infants. The first manifestation of children at that age was clumsiness and loss of ability to walk. Ataxia, athetosis and muscle hypotonia with loss of deep tendon reflexes were discovered on clinical examination. By school age ophthalmoplegia and hearing loss were diagnosed, while sensory neuropathy developed by adolescence. In addition, an acute crisis with status epilepticus was a late manifestation. We found a marked decrease in sensory nerve condition velocities, a progressive loss of myelinated fibers in sural nerve specimen, and abnormal background activity in EEG with advancing age. The main finding in neuroradiological investigations was cerebellar atrophy. The occurrence of the disease in siblings and lack of manifestations in parents indicate recessive inheritance.
 ...
PMID:Infantile onset spinocerebellar ataxia with sensory neuropathy: a new inherited disease. 813 12

We recently described an infantile onset spinocerebellar ataxia (IOSCA) in 19 Finnish patients. The classification of hereditary ataxias of unknown etiology is difficult because of the heterogeneity of these diseases. The clinical course of IOSCA is homogeneous. Ataxia, muscle hypotonia, athetosis, and loss of deep tendon reflexes in the legs appeared around the age of 1 year. Ophthalmoplegia and deafness were found by school-age, and sensory axonal neuropathy and optic atrophy by adolescence. An acute crisis with epilepsy was a late manifestation. The female patients had hypogonadism. In order to define the type of hypogonadism and to exclude other endocrine defects we measured serum concentrations of SHBG, DHEAS, prolactine, testosterone/estradiol, FSH and LH in postpubertal patients. ACTH, hCG and GnRH tests were performed to both pre- and postpubertal patients. Growth was analysed, and the brain and pituitary region were examined with magnetic resonance imaging (MRI). The estradiol values were low and FSH and LH values were high in the female patients, which indicates that the hypogonadism was of the hypergonadotropic type. The growth of the female patients was steady without a significant pubertal growth acceleration. The growth and pubertal development of the male patients were normal. The adrenal cortical and thyroidea functions were normal in all patients.
 ...
PMID:Primary hypogonadism in females with infantile onset spinocerebellar ataxia. 855 18

Infantile onset spinocerebellar ataxia (IOSCA, MIM 271245) is a recessively inherited, progressive neurological disease, which we have described in 19 Finnish patients. The clinical symptoms of IOSCA include ataxia, athetosis, hypotonia, hearing deficit, ophthalmoplegia, sensory neuropathy, female hypogonadism, and epilepsy as a late manifestation. We have mapped the IOSCA locus to 10q24. In our two autopsy cases of IOSCA, the neuropathological findings were almost uniform. The cerebral hemispheres were quite well preserved, but the brain stem and the cerebellum were moderately atrophic. The most severe atrophic changes were seen in the spinal cord: in the dorsal roots, the posterior columns and the posterior spinocerebellar tracts. There was a severe neuronal loss in the dorsal nucleus (Clarke's column) of both cases and slight atrophy of the intermediolateral column in one case. The cerebellar peduncles, the inferior olives, the accessory cuneate nuclei and especially the dentate nuclei were atrophic and gliotic. The eighth cranial nerve and nucleus were atrophic. The ventral pontine nuclei and transverse fibers were slightly affected. Tegmental nuclei and tracts, especially sensory structures, were more severely affected. In mesencephalon, there was atrophy of the oculomotor nuclear complex and periaqueductal gray matter. The cerebellar cortex showed patchy atrophy. Degenerative changes were seen in dorsal root ganglia, and there was a severe axonal loss in the sural nerve. The neuropathological picture of IOSCA thus seems close to that reported in Friedreich's ataxia, another recessively inherited usually childhood-onset ataxia.
 ...
PMID:Infantile onset spinocerebellar ataxia with sensory neuropathy (IOSCA): neuropathological features. 987 82

Twinkle is a mitochondrial replicative helicase, the mutations of which have been associated with autosomal dominant progressive external ophthalmoplegia (adPEO), and recessively inherited infantile onset spinocerebellar ataxia (IOSCA). We report here a new phenotype in two siblings with compound heterozygous Twinkle mutations (A318T and Y508C), characterized by severe early onset encephalopathy and signs of liver involvement. The clinical manifestations included hypotonia, athetosis, sensory neuropathy, ataxia, hearing deficit, ophthalmoplegia, intractable epilepsy and elevation of serum transaminases. The liver showed mtDNA depletion, whereas the muscle mtDNA was only slightly affected. Alpers-Huttenlocher syndrome has previously been associated with mutations of polymerase gamma, a replicative polymerase of mtDNA. We show here that recessive mutations of the close functional partner of the polymerase, the Twinkle helicase, can also manifest as early encephalopathy with liver involvement, a phenotype reminiscent of Alpers syndrome, and are a new genetic cause underlying tissue-specific mtDNA depletion.
 ...
PMID:Recessive Twinkle mutations in early onset encephalopathy with mtDNA depletion. 1792 Nov 79

IOSCA is a difficult, progressive degenerative disease causing damage to the peripheral and central nervous system. All known 24 patients are Finnish. Initial symptoms include ataxia, athetosis, ophthalmoplegia, hearing disability and muscular hypotonia. Sensory axonal neuropathy and associated optic atrophy are typical of the disease, as well as primary hypergonadotropic hypogonadism in girls. The patients are progressively severely disabled from the age of approx. eighteen months. The pathogenesis is unknown and there is no curative treatment for the disease.
 ...
PMID:[IOSCA - Infantile onset spinocerebellar ataxia]. 2188 47

Whole exome sequencing combined with homozygosity mapping comprises a genetic diagnostic tool to identify genetic defects in families with multiple affected members, compatible with presumed autosomal recessively inherited neurometabolic/neurogenetic disease. These tools were applied to a family with two individuals manifesting ataxia, associated with peripheral sensory neuropathy, athetosis, seizures, deafness, and ophthalmoplegia. A novel homozygous missense mutation c.1366C>G (L456V) in C10orf2 (the Twinkle gene) was identified, confirming infantile onset spinocerebellar ataxia in the probands. Signs in infantile onset spinocerebellar ataxia follow a fairly distinct pattern, affecting early development, followed by ataxia and loss of skills. However, this very rare disease was previously reported only in Finland. We suggest that infantile onset spinocerebellar ataxia should be more frequently considered in the differential diagnosis of neurometabolic diseases in childhood. Next-generation sequencing and its use along with homozygosity mapping offer highly promising techniques for molecular diagnosis, especially in small families affected with very rare neurometabolic disorders such as infantile onset spinocerebellar ataxia.
 ...
PMID:Identification of a novel Twinkle mutation in a family with infantile onset spinocerebellar ataxia by whole exome sequencing. 2235 93

Crigler-Najjar Syndrome is an uncommon genetic disorder characterized by the elevation of unconjugated plasmatic bilirubin secondary to deficiency of the enzyme uridine diphosphate glucuronyltransferase (UDP-GT). We report a 19-years-old woman with the syndrome diagnosed during the neonatal period, when she developed a severe jaundice in the first 10 days of life, reaching unconjugated bilirubin levels of 29 mg/dl, with normal liver function tests. After transient response to phototherapy, the patient was referred to a tertiary medical center in which an extensive work up ruled out other etiologies and the diagnosis of type I Crigler-Najjar syndrome was established. Currently, the patient has a mild mental retardation. She is receiving homemade phototherapy 18 h per day with acceptable control of bilirubin levels. Many mutations have been associated with UDP-GT dysfunction resulting in a broad spectrum of the disease. When bilirubin rises above physiological limits, it permeates the hematoencephalic barrier, inducing bilirubin impregnation of basal ganglia with secondary neuronal damage and necrosis. The worst outcome, kernicterus, is characterized by mental retardation, central deafness, ophthalmoplegia, ataxia, athetosis, spasticity, seizures and death. First line therapy includes phototherapy, but definitive therapy is liver transplantation before the occurrence of neurological damage.
...
PMID:[Crigler-Najjar syndrome. Report of one case with a long term follow up]. 2486 Nov 23