Background: Isolated functional methionine synthase defi-ciency occurs in the cblE and cblG defects of methylcobalamin metabolism and is one of a number of c auses of severely elevated plasma homocysteine. Clinical fe...Background: Isolated functional methionine synthase defi-ciency occurs in the cblE and cblG defects of methylcobalamin metabolism and is one of a number of c auses of severely elevated plasma homocysteine. Clinical features are predominan tly of a neurological nature but also include functional restriction of the visual system manifesting as loss of visual acui ty and nystagmus. As yet, the origin and pathogenesis of impaired vision have no t been explained. Materials and methods: We investigated a patientwhowas proven by complementation analysis in cultured fibroblasts to belong to the cblG comple mentation group. Ganzfeld electroretinograms (ERG)-and flash visual evoked pote ntials (VEP) were recorded over a period of 4 years. Results: Amplitudes of all International Society for Clinical Electrophysiology of Vision (ISCEV) standard responses were below normal. The greatest reductions were of rod response to 24 μV, of standard combined response (SC) b-wave to 120 μV, of oscillatory poten tials (OP) to 5 μV, of cone response b-wave to 35 μV, and of 30Hz flicker res ponse to 8 μV. Except for SC and cone a-waves at age 2.5 and 3.5 years, as wel l as cone b-wave at 3.5 years, amplitudes remained at a subnormal level at foll ow-up examinations. Implicit times were slightly prolonged (SC b-wave 6 ms, OP s 2 ms, cone b-wave 2 ms, 30 Hz flicker 4 ms) or fell within the normal range. Responses of the flash VEP were severely deformed but reproducible. Conclusions: This is the first report of detailed investigations of the visual system in a p atient with isolated methionine synthase deficiency. Reduced oscillatory potenti als suggest microvascular damage to the retina through homocysteine. Decreased p hotoreceptor function as well as ganglion cell loss as indicated by pathological flash VEPs may reflect a cytotoxic impact of homocysteine on neurons of the vis ual pathway.展开更多
Purpose: To quantify retinal function longitudinally and crosssectionally in p atients with autosomal-recessive early-onset severe retinal dystrophy (EOSRD) associated with RPE65 mutations. Subjects and methods: The o...Purpose: To quantify retinal function longitudinally and crosssectionally in p atients with autosomal-recessive early-onset severe retinal dystrophy (EOSRD) associated with RPE65 mutations. Subjects and methods: The ocular phenotype was characterized in four children from three families up to the second decade of li fe, and in three siblings from one family aged 43-54 years carrying compound he terozygous or homozygous mutations in RPE65. Standard clinical examination inclu ded colour vision testing, fundus photography and Goldmann visual fields (GVF). Full-field ERGs (in all) and multifocal ERGs (in two patients) were also record ed. Visual performance and fundus appearance were compared to literature data. R esults: In childhood, visual acuity (VA) ranged from 0.1 to 0.3, and GVF for tar get V4 was well preserved. VA and GVF were measurable in only one of the three a dult siblings. Nystagmus was present in two of four children and two of three ad ults. Photophobia was absent in childhood and developed in adulthood. Funduscopi c changes were discrete during the first decade of life in three of four childre n; one patient had clear macular changes already at age 5 years. All three adult siblings had distinct retinal changes including the macula. Bone spicules were not a feature. Residual colour vision was present in all patients with measurabl e VA. Rod ERGs were absent at any age; cone ERGs were detectable in early childh ood. To date, VA data have been reported in 51 patients, visual fields in 29 pat ients, and a detailed fundus description in 34 patients. For all three parameters, data were compara ble to the results in our patient cohort. Conclusion: In childhood, patients wit h RPE65 mutations have better visual functions than typically seen in Leber cong enital amaurosis. The phenotype shows a common progressive pattern with intrafam ilial and interfamilial variation. The data suggest a preserved retinal morpholo gy at young ages, arguing for vision-restoring gene therapy trials in childhood .展开更多
Background: Duane retraction syndrome (DURS) accounts for 1- 4% of all cases of strabismus. Approximately 90% of the cases are sporadic with a preponderance for females and the left eye. Many associated ocular and sys...Background: Duane retraction syndrome (DURS) accounts for 1- 4% of all cases of strabismus. Approximately 90% of the cases are sporadic with a preponderance for females and the left eye. Many associated ocular and systemic findings have been described. Recently, mutations of SALL4 have been found in patients with autosomal- dominantly inherited Okihiro syndrome (DURS associated with forearm malformations). The aim of this study was the clinical examination of patients with isolated sporadic DURS and the molecular genetic analysis of SALL4 in these patients. Subjects and Methods: Twenty- five patients with non- familial DURS (aged 1- 75 years, 16 female, 9 male) were examined clinically and were interviewed concerning associated pathologies. DNA was prepared from peripheral lymphocytes, and the complete coding region of SALL4 was sequenced. Results: In 18 patients DURS affected the left eye, in four the right eye, and was bilateral in three patients. One patient had fused vertebrae, one had a cone- rod- dystrophy. No hearing impairments or malformation of the upper limbs were observed. No mutation in the coding region of SALL4 could be detected. Discussion: Associated conditions in DURS patients most commonly involve the ear, the spinal column, the kidneys and the heart and the upper limbs. No mutations in SALL4 could be detected in patients with isolated sporadic DURS as opposed to findings in familial Okihiro syndrome. However, Okihiro syndrome shows marked intra- and interfamilial variability, suggesting that in rare cases of isolated DURS a causative SALL4 mutation may be found.展开更多
文摘Background: Isolated functional methionine synthase defi-ciency occurs in the cblE and cblG defects of methylcobalamin metabolism and is one of a number of c auses of severely elevated plasma homocysteine. Clinical features are predominan tly of a neurological nature but also include functional restriction of the visual system manifesting as loss of visual acui ty and nystagmus. As yet, the origin and pathogenesis of impaired vision have no t been explained. Materials and methods: We investigated a patientwhowas proven by complementation analysis in cultured fibroblasts to belong to the cblG comple mentation group. Ganzfeld electroretinograms (ERG)-and flash visual evoked pote ntials (VEP) were recorded over a period of 4 years. Results: Amplitudes of all International Society for Clinical Electrophysiology of Vision (ISCEV) standard responses were below normal. The greatest reductions were of rod response to 24 μV, of standard combined response (SC) b-wave to 120 μV, of oscillatory poten tials (OP) to 5 μV, of cone response b-wave to 35 μV, and of 30Hz flicker res ponse to 8 μV. Except for SC and cone a-waves at age 2.5 and 3.5 years, as wel l as cone b-wave at 3.5 years, amplitudes remained at a subnormal level at foll ow-up examinations. Implicit times were slightly prolonged (SC b-wave 6 ms, OP s 2 ms, cone b-wave 2 ms, 30 Hz flicker 4 ms) or fell within the normal range. Responses of the flash VEP were severely deformed but reproducible. Conclusions: This is the first report of detailed investigations of the visual system in a p atient with isolated methionine synthase deficiency. Reduced oscillatory potenti als suggest microvascular damage to the retina through homocysteine. Decreased p hotoreceptor function as well as ganglion cell loss as indicated by pathological flash VEPs may reflect a cytotoxic impact of homocysteine on neurons of the vis ual pathway.
文摘Purpose: To quantify retinal function longitudinally and crosssectionally in p atients with autosomal-recessive early-onset severe retinal dystrophy (EOSRD) associated with RPE65 mutations. Subjects and methods: The ocular phenotype was characterized in four children from three families up to the second decade of li fe, and in three siblings from one family aged 43-54 years carrying compound he terozygous or homozygous mutations in RPE65. Standard clinical examination inclu ded colour vision testing, fundus photography and Goldmann visual fields (GVF). Full-field ERGs (in all) and multifocal ERGs (in two patients) were also record ed. Visual performance and fundus appearance were compared to literature data. R esults: In childhood, visual acuity (VA) ranged from 0.1 to 0.3, and GVF for tar get V4 was well preserved. VA and GVF were measurable in only one of the three a dult siblings. Nystagmus was present in two of four children and two of three ad ults. Photophobia was absent in childhood and developed in adulthood. Funduscopi c changes were discrete during the first decade of life in three of four childre n; one patient had clear macular changes already at age 5 years. All three adult siblings had distinct retinal changes including the macula. Bone spicules were not a feature. Residual colour vision was present in all patients with measurabl e VA. Rod ERGs were absent at any age; cone ERGs were detectable in early childh ood. To date, VA data have been reported in 51 patients, visual fields in 29 pat ients, and a detailed fundus description in 34 patients. For all three parameters, data were compara ble to the results in our patient cohort. Conclusion: In childhood, patients wit h RPE65 mutations have better visual functions than typically seen in Leber cong enital amaurosis. The phenotype shows a common progressive pattern with intrafam ilial and interfamilial variation. The data suggest a preserved retinal morpholo gy at young ages, arguing for vision-restoring gene therapy trials in childhood .
文摘Background: Duane retraction syndrome (DURS) accounts for 1- 4% of all cases of strabismus. Approximately 90% of the cases are sporadic with a preponderance for females and the left eye. Many associated ocular and systemic findings have been described. Recently, mutations of SALL4 have been found in patients with autosomal- dominantly inherited Okihiro syndrome (DURS associated with forearm malformations). The aim of this study was the clinical examination of patients with isolated sporadic DURS and the molecular genetic analysis of SALL4 in these patients. Subjects and Methods: Twenty- five patients with non- familial DURS (aged 1- 75 years, 16 female, 9 male) were examined clinically and were interviewed concerning associated pathologies. DNA was prepared from peripheral lymphocytes, and the complete coding region of SALL4 was sequenced. Results: In 18 patients DURS affected the left eye, in four the right eye, and was bilateral in three patients. One patient had fused vertebrae, one had a cone- rod- dystrophy. No hearing impairments or malformation of the upper limbs were observed. No mutation in the coding region of SALL4 could be detected. Discussion: Associated conditions in DURS patients most commonly involve the ear, the spinal column, the kidneys and the heart and the upper limbs. No mutations in SALL4 could be detected in patients with isolated sporadic DURS as opposed to findings in familial Okihiro syndrome. However, Okihiro syndrome shows marked intra- and interfamilial variability, suggesting that in rare cases of isolated DURS a causative SALL4 mutation may be found.
