Mutations in PCYT1A cause spondylometaphyseal dysplasia with cone-rod dystrophy.

Spondylometaphyseal dysplasia with cone-rod dystrophy is a rare autosomal-recessive disorder characterized by severe short stature, progressive lower-limb bowing, flattened vertebral bodies, metaphyseal involvement, and visual impairment caused by cone-rod dystrophy. Whole-exome sequencing of four individuals affected by this disorder from two Brazilian families identified two previously unreported homozygous mutations in PCYT1A. This gene encodes the alpha isoform of the phosphate cytidylyltransferase 1 choline enzyme, which is responsible for converting phosphocholine into cytidine diphosphate-choline, a key intermediate step in the phosphatidylcholine biosynthesis pathway. A different enzymatic defect in this pathway has been previously associated with a muscular dystrophy with mitochondrial structural abnormalities that does not have cartilage and/or bone or retinal involvement. Thus, the deregulation of the phosphatidylcholine pathway may play a role in multiple genetic diseases in humans, and further studies are necessary to uncover its precise pathogenic mechanisms and the entirety of its phenotypic spectrum.

How variable are hydroxyproline determinations made in different samples of the same liver?

OBJECTIVES: The haphazard distribution of fibrous tissue can interfere with quantitative methods for evaluating hepatic fibrosis. Inter-sample variation may represent a crucial issue when hydroxyproline measurement is used to quantify fibrosis. A comparative study of the hydroxyproline levels in normal and fibrotic rats is herein reported. MATERIAL AND METHODS: Twelve normal and 20 Capillaria hepatica-infected Wistar rats were used. Two fragments of the liver (A and B) of each rat were taken from separate areas and hydroxyproline measurements were made. Calculated differences in hydroxyproline measurements between samples from the same liver were analyzed by BOOTSTRAP. RESULTS: Differences in normal rats varied from 0.026 to 1.85 micromol of HP/g, in ten rats, the difference was less than 0.50 micromol. In infected rats, it varied from 0.04 to 2.86 micromol HP/g. Differences higher than 0.69 micromol/g were significant for normal rats (p<0.05) and above 1.22 micromol/g (p<0.05) for fibrotic rats. CONCLUSIONS: Hydroxyproline ratio in a normal liver kept a fair degree of reproducibility. In the presence of hepatic fibrosis, the levels of hydroxyproline may vary significantly between samples from a single liver and may have limited value in quantifying the extent of fibrosis.

Factors affecting visual loss and visual recovery in patients with pseudotumor cerebri syndrome.

PURPOSE: To investigate the frequency of visual loss (VL), possible predictive factors of VL, and improvement in patients with pseudotumor cerebri (PTC) syndrome. METHODS: We reviewed 50 PTC patients (43 females, seven males) who underwent neuro-ophthalmic examination at the time of diagnosis and after treatment. Demographic data, body mass index (BMI), time from symptom onset to diagnosis (TD), maximum intracranial pressure (MIP), occurrence of cerebral venous thrombosis (CVT), and treatment modalities were reviewed. VL was graded as mild, moderate, or severe on the basis of visual acuity and fields. Predictive factors for VL and improvement were assessed by regression analysis. RESULTS: The mean ± SD age, BMI, and MIP were 35.2 ± 12.7 years, 32.0 ± 7.5 kg/cm2, and 41.9 ± 14.5 cmH2O, respectively. Visual symptoms and CVT were present in 46 and eight patients, respectively. TD (in months) was <1 in 21, 1-6 in 15, and >6 in 14 patients. Patients received medical treatment with (n=20) or without (n=30) surgery. At presentation, VL was mild in 16, moderate in 12, and severe in 22 patients. Twenty-eight patients improved and five worsened. MIP, TD, and hypertension showed a significant correlation with severe VL. The best predictive factor for severe VL was TD >6 months (p=0.04; odds ratio, 5.18). TD between 1 and 6 months was the only factor significantly associated with visual improvement (p=0.042). CONCLUSIONS: VL is common in PTC, and when severe, it is associated with a delay in diagnosis. It is frequently permanent; however, improvement may occur, particularly when diagnosed within 6 months of symptom onset.

Relationship Between Pattern Electroretinogram, Frequency-Domain OCT, and Automated Perimetry in Chronic Papilledema From Pseudotumor Cerebri Syndrome.

PURPOSE: We evaluated the ability of transient pattern electroretinogram (PERG) parameters to differentiate between eyes with visual field (VF) loss and resolved papilledema from pseudotumor cerebri syndrome (PTC) and controls, to compare PERG and optical coherence tomography (OCT) with regard to discrimination ability, and to assess the correlation between PERG, frequency domain OCT (FD-OCT), and VF measurements. METHODS: The VFs and full-field stimulation PERGs based on 48 and 14-min checks were obtained from patients with PTC (n = 24, 38 eyes) and controls (n = 26, 34 eyes). In addition, FD-OCT peripapillary retinal nerve fiber layer (RNFL) and segmented macular layer measurements were obtained and correlation coefficients were determined. RESULTS: Compared to controls, PERG N95 and P50+N95 amplitude measurements with 48-minute checks were significantly reduced in eyes with resolved papilledema from PTC. Both PERG N95 amplitude and OCT parameters were able to discriminate papilledema eyes from controls with a similar performance. Significant correlations, ranging from 0.25 (P < 0.05) to 0.43 (P < 0.01) were found between PERG amplitude values and OCT-measured macular ganglion cell layer thickness, RNFL thickness, and total retinal thickness. The PERG amplitude also was significantly associated with VF sensitivity loss with correlation coefficients ranging from 0.24 (P < 0.05) and 0.35 (P < 0.01). CONCLUSIONS: The PERG measurements were able to detect neural loss in PTC eyes with resolved papilledema and were reasonably well correlated with OCT measurements and VF parameters. Thus, PERG may be a useful tool in the monitoring of retinal neural loss in eyes with active papilledema from PTC.

Factors affecting visual loss and visual recovery in patients with pseudotumor cerebri syndrome / Fatores que influenciam na perda e na recuperação visual de pacientes com a síndrome do pseudotumor cerebral

ABSTRACT Purpose: To investigate the frequency of visual loss (VL), possible predictive factors of VL, and improvement in patients with pseudotumor cerebri (PTC) syndrome. Methods: We reviewed 50 PTC patients (43 females, seven males) who underwent neuro-ophthalmic examination at the time of diagnosis and after treatment. Demographic data, body mass index (BMI), time from symptom onset to diagnosis (TD), maximum intracranial pressure (MIP), occurrence of cerebral venous thrombosis (CVT), and treatment modalities were reviewed. VL was graded as mild, moderate, or severe on the basis of visual acuity and fields. Predictive factors for VL and improvement were assessed by regression analysis. Results: The mean ± SD age, BMI, and MIP were 35.2 ± 12.7 years, 32.0 ± 7.5 kg/cm2, and 41.9 ± 14.5 cmH2O, respectively. Visual symptoms and CVT were present in 46 and eight patients, respectively. TD (in months) was <1 in 21, 1-6 in 15, and >6 in 14 patients. Patients received medical treatment with (n=20) or without (n=30) surgery. At presentation, VL was mild in 16, moderate in 12, and severe in 22 patients. Twenty-eight patients improved and five worsened. MIP, TD, and hypertension showed a significant correlation with severe VL. The best predictive factor for severe VL was TD >6 months (p=0.04; odds ratio, 5.18). TD between 1 and 6 months was the only factor significantly associated with visual improvement (p=0.042). Conclusions: VL is common in PTC, and when severe, it is associated with a delay in diagnosis. It is frequently permanent; however, improvement may occur, particularly when diagnosed within 6 months of symptom onset. .

RESUMO Objetivo: Investigar a frequência de perda visual (PV) e os possíveis fatores preditivos para perda e para melhora visual em pacientes com a síndrome do pseudotumor cerebral (SPC). Métodos: Foram revisados 50 pacientes com SPC submetidos a exame neuroftalmológico no momento do diagnóstico e após o tratamento. Dados demográficos, índice de massa corpórea (IMC), tempo decorrido entre o início dos sintomas e o diagnóstico (TD), pressão intracraniana máxima (PIM), ocorrência de trombose venosa cerebral (TVC), e as modalidades de tratamento foram revisadas. PV foi graduada em discreta, moderada e grave, baseada na acuidade e no campo visual. Fatores preditivos para perda e melhora visual foram avaliados por análise de regressão linear. Resultados: Quarenta e três pacientes eram do sexo feminino. A média de idade, o IMC e a PIM (± desvio padrão) foram: 35,2 ± 12,7 anos, 32,0 ± 7,5 kg/cm2 e 41,9 ± 14,5 cmH2O, respectivamente. Sintomas visuais estavam presentes em 46 e TVC em 8 pacientes. TD (em meses) foi <1 em 21, 1-6 em 15 e >6 em 14 pacientes. Pacientes receberam tratamento clinico apenas (n=30) ou associado a tratamento cirúrgico (n=20). Na apresentação a PV era discreta em 16, moderada em 12 e grave em 22 pacientes. Vinte e oito pacientes melhoraram e 5 pioraram. PIM, TD e hipertensão arterial correlacionaram significativamente com PV grave. O melhor fator preditivo para PV grave foi o TD>6 meses (p=0,04; razão de chances 5,18). TD entre 1 e 6 meses foi o único fator significativamente associado com melhora visual após tratamento (p=0,042). Conclusões: Perda visual é comum na SPC e quando grave se mostra relacionado a atraso no diagnóstico. É usualmente permanente mas pode haver melhora visual especialmente quando a doença é diagnosticada nos primeiros 6 após o início dos sintomas. .