scholarly journals Clinical and genetic analysis of two Chinese families with vitamin D-dependent rickets type IA and follow-up

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Yunfei Li ◽  
Xin Yuan ◽  
Ruimin Chen ◽  
Xiangquan Lin ◽  
Huakun Shangguan ◽  
...  

Abstract Objective Vitamin D-dependent rickets type IA (VDDR-IA) is a rare autosomal recessive disorder characterized by the early onset of severe rickets. The objectives of this study were twofold: (1) to analyze the clinical characteristics and therapy of two patients with VDDR-IA from two separate Chinese families, and (2) investigate the CYP27B1 gene mutations in two large pedigrees. Methods Medical history, clinical manifestations, physical examination, radiological findings and laboratory data were analyzed from two patients with VDDR-IA. Serum 1, 25-dihydroxyvitamin D [1, 25-(OH)2D3] of the two patients and their respective families were measured by ELISA and blood samples from both families was obtained for CYP27B1 gene sequence. Results Two patients had typical manifestations and radiological evidence of rickets. Laboratory data showed hypocalcaemia and hypophosphataemia, along with high levels of serum alkaline phosphatase, parathyroid hormone and 25-hydroxyvitamin D3. However, serum 1,25-(OH)2D3 level were low in the patients but normal in their family members. Genetic sequence identified two patients were homozygous for a duplication mutation in exon 8 of CYP27B1 gene (c.1319_1325dupCCCACCC, p.Phe443Profs * 24). After treating with calcitriol and calcium, there was biochemical improvement with normalization of serum calcium and phosphorus, and radiographic evidence of compensatory skeletal mineralization. One patient developed nephrocalcinosis during follow-up. Conclusions This study identified a recurrent seven-nucleotide insertion of CYP27B1 in two large pedigrees, and compared the clinical characteristics and individual therapy of two affected patients. Additionally, our experience further supports the notion that nephrocalcinosis can occur even on standard doses of calcitriol and oral calcium, and normal level of serum calcium, phosphorus, PTH and 25-(OH)D3.

2020 ◽  
Author(s):  
Wenzhi ZHANG ◽  
Hui LI ◽  
Jingzhen LIU ◽  
Jiawei XU ◽  
Jinjin HAO ◽  
...  

Abstract The knowledge of clinical characteristics and prognosis of pediatric acute megakaryocytic leukemia (AMKL) with or without acquired +21 was limited. We reported 15 AMKL pediatric patients without Down Syndrome (four cases with acquired +21 and 11 cases without acquired +21) with the clinical manifestations, laboratory data, and prognosis. The clinical features and laboratory data between patients with acquired +21 and patients without acquired +21 are similar. As for prognosis, three of the 11 cases without acquired +21 obtained complete remission (CR) after 1st induction. The median follow-up time of the 11 cases was 9 months. Among four cases with acquired +21, one case gave up treatment during 1st induction, one obtained CR after 1st induction and was still alive after 49 months of follow-up. One case obtained CR after 2nd induction and was still alive for 15 months of follow-up after bone marrow transplantation, the other patient was planning for allogeneic hematopoietic stem cell transplantation (HSCT) without CR. The median follow-up time of the four cases was 12 months. None relapsed in our study. In conclusion, acquired trisomy 21 may not be an indicator for poor prognosis. Cytogenetics analysis can help us for diagnosis stratification, prognostic judgment and individualized treatment of AMKL.


BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Nilanka Wickramasinghe ◽  
Dhanushka Dasanayake ◽  
Neelika Malavige ◽  
Rajiva de Silva ◽  
Thashi Chang

Abstract Background Autoimmune encephalitis (AE) is now considered a main, potentially curable cause of encephalitis, but remains conspicuously underreported from South Asia. We studied the clinical characteristics in relation to their antibody status and outcomes of patients presenting with AE in Sri Lanka. Methods Patients admitting to government hospitals who were clinically suspected of AE by an on-site neurologist were prospectively recruited over a period of 12 months. Sera and cerebrospinal fluid were tested for NMDAR, AMPAR1, AMPAR2, LGI1, CASPR2, GABARB1/B2 antibodies (Ab) using commercial cell-based assays. Demographic, clinical and laboratory data were compiled into an investigator-administered proforma. Patients were reviewed at 1 year follow up either in person or via telephone. Results One-hundred and forty-two patients from 21 of 25 districts in Sri Lanka (median age = 20.5 years; range 1–86 years; females = 61.3%) were recruited. Of them, 65 (45.8%; median age = 19 years; range 1–86 years; females = 64.6%) fulfilled diagnostic criteria for probable NMDAR-antibody encephalitis (NMDARE) and 6 (4.2%; median age = 44 years; range 28–71 years; females = 83.3%) limbic encephalitis (LE). Abnormal behaviour (95.3%), seizures (81.5%) and movement disorders (69.2%) were the most frequent clinical manifestations of probable NMDARE. NMDAR-antibodies were detectable in 29 (44.6%) and not detectable in 36 in CSF of probable-NMDARE patients. Abnormal EEG was more frequent (p = 0.003) while a worse outcome (OR = 2.78; 95% CI = 0.88–9.09) and deaths (OR = 2.38; 95% CI = 0.67–8.33) were more likely in antibody-negative than antibody-positive probable-NMDARE. Most patients with LE had amnesia (50%) and/or confusion (100%) with agitation (83.3%) and seizures (100%) but none had detectable antibodies to any of the antigens tested. Conclusions NMDARE is the commonest type of AE among South Asians as is the case worldwide. Clinical presentations of NMDARAb-positive and NMDARAb-negative AE patients do not significantly differ but EEG may be a useful marker of an autoimmune basis for psychiatric symptoms.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1563.3-1563
Author(s):  
H. Tamaki ◽  
S. Fukui ◽  
T. Nakai ◽  
G. Kidoguchi ◽  
S. Kawaai ◽  
...  

Background:Currently it is hypothesized that many systemic autoimmune diseases occur due to environmental risk factors in addition to genetic risk factors. Anti-Neutrophil Cytoplasmic Antibody (ANCA) is mainly associated with three systemic autoimmune disease including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA). It is known that ANCA can be positive before clinical symptoms in patients with known diagnosis of GPA and ANCA titers rise before clinical manifestations appear. However, prevalence of ANCA among general population is not well known. It has not been described as well how many of people with positive ANCA eventually develop clinical manifestations of ANCA associated Vasculitis.Objectives:This study aims to estimate prevalence of ANCA in general population without ANCA associated Vasculitis. It also describes natural disease course of people with positive ANCA without ANCA associated Vasculitis. Risk factors for positive ANCA are also analyzed.Methods:This is a single center retrospective study at Center for Preventive Medicine of St. Luke’s International Hospital in Tokyo. ANCA was checked among the patients who wished to between 2018 and 2019. St. Luke’s Health Check-up Database (SLHCD) was utilized to collect the data. The patients whose serum was measured for ANCA were identified. The data for basic demographics, social habits, dietary habits and laboratory data were extracted. The charts of the patients with positive ANCA were reviewed.Results:Sera of total 1204 people were checked for ANCA. Of these 1204 people, 587 (48.8%) are male and the mean age was 55.8 years (32.6 to 79). There were total 11 patients with positive ANCA. Myeloperoxidase ANCA (MPO-ANCA) was positive for 3 patients and proteinase 3 ANCA (PR3-ANCA) was positive for 8 patients. Of these 11 patients, 5 were male (45.5%) and the mean age was 54.6 years. Two patients had history of autoimmune disease (primary biliary cirrhosis and ulcerative colitis). Five patients were evaluated by rheumatologists with the median follow-up period of 274 days. None of them developed clinical signs and symptoms of ANCA associated Vasculitis. Four out of five patients had ANCA checked later, two of which turned negative. The prevalence of ANCA in this cohort was 0.9% (95% confidence interval [95% CI]: 0.5% to 1.6%). Univariate analysis was performed to identify risk factors of positive ANCA. The variables analyzed include age, gender, body mass index (BMI), smoking habits, alcohol intake, dietary habits (fruits, fish, red meat), hypertension, dyslipidemia, and laboratory data. None of these variables demonstrated statistically significant differences except for positive rheumatoid factor (ANCA positive group: 33 % vs ANCA negative group: 9.1%, p value = 0.044).Conclusion:The prevalence of ANCA in this cohort was 0.9% (95% CI: 0.5% to 1.6%). None of them who had a follow-up developed ANCA associated Vasculitis during the follow-up period. Longer follow-up and more patients are necessary to determine natural course of people with positive ANCA.Disclosure of Interests:None declared


PEDIATRICS ◽  
1959 ◽  
Vol 24 (2) ◽  
pp. 258-269
Author(s):  
David W. Smith ◽  
Robert M. Blizzard ◽  
Harold E. Harrison

A case of idiopathic hypercalcemia present from early infancy and diagnosed at 5 years of age is reported in which the serum assay of vitamin D indicated elevated levels. After discontinuation of supplemental vitamin D and a diet low in calcium the concentrations of calcium and vitamin D in the serum gradually returned to normal over a period of 18 months. Roentgenograms of the bones showed evidence of demineralization rather than increased density as reported in other cases of "idiopathic" hypercalcemia. During a subsequent 2-year follow-up the patient has maintained a normal serum calcium. The etiology is discussed with particular reference to the role of vitamin D in this case


2021 ◽  
Vol 8 (30) ◽  
pp. 2797-2803
Author(s):  
Rasheed Khan M ◽  
Thivyah Prabha A.G ◽  
Siva Kumar K

BACKGROUND Mineral metabolism is frequently disturbed in thyroid dysfunctions. Among thyroid dysfunctions, hypothyroidism is one of the most common form resulting from the deficiency of thyroid hormones. Studies done on serum calcium, phosphorus and magnesium in hypothyroid patients earlier have conflicting results. Hence the present study has been undertaken to study the levels of serum calcium, phosphorus, and magnesium among hypothyroid patients and analyse their correlation with thyroid stimulating hormone (TSH). METHODS The case control study was conducted in the Department of Biochemistry in Trichy SRM Medical College Hospital and Research Centre for a period of 6 months from 2017 January to July 2017. The study was undertaken involving 50 hypothyroid cases and 50 healthy volunteers as controls after proper ethical clearance and informed consent of all the study subjects. Serum calcium, phosphorus and magnesium were measured along with tri-iodothyronine (FT3), tetra-iodothyronine (FT4) and TSH among all study subjects. Statistical analysis of data was done using statistical package for social sciences (SPSS) software. RESULTS The mean value of serum total calcium and total magnesium was lower among hypothyroid cases and phosphorus value was increased as compared to controls. (P < 0.001) Statistically significant negative correlation was observed between serum calcium, magnesium and TSH among hypothyroid cases. Statistically significant positive correlation was observed between serum phosphorus and TSH among hypothyroid cases. CONCLUSIONS Among hypothyroid patients the values of serum calcium, magnesium and phosphorus is significantly altered. Thyroid disorders have an important role in bone and mineral metabolism. Thus, monitoring of these minerals among hypothyroid patients in regular follow up may effectively improve the clinical manifestations in them. Hence, monitoring of mineral status of the hypothyroid patients on follow-up will be of benefit to the patients. KEYWORDS Hypothyroidism, Calcium, Phosphorus, Magnesium, Minerals


2005 ◽  
Vol 90 (4) ◽  
pp. 2122-2126 ◽  
Author(s):  
Andrew Grey ◽  
Jenny Lucas ◽  
Anne Horne ◽  
Greg Gamble ◽  
James S. Davidson ◽  
...  

Abstract Vitamin D insufficiency is common in patients with primary hyperparathyroidism (PHPT) and may be associated with more severe and progressive disease. Uncertainty exists, however, as to whether repletion of vitamin D should be undertaken in patients with PHPT. Here we report the effects of vitamin D repletion on biochemical outcomes over 1 yr in a group of 21 patients with mild PHPT [serum calcium &lt;12 mg/dl (3 mmol/liter)] and coexistent vitamin D insufficiency [serum 25 hydroxyvitamin D [25(OH)D] &lt;20 μg/liter (50 nmol/liter)]. In response to vitamin D repletion to a serum 25(OH)D level greater than 20 μg/liter (50 nmol/liter), mean levels of serum calcium and phosphate did not change, and serum calcium did not exceed 12 mg/dl (3 mmol/liter) in any patient. Levels of intact PTH fell by 24% at 6 months (P &lt; 0.01) and 26% at 12 months (P &lt; 0.01). There was an inverse relationship between the change in serum 25(OH)D and that in intact PTH (r = −0.43, P = 0.056). At 12 months, total serum alkaline phosphatase was significantly lower, and urine N-telopeptides tended to be lower than baseline values (P = 0.02 and 0.13, respectively). In two patients, 24-h urinary calcium excretion rose to exceed 400 mg/d, but the group mean 24-h urinary calcium excretion did not change. These preliminary data suggest that vitamin D repletion in patients with PHPT does not exacerbate hypercalcemia and may decrease levels of PTH and bone turnover. Some patients with PHPT may experience an increase in urinary calcium excretion after vitamin D repletion.


2016 ◽  
Vol 64 (4) ◽  
pp. 929.2-930
Author(s):  
V Jetty ◽  
G Duhon ◽  
P Shah ◽  
M Prince ◽  
K Lee ◽  
...  

BackgroundIn ∼85–90% of statin intolerant patients, vitamin D deficiency (serum 25 (OH) D <32 ng/ml) is a reversible cause of statin intolerance, usually requiring 50,000 to 100,000 units of vitamin D/week continuously to normalize serum vitamin D, and thus successfully allow reinstitution of statins which previously could not be tolerated because of myalgia-myositis.Specific AimIn 274 statin intolerant patients, all with low entry serum vitamin D (<32 ng/ml, median 21 ng/ml), we assessed safety and efficacy of vitamin D supplementation (50,000–100,000 units/week) over treatment periods of 3 months (n=274), 3 and 6 months (n=161), 3, 6, and 9 months (n=58), and 3, 6, 9, and 12 months (n=22).ResultsIn the 385 patients with 3 month follow-up, taking mean 61,000 and median 50,000 IU of vitamin D3/week, median serum vitamin D rose from 20 to 42 ng/ml (p<0.0001); vitamin D became high (>100 ng/ml) but not toxic-high (>150 ng/ml) in 4 patients (1.0%) (101, 102, 106, 138 ng/ml). Median serum calcium was unchanged from entry (9.6 mg/dl) to 9.6 at 3 months. On vitamin D supplementation, the trend of change in serum calcium from normal-to-high or from high-to-normal did not significantly differ (McNemar S=1.0, p=0.32), and there was no significant trend in change of the calculated glomerular filtration rate (eGFR) from entry to follow-up (McNemar S=2.6, p=0.11).In the 161 patients with 3 and 6 month follow-up, taking mean 67,000 and median 50,000 IU of vitamin D3/week, median entry serum vitamin D rose from 21 to 42 to 44 ng/ml (p<0.0001), serum vitamin D was high (>100 but <150 ng/ml) in 2 patients at 3 months (1.2%, 101, 102 mg/ml) and in 3 (1.9%) at 6 months (101, 140, 140 ng/ml). Median serum calcium was unchanged from entry (9.7 mg/dl), at 3 and 6 months (9.7, 9.6 mg/dl, p>0.05). On vitamin D supplementation, the change in serum calcium from normal-to-high or high-to-normal was no significant trend (McNemar S=0.7, p=0.41), and no trend in change of eGFR (McNemar S=1.3, p=0.26).In the 58 patients with 3, 6, and 9 month follow-up on mean and median 71,000 and 100,000 IU of D3/week, median entry vitamin D rose from 20 to 37, 41, and 44 ng/ml (p<0.0001), with 1 (1.7%, 102 ng/ml), 2 (3.5%, 140, 140 ng/ml), and 0 (0%) patients high. Median serum calcium was unchanged from entry, median 9.7, 9.8, 9.6, and 9.6 mg/dl. On vitamin D supplementation, the trend of change in serum calcium from normal-to-high or high-to-normal was not significant (McNemar S=1.8, p=0.18), and no trend in change of eGFR (McNemar S=2, p=0.16).In the 22 patients with follow-up at 3, 6, 9, and 12 months on mean and median 70,000 and 75,000 IU of D3/week, median serum vitamin D rose from 20 to 37, to 41, to 44, and to 43 ng/ml (p<0.0001), with 1 (5%, 102 ng/ml) high, 2 (9%, 140, 140) high, 0 (0%) high, and 1 (5%, 126 ng/ml) high. Serum calcium was unchanged, median at entry 9.6, and then at 3, 6, 9, and 12 months 9.7, 9.7, 9.5, and 9.7 mg/ml. At entry serum calcium was normal in 21, none high, and one became high at 12 month follow-up. The trend of change in eGFR was insignificant, McNemar S=1.0, p=0.32.When serum D rose above 100 ng/ml in the few cases, as above, it fell into the normal range within 2 weeks by reducing the vitamin D dose by 50%.ConclusionsWhen 50,000–100,000 units of vitamin D/week are given to reverse statin intolerance in statin intolerant patients with low entry vitamin D (<32 ng/ml), it appears to be safe over up to 1 year follow-up, without toxic high serum vitamin D levels >150 ng/ml, and levels rarely >100 ng/ml, and without changes in serum calcium or eGFR.


2020 ◽  
Author(s):  
Han Zhang ◽  
Lian Lu ◽  
Wei Hu ◽  
Jian Zhang ◽  
Wei Zhu ◽  
...  

Abstract In order to identify the clinical characteristics of patients with Corona Virus Disease 2019 (COVID-19) and find out the characteristic effects of 2019 New Coronavirus (SARS-CoV-2) infection on changes in clinical and laboratory data, we analyzed the medical records of 80 suspected cases who admitted in the national designated hospital due to the relevant clinical manifestations of SARS-CoV-2 infection from January 22 to February 13, 2020. 62 (77.5%) confirmed cases and 18 (22.5%) negative cases were confirmed by SARS-CoV-2 nucleic acid test. Epidemiological investigation and statistical analysis were carried out on the clinical and laboratory data of all suspected cases of COVID-19, the specific indicators were found, and the clinical characteristics of COVID-19 were described. Compared with the patients with negative nucleic acid test, the patients with positive nucleic acid test showed shorter time of onset of symptoms, higher plasma CO2 level, lower eosinophil ratio, lower platelet count and hematocrit, lower serum sodium level, higher serum creatinine, higher blood urea and plasma albumin levels (all P<0.05). Our results might provide some suggestions in diagnosis, clinical treatment and prevention for COVID-19.


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Maimoona Bahlol ◽  
Alan Scott Sacerdote ◽  
Gul Bahtiyar

Abstract •Our patient is a 63-year-old African American female with medical history significant for hypertension, class 1 obesity, osteoarthritis of knees who initially presented to the adult ambulatory clinic on 9/19/2013 with complaints of body aches and bone pain. Labs were remarkable for a serum calcium level of 9.8 mg/dl, serum phosphorous of 4.7 mg/dl, and serum parathyroid hormone level of 166 pg/ml (15-65 pg/ml), normal GFR and serum vitamin 25-OH D of 62. A DEXA scan was performed which showed mild osteopenia wof 1.0 (0.8-1.8), serum 1,25 - OH vitamin D of &lt;8 pg/ml, normal alpha and beta carotene level, negative endomysial antibodies and normal magnesium level. A diagnosis of secondary hyperparathyroidism with unclear etiology was made. Same treatment was continued and a follow up in 3 months with repeat labs was advised. Repeat PTH went up to 281pg/ml but serum calcium and phosphate remained normal. Based on normal serum 25 OH vitamin D and low 1, 25 OH vitamin D, patient was started on calcitriol 0.25 mg daily. On next follow up in 3 months PTH decreased to 203pg/ml and 1, 25 OH vitamin D level normalized (35pg/ml). MEN was excluded with normal serum free metanephrine and gastrin levels. On subsequent visits DEXA scan normalized and PTH further trended downward to 101.7 pg/ml. Patient was discharged from endocrine clinic back to the PCP. • •Patient continued to follow up in adult medicine clinic but calcitriol fall off of patient’s medication list likely due to an error. Patient was off of calcitriol for 6 months but continue to take calcium vitamin D.PTH trended up to 186pg/ml and then to 350pg/ml. A referral to endocrinology was made again and a parathyroid sestamibi scan was obtained which did not reveal any abnormal uptake. Serum calcium, phosphate, magnesium and vitamin OH 25 vitamin D remained normal. •Patient was started back on calcitriol 0.5 mg daily and PTH again started to trend downward. The last PTH was down to 82 on March 20th 2019 with normal serum calcium, phosphate, magnesium and eGFR. The final diagnosis was secondary hyperparathyroidism due to decrease 1 alpha hydroxylase activityith a T score of −1.5 at left forearm. A diagnosis of primary hyperparathyroidism was made by the PCP and patient was started on calcium vitamin D and Fosamax and was referred to endocrinology for further evaluation. • •Further testing in the endocrine clinic revealed 24-hour urine calcium of 49 mg (100-300) and urine creatinine. This case report concludes that low 1-alpha hydroxylase activity should be considered as a cause of secondary hyperparathyroidism in a patient with normal GFR and 25-OH vitamin D level


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