DescriptorName: Hemochromatosis... AbstractText: Hereditary hemochromatosis can be divided into HFE- and non-HFE-related based ... Finally, the patient was diagnosed as ferroportin disease (type 4B hemochromatosis) AbstractText: The present study is the first report to identify ... classical splicing mutation in the SLC40A1 gene in type 4B hemochromatosis, and provide further evidence of the prevalence of type 4 hereditary hemochromatosis in Asian countries ...
Endocrine Disorders (1) Hemochromatosis (9), Iron Overload (2), Fibrosis (1), more mentions
AbstractText: To examine the magnetic resonance imaging (MRI) features of the ankle and subtalar joints that might distinguish genetic haemochromatosis (GH) AbstractText: The present study was a retrospective case-control study comparing 30 MRI studies of GH patients with ankle or subtalar arthropathy with 30 matched controls with ankle pain.
Muscular and Skeletal Diseases (1) Osteophyte (4), Cysts (2), Subchondral Cysts (1), more mentions
RATIONALE: Saccharated ferric oxide has been shown to lead to elevation of fibroblast growth factor 23, hypophosphatemia, and, consequently, osteomalacia. Moreover, mineral imbalance is often observed in patients with short-bowel syndrome to some degree.
PATIENT CONCERNS: A 62-year-old woman with short-bowel syndrome related with multiple resections of small intestines due to Crohn disease received regular intravenous administration of saccharated ferric oxide. Over the course of treatment, she was diagnosed with tetany, which was attributed to hypocalcemia. Additional assessments of the patient revealed not only hypocalcemia, but also hypophosphatemia, hypomagnesemia, osteomalacia, and a high concentration of fibroblast growth factor 23 (314 pg/mL).
DIAGNOSES: We diagnosed her with mineral imbalance-induced osteomalacia due to saccharated ferric oxide and short-bowel syndrome.
INTERVENTIONS: Magnesium replacement therapy and discontinuation of saccharated ferric oxide alone.
OUTCOMES: These treatments were able to normalize her serum mineral levels and increase her bone mineral density.
LESSONS: This case suggests that adequate evaluation of serum minerals, including phosphate and magnesium, during saccharated ferric oxide administration may be necessary, especially in patients with short-bowel syndrome.
Muscular and Skeletal Diseases (1) Osteomalacia (5), Hypocalcemia (3), Hypophosphatemia (3), more mentions
Hereditary hemochromatosis (HH) is a genetic disorder of iron metabolism which may lead to iron overload. Clinical penetrance is low, however those afflicted may develop cirrhosis, hepatocellular carcinoma, diabetes mellitus and cardiomyopathy. Treatment involves regular phlebotomy to reduce the systemic iron burden. In many countries-including the United States-numerous blood centers do not accept donated blood obtained from HH ...
Hypokalaemic periodic paralysis typically presents with intermittent mild-to-moderate weakness lasting hours to days. We report a case with an uncommon phenotype of late-onset myopathy without episodic paralytic attacks. Initial work-up including muscle biopsy was inconclusive. A subsequent review of the right deltoid biopsy, long exercise testing and repeated family history was helpful, followed by appropriate genetic testing. We identified a heterozygous pathogenic mutation in calcium ion channel (CACNA1S:c.1583G>A p.Arg528His) causing hypokalaemic periodic paralysis. Myopathy can present without episodic paralysis and the frequency of paralytic episodes does not correlate well with the development and progression of a fixed myopathy. Our report also highlights the intrafamilial phenotypic variation of hypokalaemic periodic paralysis secondary to a CACNA1S gene mutation.
BACKGROUND: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by severe hypophosphatemia and osteomalacia. Nonspecific symptoms make the diagnosis elusive. In addition, locating the responsible tumor(s) is challenging. The aim of this study was to investigate the clinical management and outcomes of TIO.
METHODS: The clinical features, diagnostic procedures, treatment, and outcomes of 12 patients were reviewed retrospectively.
RESULTS: The cohort comprised six men and six women (mean age 45.5 ± 9.9 years, range 23-61 years). The mean duration of disease was 3.7 ± 2.6 years. All patients manifested progressive bone pain, muscle weakness, and/or difficulty walking. Serum phosphorus concentrations were low in all patients (mean 0.42 ± 0.12 mmol/L). Technetium-99m octreotide scintigraphy was performed in 11 patients and showed lesions in the right distal femur, left femoral head, and right tibial plateau, respectively, in three patients. Magnetic resonance imaging (MRI) was negative for lesions in one patient. Two patients underwent biopsies that showed negative histopathology. Two patients, at 2 years and 8 months, respectively, after having negative technetium-99m octreotide studies, underwent (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (CT), which revealed lesions in the sacrum and soft tissue of the left palm, respectively. One tumor was detected by CT and MRI. Overall, lesion sites were the head (two patients, 16.7%), thoracic and lumbar region (two, 16.7%), pelvis (three, 25%), lower limbs (four, 33.3%), and upper limbs (one, 8.3%). All patients underwent surgery, and histopathology showed phosphaturic mesenchymal tumors in each. Postoperatively, serum phosphorus concentrations normalized within 2-7 days in 11 patients. With follow-ups of 1-41 months, surgery was effective in 10 patients. One patient developed local recurrence and another had metastases.
CONCLUSIONS: Locating tumors responsible for tumor-induced osteomalacia is often challenging. Although complete tumor resection confers a good prognosis in most patients, surveillance for recurrence and metastasis is necessary. Before surgery or when surgery is not indicated, oral phosphate can alleviate symptoms and metabolic imbalance.
Oncology (1) Neoplasms (9), Osteomalacia (4), Hypophosphatemia (1), more mentions
... RCMs will be presented followed by a detailed discussion on 3 major causes of RCM, for which tailored interventions are available: cardiac amyloidosis, cardiac sarcoidosis, and cardiac hemochromatosis... Clinical clues to promote recognition of cardiac amyloidosis, cardiac sarcoidosis, and cardiac hemochromatosis and imaging techniques used to facilitate diagnosis are discussed.
Cardiomyopathies (4), Sarcoidosis (2), Hemochromatosis (2), more mentions
BACKGROUND: Hypophosphatasia is a rare heritable metabolic disorder characterized by defective bone and tooth mineralization accompanied by a deficiency of tissue-non-specific (liver/bone/kidney) isoenzyme of alkaline phosphatase activity, caused by a number of loss-of-function mutations in the alkaline phosphatase liver type gene. We seek to explore the clinical manifestations and identify the mutations associated with the disease in a Chinese odonto- hypophosphatasia family.
RESULTS: The proband and his younger brother affected with premature loss of primary teeth at their 2-year-old. They have mild abnormal serum alkaline phosphatase and 25-hydroxy vitamin D values, but the serum alkaline phosphatase activity of their father, mother and grandmother, who showed no clinical symptoms of hypophosphatasia, was exhibited significant decreased. In addition to premature loss of primary teeth, the proband and his younger brother showed low bone mineral density, X-rays showed that they had slight metaphyseal osteoporosis changes, but no additional skeletal abnormalities. Deoxyribonucleic acid sequencing and analysis revealed a single nucleotide polymorphism c.787T>C (p.Y263H) in exon 7 and/or a novel mutation c.-92C>T located at 5'UTR were found in the affected individuals.
MATERIALS AND METHODS: We examined all individuals of an odonto- hypophosphatasia family by clinical and radiographic examinations as well as laboratory assays. Furthermore, all 12 exons and the exon-intron boundaries of the alkaline phosphatase liver type gene were amplified and directly sequenced for further analysis and screened for mutations.
CONCLUSION: Our present findings suggest the single nucleotide polymorphism c.787T>C and c.-92C>T should be responsible for the odonto- hypophosphatasia disorders in this family.
Muscular and Skeletal Diseases (2) Hypophosphatasia (5), Osteoporosis (1), more mentions
BACKGROUND: Pseudohypoparathyroidism (PHP) is caused by mutations and epimutations in the GNAS locus, and characterized by the possibility of resistance to multiple hormones and Albright's hereditary osteodystrophy. PHP can be classified into the forms 1A/C, sporadic 1B, and familial 1B.
OBJECTIVES: To obtain an overall view of the clinical and genetic characteristics of the Chinese PHP patient population.
METHODS: From 2000 to 2016, 120 patients were recruited and studied using Sanger sequencing, methylation-specific multiple ligation-dependent probe amplification (MS-MLPA), and combined bisulfiterestriction analysis (COBRA). Of these patients, 104 had positive molecular alterations indicative of certain forms of PHP and were included in data analysis. Clinical and laboratory features were compared between PHP1A/C and PHP1B patients.
RESULTS: Ten PHP1A/C, 21 familial PHP1B, and 73 sporadic PHP1B patients were identified. Four novel GNAS mutations were discovered in these patients, including c.1038+1G>T, c.530+2T>C, c.880_883delCAAG, and c.311_312delAAG,insT. The most common symptoms in this series were recurrent tetany (89.4%) and epilepsy (47.1%). The prevalence of weight excess increased with age for PHP1B (10-35%) and PHP1A/C (50-75%). Intracranial calcification had a prevalence of 94.6% and correlated with seizures (r=0.227, p=0.029). Cataracts occurred in 56.2% PHP patients, and there was a trend towards longer disease duration in patients with cataracts (p=0.051). Statistically significant differences (p<0.05) were observed when comparing certain clinical characteristics between PHP1B and PHP1A/C patients, including age of onset (10yr vs. 7yr), short stature (21.3 vs. 70%), rounded face (60.6 vs. 100%), brachydactyly (25.5 vs. 100%), ectopic ossification (1.1 vs. 40%), and TSH resistance (44.6 vs. 90%), respectively.
CONCLUSIONS: This study is the largest single-centre series of PHP patients and summarises the clinical and genetic features of the Chinese PHP population. While there was substantial clinical overlap between PHP1A/C and PHP1B, differences in disease progression were observed. This article is protected by copyright. All rights reserved.
Neurological and Central Nervous System Diseases (1) Pseudohypoparathyroidism (3), Cataract (2), Epilepsy (1), more mentions
BACKGROUND: The liver-synthesized peptide hepcidin is a key regulator of iron metabolism and correlates with total iron stores. We analyzed the association between pre-transplant hepcidin-25 levels and infection after kidney transplantation (KT).
METHODS: Serum hepcidin-25 levels were measured at baseline by high-sensitivity ELISA in 91 patients undergoing KT at our institution between December 2011 and March 2013. The impact of this biomarker on the incidence of post-transplant infection (excluding lower urinary tract infection) during the first year was assessed by Cox regression.
RESULTS: Mean hepcidin-25 level was 82.3 ± 67.4 ng/mL and strongly correlated with serum ferritin (Spearman's rho = 0.703; P <.001). There were no significant differences in hepcidin-25 levels between patients with or without overall infection (96.4 ± 67.5 vs 72.6 ± 66.7 ng/mL; P = .101). Such difference was evident for opportunistic (128.9 ± 75.0 vs 73.0 ± 62.3 ng/mL; P =.003) and, to a lesser extent, surgical-site infection (107.5 ± 73.3 vs 76.5 ± 65.2 ng/mL; P = .087). Patients with hepcidin-25 levels ≥72.5 ng/mL had higher 12-month cumulative incidence of overall infection (51.2% vs 29.2%; P = .032). After multivariate adjustment hepcidin-25 ≥72.5 ng/mL acted as an independent risk factor for overall (adjusted hazard ratio [aHR]: 3.86; 95% confidence interval [CI]: 1.49-9.96; P = .005) and opportunistic infection (aHR: 4.32; 95% CI: 1.18-15.75; P = .027).
CONCLUSION: Elevated baseline serum hepcidin-25 levels were associated with increased risk of infection after KT, suggesting a role for iron overload in the individual susceptibility to post-transplant infection. This article is protected by copyright. All rights reserved.
Urology (1) Infections (9), Iron Overload (3), Urinary Tract Infections (1), more mentions
This systematic review aims to assess the occurrence and risks of osteopenia and osteoporosis in patientswith Wilson's disease (WD). A literature search was conducted utilizing EMBASE and MEDLINE frominception through April 2017. Studies assessing the occurrence or risk of osteopenia and/or osteoporosis inWD patients were included. Effect estimates from the individual study were extracted and combined usingrandom-effect, generic inverse variance method of DerSimonian and Laird. Of 754 studies, four studies with283 WD patients met the eligibility criteria and were included in the data analysis. The pooled prevalencerates of osteopenia and osteoporosis in WD patients were 36.5% (95% confidence interval [CI]: 14.8%-65.7%) and 27.7% (95%CI: 8.6%-60.9%), respectively. When meta-analysis was limited only to adults, the estimated prevalence rates of osteopenia, osteoporosis, and vertebral fracture were 50.0% (95%CI: 42.0%-58.0%), 17.6% (95%CI: 6.7%-38.6%) and 8.01% (95%CI: 4.05%-15.2%), respectively. Meta-regressionshowed significant impacts of age (negative correlation; P=0.002) and male status (positive correlation;P < 0.001) on the prevalence of osteoporosis. The data on risks of osteopenia and osteoporosis in WDpatients were limited. We suggests that there are potential associations of WD with osteopenia and/orosteoporosis. Also, young age and male status are correlated with the higher prevalence of osteoporosis inWD patients.
Muscular and Skeletal Diseases (11) Osteoporosis (9), Osteopenia (7), Hepatolenticular Degeneration (3), more mentions
BACKGROUND & AIMS: Hepatic iron overload is associated with liver injury and hepatocarcinogenesis; however, it has not been evaluated in patients with hepatocellular carcinoma (HCC) in Asia. The aim of this study was to clarify the degree and distribution of intrahepatic iron deposition, and their effects on the survival of HCC patients.
METHODS: Intrahepatic iron deposition was examined using non-tumorous liver tissues from 204 HCC patients after curative resection, and they were scored by 2 semi-quantitative methods: simplified Scheuer's and modified Deugnier's methods. For the Scheuer's method, iron deposition in hepatocytes and Kupffer cells was separately evaluated, while for the modified Deugnier's method, hepatocyte iron score (HIS), sinusoidal iron score (SIS) and portal iron score (PIS) were systematically evaluated, and the corrected total iron score (cTIS) was calculated by multiplying the sum (TIS) of the HIS, SIS, and PIS by the coefficient.
RESULTS: The overall prevalence of hepatic iron was 40.7% with the simplified Scheuer's method and 45.1% with the modified Deugnier's method with a mean cTIS score of 2.46. During a median follow-up of 67 months, the cTIS was not associated with overall survival. However, a positive PIS was significantly associated with a lower 5-year overall survival rate (50.0%) compared with a negative PIS (73.7%, P = .006). In the multivariate analysis, a positive PIS was an independent factor for overall mortality (hazard ratio, 2.310; 95% confidence interval, 1.181-4.517).
CONCLUSIONS: Intrahepatic iron deposition was common, and iron overload in the portal tract indicated poor survival in curatively resected HCC patients.
Infectious Diseases (1) Iron Overload (4), Hepatocellular Carcinoma (3), Chronic Hepatitis B (1), more mentions
Acute liver failure secondary to acetaminophen overdose can be a life-threatening condition, characterized by severe electrolyte derangements. Hepatocyte regeneration is associated with phosphorous utilization and is a known complication of liver recovery following injury. We report the case of profound, life-threatening hypophosphatemia following recovery from acute fulminant liver failure. As the liver enzymes normalized, serum phosphorous levels plummeted. Our patient required an aggressive, individualized phosphorus replacement regimen, which resulted in a continuous infusion of intravenous (IV) sodium phosphate, titrated to a maximum rate of 30 mmol/h or 0.5 mmol/kg/h. The patient required over 400 mmol of total IV and oral phosphorous over the course of 48 hours. An aggressive approach to phosphorous replacement was done safely and effectively. Traditional replacement protocols are not adequate to sustain patients with this degree of hypophosphatemia. This is the first report to utilize a continuous infusion of phosphate with a maximum reported rate (0.5 mmol/kg/h). Our report summarizes a novel and safe approach for clinicians to maximally support these patients through high-dose, continuous infusion phosphorous administration.