Absence Of Biochemical Abnormalities Research Articles

Fahr's Disease Presenting with Pure Dementia: A Case Report and Literature Review

Fahr's disease (FD) is a rare inherited or sporadic disorder characterized by symmetrical calcium deposits in the basal ganglia and dentate nuclei with the absence of biochemical abnormalities. Clinical manifestations can start at different ages with a variety of presentations. We report a case of a 68-year-old male who presented to our service with clinical signs and symptoms of pure and progressive dementia. Afterward, he developed mood changes, and finally, movement disorders, probably due to a sporadic form of FD. Noncontrast cranial computed tomography scan demonstrated scattered brain parenchyma, bilateral calcifications in the basal ganglia, and dentate nuclei. Standard blood tests were within the normal limits. In this way, FD can present with pure dementia at onset, reflecting a wide range of neurological manifestations. The diagnosis is challenging, and we proposed an acronym to facilitate the learning of the diagnostic criteria.

Fahr’s Disease in a 26 year-old female: A case report

Background: Fahr’s disease is a rare, degenerative neurological-psychiatric disorder characterized by idiopathic symmetrical and bilateral intracranial calcification. Prevalence of <1:1,000,000, usually presents at middle age group, rarely in the young. Calcification are deposited in basal ganglia, thalamus, putamen, hippocampus, cerebral cortex, cerebellar subcortical white matter and dentate nucleus. Diagnosis requires certain clinical criteria: absence of biochemical abnormalities and somatic features; absence of infection, trauma, toxic cause; presence of progressive neuropsychiatric dysfunction with onset of symptoms at 4th – 5th decade of life, presence of bilateral basal ganglia calcification visualized on neuroimaging and family history with autosomal dominant inheritance or sporadic.

Fahr’s syndrome: literature review of current evidence

Fahr’s disease or Fahr’s syndrome is a rare, neurological disorder characterized by abnormal calcified deposits in basal ganglia and cerebral cortex. Calcified deposits are made up of calcium carbonate and calcium phosphate, and are commonly located in the Basal Ganglia, Thalamus, Hippocampus, Cerebral cortex, Cerebellar Subcortical white matter and Dentate Nucleus. Molecular genetics of this disease haven’t been studied extensively; hence evidence at the molecular and genetic level is limited. Fahr’s disease commonly affects young to middle aged adults. Etiology of this syndrome does not identify a specific agent but associations with a number of conditions have been noted; most common of which are endocrine disorders, mitochondrial myopathies, dermatological abnormalities and infectious diseases. Clinical manifestations of this disease incorporate a wide variety of symptoms, ranging from neurological symptoms of extrapyramidal system to neuropsychiatric abnormalities of memory and concentration to movement disorders including Parkinsonism, chorea and tremors amongst others. Diagnostic criteria for this disease has been formulated after modifications from previous evidence and can be stated briefly, it consist of bilateral calcification of basal ganglia, progressive neurologic dysfunction, absence of biochemical abnormalities, absence of an infectious, traumatic or toxic cause and a significant family history. Imaging modalities for the diagnosis include CT, MRI, and plain radiography of skull. Other investigations include blood and urine testing for hematologic and biochemical indices. Disease is as yet incurable but management and treatment strategies mainly focus on symptomatic relief and eradication of causative factors; however certain evidence is present to suggest that early diagnosis and treatment can reverse the calcification process leading to complete recovery of mental functions. Families with a known history of Fahr’s disease should be counseled prior to conception so that the birth of affected babies can be prevented. This review was written with the aim to remark on the current substantial evidence surrounding this disease.

Riedel’s Thyroiditis Occurring in a Multinodular Goiter, Mimicking Thyroid Cancer

A 52-yr-old female with multinodular goiter with benign fine-needle aspiration (FNA) cytology presented with progressive compressive symptoms. Clinically, the left lobe was enlarged, painless, but firm. Serum TSH and calcitonin were normal, and thyroglobulin was elevated. C-reactive protein and leukocyte counts were normal. Thyroid-related autoantibodies (thyroid peroxidase, thyroglobulin, and TSH receptor) were absent. The ultrasound performed 1 yr before showed hyperechoic nodules (Fig. 1A). Now, the volume of the left lobe increased nearly 2-fold due to hypoechoic, hypovascular tissue surrounding the hyperechoic nodules (Fig. 1B). During FNA, the hypoechoic tissue felt remarkably harder than the hyperechoic nodules. Cytology of the nodules was confirmed to be benign. However, cytology of the hypoechoic part showed a small amount of follicular epithelial cells with enlarged, irregular nuclei and no colloid. Based on the inconclusive cytology, the absence of biochemical abnormalities, and the increasing mechanical complaints, a total thyroidectomy was performed. During surgery, a white stony-hard left thyroid lobe was disclosed. Histopathologic examination showed a sclerotic mass, consisting of spindle-shaped cells and mononuclear inflammatory cells, infiltrating the follicular adenomas (Fig. 2), leading to the diagnosis of Riedel’s thyroiditis. This is a rare fibrosclerotic infiltrative thyroid disorder of unclear etiology, during which normal thyroid tissue is replaced by fibrous tissue, hypoechoic and hypovascular on ultrasound (2, 3), often expanding outside the thyroid capsule, and sometimes part of multifocal (retroperitoneal, retroorbital, and mediastinal) fibrosclerosis (1–3). The main differential diagnosis is invasive thyroid cancer. FNA often fails to dis-

Novel GALNT3 Mutations Causing Hyperostosis-Hyperphosphatemia Syndrome Result in Low Intact Fibroblast Growth Factor 23 Concentrations

Hyperostosis-hyperphosphatemia syndrome (HHS) is a rare metabolic disorder characterized by hyperphosphatemia and localized hyperostosis. HHS is caused by mutations in GALNT3, which encodes UDP-N-acetyl-alpha-D-galactosamine:polypeptide N- acetylgalactosaminyltransferase 3. Familial tumoral calcinosis (TC), characterized by ectopic calcifications and hyperphosphatemia, is caused by mutations in the GALNT3 or fibroblast growth factor 23 (FGF23) genes. Our objective was to identify mutations in FGF23 or GALNT3 and determine serum FGF23 levels in an HHS patient. Mutation detection in FGF23 and GALNT3 was performed by DNA sequencing, and serum FGF23 concentrations were measured by ELISA. A 5-year-old French boy with HHS and his family members participated. The patient presented with painful cortical lesions in his leg. Radiographs of the affected bone showed diaphyseal hyperostosis. The lesional tissue comprised trabeculae of immature, woven bone surrounded by fibrous tissue. Biochemistry revealed elevated phosphate, tubular maximum rate for phosphate reabsorption per deciliter of glomerular filtrate, and 1,25-dihydroxyvitamin D levels. The patient was a compound heterozygote for two novel GALNT3 mutations. His parents and brother were heterozygous for one of the mutations and had no biochemical abnormalities. Intact FGF23 level in the patient was low normal, whereas C-terminal FGF23 was elevated, a pattern similar to TC. The presence of GALNT3 mutations and elevated C-terminal, but low intact serum FGF23, levels in HHS resemble those seen in TC, suggesting that HHS and TC are different manifestations of the same disorder. The absence of biochemical abnormalities in the heterozygous individuals suggests that one normal allele is sufficient for secretion of intact FGF23.

Histologic activity of childhood chronic hepatitis B related to viremia levels, genotypes, mutations, and epidemiologic factors.

Despite high viral load, children with chronic hepatitis B virus (HBV) infection may lack significant biochemical signs of liver dysfunction. Failure to develop abnormal liver chemistriesis is probably due to immunologic hyporeactivity. Despite the absence of biochemical abnormalities in these patients, there is still a risk for long-term complications. The pathogenic importance of viral load and genetic variability is less well studied in children than in adults. We evaluated viremia levels, genotypes, and mutations related to histologic evidence of liver damage in 71 HBV carriers, aged 2 to 18 years, all of non-Swedish origin. None of the of 22 children who were hepatitis B e antigen (HBeAg) negative had severe liver disease or had HBV DNA levels greater than 10 copies/mL (mean 10 ); 3 (14%) of them had increased alanine aminotransferase (ALT). The 49 HBeAg-positive children had a mean HBV DNA level of 10 copies/mL, and increased ALT was seen in 28 (55%). Core promoter mutations (at nt 1764) or precore mutations (at codon 1, 2, or 28) were rare; they were seen in four and one HBeAg-positive children, and in four and nine HBeAg-negative children, respectively, without association to liver damage. C-1858 was associated with more liver inflammation. Genotype did not significantly influence liver damage. Children with horizontal transmission had a faster rate of seroconversion and more inflammation of the liver. Severe HBeAg-negative hepatitis with high HBV DNA levels and mutations in the core promoter or precore regions seems to be less common in children than in adults. C-1858 strains may be more pathogenic, but this requires further study. Epidemiologic factors influence the course of infection.

Thymoglobulin induction decreases rejection in solitary pancreas transplantation.

Solitary pancreas transplants, both pancreas transplant alone (PTA) and pancreas after kidney (PAK), have higher rejection rates and lower graft survivals than simultaneous pancreas-kidney transplants (SPK). The aim of this study is to compare three different antibody induction regimens in solitary pancreas transplant recipients and to assess the role of surveillance pancreas biopsies in the management of these patients. Solitary pancreas transplant recipients between 01/98 to 02/00 (n=29) received induction with either daclizumab (1 mg/kg on day 0, 7, 14), OKT 3 (5 mg/day x0-7), or thymoglobulin (1.5 mg/kg/day x0-10). Maintenance immunosuppression was similar for the three groups. All rejections were biopsy-proven either by surveillance/protocol or when clinically indicated. The 1-year graft survival was 89.3% overall and 91.7% in the thymoglobulin group. Thymoglobulin significantly decreased rejection in the first 6 months when compared with OKT3 or daclizumab (7.7 vs. 60 vs. 50%). Acute rejections were seen on surveillance biopsies in the absence of biochemical abnormalities in 40% of patients. Thymoglobulin induction regimen led to a low incidence of acute rejection and a high rate of graft survival in solitary pancreas transplants. In addition, surveillance biopsies were useful in the detection of early acute rejection in the absence of biochemical abnormalities.

RDCI, the vasoactive intestinal peptide receptor: a candidate gene for the features of Albright hereditary osteodystrophy associated with deletion of 2q37.

Albright hereditary osteodystrophy (AHO) is an autosomal dominant disorder characterised by the presence of brachymetaphalangism, short stature, obesity, and mental retardation. Variable biochemical changes many represent either pseudohypoparathyroidism (PHP) owing...

Prospective study of clinical and biochemical features of symptomatic choledocholithiasis.

One hundred consecutive patients were prospectively studied to assess the clinical and biochemical features of symptomatic choledocholithiasis. Biochemical tests were performed during the three days following the onset of symptoms. Pain was the most frequent symptom of choledocholithiasis, observed in 75% of the patients, but rarely occurred alone (12%). Clinical symptoms were not different according to age. High serum gamma glutamyl transpeptidase and alkaline phosphatase were the most frequent biochemical abnormalities in patients with symptomatic choledocholithiasis: they were increased in 94 and 91% of cases, respectively. Only one patient had no biochemical abnormality. Serum transaminases could reach very high levels just as in hepatitis. Biochemical data did not differ regardless of whether the common bile duct was enlarged or not. Biochemical abnormalities had been studied over the first 10 days of spontaneous evolution in 25 patients while choledocholithiasis persisted: serum bilirubin and transaminases significantly decreased while serum gamma glutamyl transpeptidase, alkaline phosphatase, and amylase remained unchanged. These results indicate that, in patients with suggestive symptoms, choledocholithiasis is unlikely in the absence of biochemical abnormalities in the first three days following the onset of symptoms.