The First Case of Caroli Disease Presented as Diabetes and Gastric Perforation

Caroli disease is a rare autosomal recessive disorder with cystic changes in liver, kidney and pancreas. It is a genetic disorder involving PKHD1 gene, encoding fibrocystin, often seen in liver and kidney. This is the first case reported with diabetes and gastric perforation. This 26 years old man presented as diabetes and abdominal pain, which worsened as gastric perforation. He also had enlarged spleen, cystic liver and kidney. His ALT and AST were normal, but GGT and bilirubin were elevated. None of hepatic virus related antigen is positive. No autoimmune hepatitis antibody was found. His blood glucose was high, with the hemoglobinA1c of 12.3% and reduced postprandial C peptide, but negative autoimmune diabetic antibodies. He has an 18 years old sister who was operated at 12 years old due to gastric bleeding and her spleen was removed. She was also diagnosed as Caroli disease. Neither his parents had similar presentation. As PKHD1 gene encodes fibrocystin, which may present at any conjunction. While fibrocystin tights up tissues, vessels and walls of the hollow organs, it is my belief that the cystic changes due to PKHD1 deletion or mutation can happen in any organ or vessel. This explains why this patient presented as diabetes and gastric perforation.

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The combination of cystic thyroid changes with cystic changes in other organs

Problems of Endocrinology ◽

10.14341/probl11369 ◽

1995 ◽

Vol 41 (2) ◽

pp. 27-27

Author(s):

E. V. Murahovskaya ◽

I. B. Katsova

Keyword(s):

Thyroid Gland ◽

Clinical Manifestation ◽

Thyroid Dysfunction ◽

Left Kidney ◽

Practical Interest ◽

Cystic Changes ◽

Liver And Kidney ◽

Thin Walled ◽

Cystic Liver ◽

Congenital Cysts

The combination of cystic changes in the thyroid gland with a violation of its function with cystic changes in other organs is rare and is of practical interest. Thyroid dysfunction can be due to various causes. In the literature, there are a small number of observations of a combination of cystic changes in a number of organs, including the thyroid gland. The literature describes the combination of congenital cysts of the lungs, kidneys, thyroid gland in a child of 11 months, who was diagnosed with polycystic left kidney and multiple thin-walled cavities in the lower pulmonary field. Left-sided nephrectomy was performed. In 3 years - left-sided hemistrumectomy for macrofollicular adenoma of the thyroid gland. In the dynamics of the patient there was an increase in the size of cysts in the lungs without clinical manifestation. In adults, such changes are not described. This article presents a case of cystic thyroid changes with hyperthyroidism combined with cystic liver and kidney changes.

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Anesthesia in Carvajal syndrome; the first case report

Anaesthesia, Pain & Intensive Care ◽

10.35975/apic.v24i1.1233 ◽

2020 ◽

Vol 24 (1) ◽

pp. 105-107

Author(s):

Sedighe Shahhosseini ◽

Reza Aminnejad ◽

Amir Shafa ◽

Mehrdad Memarzade

Keyword(s):

Intensive Care ◽

Case Report ◽

Surgical Resection ◽

Genetic Disorder ◽

Anesthetic Technique ◽

Close Monitoring ◽

Anesthesia Management ◽

Rare Genetic Disorder ◽

First Case ◽

Anesthetic Considerations

Carvajal syndrome is a rare genetic disorder. Patients reporting for surgery pose some difficulties in anesthesia management. In this case report we present the case of a 12-year-old boy, who was a known case of Carvajal syndrome, referred for surgical resection of perianal condyloma. Close monitoring of hemodynamic status is the mainstay of anesthetic considerations in such patients. As in any other challenging scenario, it should be kept in mind that ‘there is no safest anesthetic agent, nor the safest anesthetic technique; there is only the safest anesthesiologist’. Citation: Shahhosseini S, Aminnejad R, Shafa A, Memarzadeh M. Anesthesia in Carvajal syndrome; the first case report. Anaesth pain intensive care 2020;24(1):___ DOI: https://doi.org/10.35975/apic.v24i1.

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Primary Gastrointestinal Stromal Tumor of the Liver with Cystic Changes

Case Reports in Gastroenterology ◽

10.1159/000495604 ◽

2019 ◽

Vol 13 (1) ◽

pp. 58-65

Author(s):

Takashi Tashiro ◽

Fumihiro Uwamori ◽

Yukiomi Nakade ◽

Tadahisa Inoue ◽

Yuji Kobayashi ◽

...

Keyword(s):

Liver Tumors ◽

Past History ◽

Brain Infarction ◽

Arterial Phase ◽

First Case ◽

Positron Emission ◽

Cystic Changes ◽

Multiple Bone Metastases ◽

The Right ◽

Cells Of Cajal

Gastrointestinal stromal tumors (GISTs) are known to originate specifically from the intestinal cells of Cajal located in the gastrointestinal mesenchyme. GISTs developing outside of the digestive tract have barely been reported. We encountered a first case of large primary GISTs in the liver with cystic changes. A 63-year-old man with a past history of brain infarction visited our hospital. The computed tomography (CT) revealed a 6-cm and a 10-cm mass in the right and the caudal lobe of the liver, respectively. These tumors have marginal enhancement in the arterial phase; however, they presented as hypodense in the internal tumor sites. Both liver tumors had cystic changes. Gastrointestinal examinations using endoscopy revealed no other gastrointestinal tumors, and [18F]-fluoro-2-deoxy-D-glucose positron emission tomography/CT revealed multiple bone metastases in addition to the liver tumors. The liver tumor specimens were composed of spindle cells, and the immunohistochemical staining for c-Kit and for DOG1, as discovered on GIST, was positive. The patient was diagnosed with primary hepatic GIST with cystic changes.

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Novel mutations in the WFS1 gene are associated with Wolfram syndrome and systemic inflammation

Human Molecular Genetics ◽

10.1093/hmg/ddab040 ◽

2021 ◽

Author(s):

Eleonora Panfili ◽

Giada Mondanelli ◽

Ciriana Orabona ◽

Maria L Belladonna ◽

Marco Gargaro ◽

...

Keyword(s):

Er Stress ◽

Mononuclear Cells ◽

Autosomal Recessive Disorder ◽

Wolfram Syndrome ◽

Therapeutic Interventions ◽

T Helper 17 ◽

Gene Encoding ◽

Peripheral Blood Mononuclear ◽

Inflammatory State ◽

Wfs1 Gene

Abstract Mutations in the WFS1 gene, encoding wolframin (WFS1), cause endoplasmic reticulum (ER) stress and are associated with a rare autosomal-recessive disorder known as Wolfram syndrome (WS). WS is clinically characterized by childhood-onset diabetes mellitus, optic atrophy, deafness, diabetes insipidus and neurological signs. We identified two novel WFS1 mutations in a patient with WS, namely, c.316-1G > A (in intron 3) and c.757A > T (in exon 7). Both mutations, located in the N-terminal region of the protein, were predicted to generate a truncated and inactive form of WFS1. We found that although the WFS1 protein was not expressed in peripheral blood mononuclear cells (PBMCs) of the proband, no constitutive ER stress activation could be detected in those cells. In contrast, WS proband’s PBMCs produced very high levels of proinflammatory cytokines (i.e. TNF-α, IL-1β, and IL-6) in the absence of any stimulus. WFS1 silencing in PBMCs from control subjects by means of small RNA interference also induced a pronounced proinflammatory cytokine profile. The same cytokines were also significantly higher in sera from the WS patient as compared to matched healthy controls. Moreover, the chronic inflammatory state was associated with a dominance of proinflammatory T helper 17 (Th17)-type cells over regulatory T (Treg) lymphocytes in the WS PBMCs. The identification of a state of systemic chronic inflammation associated with WFS1 deficiency may pave the way to innovative and personalized therapeutic interventions in WS.

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Van Buchem Disease: First Case Report from the Indian Subcontinent with an Early Presentation

Journal of Child Science ◽

10.1055/s-0041-1723956 ◽

2021 ◽

Vol 11 (01) ◽

pp. e38-e41

Author(s):

Saurabh Maheshwari ◽

Sonam Yangzom ◽

K. Uday Bhanu ◽

Uddandam Rajesh ◽

Ashok Narayan

Keyword(s):

Western Europe ◽

Indian Subcontinent ◽

Genetic Disorder ◽

Rare Condition ◽

Bone Dysplasia ◽

Feedback Mechanism ◽

Early Presentation ◽

First Case ◽

Cranial Nerve Palsies ◽

Van Buchem Disease

AbstractVan Buchem disease is a rare autosomal recessive genetic disorder that causes a compromised inhibitory feedback mechanism resulting in increased bone formation and overgrowth of the skeleton leading to a variety of neurological symptoms. It has been reported in less than 50 patients most of which were in western Europe. We report the first case of this condition from the Indian subcontinent with an early presentation. This patient presented with a global delay in attaining the developmental milestones and progressive reduction in visual acuity and loss of hearing. He had dysmorphic facies, multiple cranial nerve palsies, and severe visual and auditory deficits. Imaging revealed sclerosing bone dysplasia. This case illustrates the clinical and imaging findings of this rare condition.

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Exclusive Neurogenic Bladder and Fecal Incontinency in an Achondroplasic Child Successfully Treated with Lumbar Foraminal Decompression

Pediatric Neurosurgery ◽

10.1159/000517652 ◽

2021 ◽

pp. 1-6

Author(s):

Flavio Giordano ◽

Matteo Lenge ◽

Pierarturo Donati ◽

Lorenzo Mongardi ◽

Gianpiero Di Giacomo ◽

...

Keyword(s):

Fecal Incontinence ◽

Neurogenic Bladder ◽

Genetic Disorder ◽

Motor Impairment ◽

Foramen Magnum ◽

Clinical Findings ◽

Lumbar Stenosis ◽

Endochondral Bone ◽

Case Presentation ◽

First Case

Introduction: Achondroplasia is a genetic disorder characterized by defects in the development of endochondral bone resulting in skeletal abnormalities like stenosis of the foramen magnum and of the spine, shortened limb bones, and macrocephaly. Congenital spinal stenosis is frequent and due to premature fusion of the pedicles to the laminae. Case Presentation: We report a case of neurogenic bladder and fecal incontinence due to lumbar stenosis successfully treated with L1–L5 partial laminectomy and foraminotomy in a 7-year-old achondroplasic child. Discussion/Conclusion: To our knowledge, this is the first case report of exclusive neurogenic bladder and fecal incontinence in an achondroplasic child. Neurogenic bladder and fecal incontinence without motor impairment may be early and exclusive clinical findings of lumbar stenosis in children with achondroplasia.

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A role for microRNA in cystic liver and kidney diseases

Journal of Clinical Investigation ◽

10.1172/jci36870 ◽

2008 ◽

Vol 118 (11) ◽

pp. 3585-3587 ◽

Cited By ~ 20

Author(s):

Andrew S. Chu ◽

Joshua R. Friedman

Keyword(s):

Kidney Diseases ◽

Liver And Kidney ◽

Cystic Liver

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Case Report: Recurrent Variant c.298 TA in CCN6 Gene Found in Progressive Pseudorheumatoid Dysplasia Patients From Patni Community of Gujarat: A Report of Three Cases

Frontiers in Genetics ◽

10.3389/fgene.2021.724824 ◽

2021 ◽

Vol 12 ◽

Author(s):

Harsh Sheth ◽

Jhanvi Shah ◽

Aadhira Nair ◽

Premal Naik ◽

Jayesh Sheth

Keyword(s):

Genetic Disorder ◽

Case Series ◽

Missense Variant ◽

Community Analysis ◽

Gait Disturbance ◽

Mutant Genotype ◽

Progressive Pseudorheumatoid Dysplasia ◽

First Case ◽

Abnormal Posture ◽

Biallelic Mutations

Biallelic mutations in the CCN6 gene are known to cause a rare genetic disorder—progressive pseudorheumatoid dysplasia (PPD). PPD is characterized by distinct joint deformities of interphalangeal joints, stiffness, gait disturbance, abnormal posture, and absence of inflammation, resulting in significant morbidity. The largest case series of PPD from India suggests c.233G>A and c.1010G>A to be the most common mutations in the CCN6 gene, although the distribution of these variants among endogamous communities in India has not been carried out. We here report three cases of PPD from three independent families belonging to the Patni community of Gujarat, a community known to practice endogamy. All three cases had short stature, gait disturbance, scoliosis, and interphalangeal joint deformities. Analysis by whole-exome sequencing in the first case showed the presence of a previously known, homozygous, missense variant c.298T>A (p.Cys100Ser) in exon 3 of the CCN6 gene in all cases. Due to all three families belonging to the same community, analysis by Sanger sequencing in the remaining two cases for the variant mentioned earlier showed both cases to be of homozygous mutant genotype. Unaffected family members, i.e., parents and siblings, were either heterozygous carriers or wildtype for the said variant. The present case series is the first report of a recurrent variant occurring across multiple PPD-affected individuals from unrelated families belonging to the same community from India.

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Two Monogenetic Disorders, Activated PI3-Kinase-δ Syndrome 2 and Smith–Magenis Syndrome, in One Patient: Case Report and a Literature Review of Neurodevelopmental Impact in Primary Immunodeficiencies Associated With Disturbed PI3K Signaling

Frontiers in Pediatrics ◽

10.3389/fped.2021.688022 ◽

2021 ◽

Vol 9 ◽

Author(s):

Nidia Moreno-Corona ◽

Loïc Chentout ◽

Lucie Poggi ◽

Romane Thouenon ◽

Cecile Masson ◽

...

Keyword(s):

Viral Infections ◽

Genetic Disorder ◽

Pi3 Kinase ◽

Pi3k Signaling ◽

Gene Encoding ◽

Regulatory Subunits ◽

Neurodevelopmental Delay ◽

Exon 11 ◽

Complex Genetic Disorder ◽

Splice Product

Activated PI3-kinase-δ syndrome 2 (APDS2) is caused by autosomal dominant mutations in the PIK3R1 gene encoding the p85α, p55α, and p50α regulatory subunits. Most diagnosed APDS2 patients carry mutations affecting either the splice donor or splice acceptor sites of exon 11 of the PIK3R1 gene responsible for an alternative splice product and a shortened protein. The clinical presentation of APDS2 patients is highly variable, ranging from mild to profound combined immunodeficiency features as massive lymphoproliferation, increased susceptibility to bacterial and viral infections, bronchiectasis, autoimmune manifestations, and occurrence of cancer. Non-immunological features such as growth retardation and neurodevelopmental delay have been reported for APDS2 patients. Here, we describe a patient suffering from an APDS2 associated with a Smith–Magenis syndrome (SMS), a complex genetic disorder affecting, among others, neurological manifestations and review the literature describing neurodevelopmental impacts in APDS2 and other PIDs/monogenetic disorders associated with dysregulated PI3K signaling.

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Identification and functional characterisation of a novel KCNJ2 mutation, Val302del, causing Andersen–Tawil syndrome

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2014-0527 ◽

2015 ◽

Vol 93 (7) ◽

pp. 569-575 ◽

Cited By ~ 2

Author(s):

Balázs Ördög ◽

Lidia Hategan ◽

Mária Kovács ◽

György Seprényi ◽

Zsófia Kohajda ◽

...

Keyword(s):

Membrane Trafficking ◽

Genetic Disorder ◽

Clinical Manifestations ◽

Clinical Importance ◽

Inhibitory Effect ◽

Periodic Paralysis ◽

Inward Rectification ◽

Loss Of Function ◽

Gene Encoding ◽

Functional Characterisation

Loss-of-function mutations of the KCNJ2 gene encoding for the inward rectifier potassium channel subunit Kir2.1 cause Andersen–Tawil Syndrome (ATS), a rare genetic disorder characterised by periodic paralysis, ventricular arrhythmias, and dysmorphic features. Clinical manifestations of the disease appear to vary greatly with the nature of mutation, therefore, functional characterisation of ATS-causing mutations is of clinical importance. In this study, we describe the identification and functional analysis of a novel KCNJ2 mutation, Val302del, identified in a patient with ATS. Heterologously expressed wild type (WT) and Val302del mutant alleles showed similar subcellular distribution of the Kir2.1 protein with high intensity labelling from the membrane region, demonstrating normal membrane trafficking of the Val302del Kir2.1 variant. Cells transfected with the WT allele displayed a robust current with strong inward rectification, while no current above background was detected in cells expressing the Val302del Kir2.1 subunit. Co-transfection of CHO cells with the WT and the Val302del Kir2.1 revealed a dose-dependent inhibitory effect of the Val302del Kir2.1 mutant subunit on WT Kir2.1 currents. These observations indicate that the WT and the Val302del mutant subunits co-assemble in the cell membrane and that the mutation affects potassium conductivity and (or) gating of the WT/Val302del heteromeric Kir2.1 channels.

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