Clinical findings in five Turkish patients with citrin deficiency and identification of a novel mutation on SLC25A13

AbstractBackgroundCitrin deficiency (CD) is an autosomal recessive genetic disorder caused by a defect in the mitochondrial aspartate/glutamate antiporter, citrin. Three clinical manifestations have been described until today.Case presentationWe reported 5 CD patients from two families. Four patients were male and one patient was female. Two of them have NICCD (neonatal intrahepatic cholestasis caused by citrin deficiency); three of them have CTLN2 (adult-onset type II citrullinemia). Both NICCD patients showed typical clinical and biochemical changes with a diagnosis confirmed by mutations in the SLC25A13 gene. We detected a previously unreported homozygous novel mutation c.478delC (L160Wfs*36 ) on the SLC25A13 gene. All of the CTLN2 patients were siblings. Proband was a 15-year-old mentally retarded and autistic male who had admitted to our emergency with disorientation. Laboratory data showed hyperammonemia and citrullinemia.ConclusionsTwo different profiles of age-related CD have been depicted with this article. It has been aimed to underline that the CD can be observed in different forms not only in neonatals or little infants but also in adolescents. This article is the first case series that covers both NICCD and CTLN2 cases together and that has been published in Turkey. Considering the fact that especially the majority of CTLN2 cases have been identified in Asian countries, our article has vital importance in terms of defining phenotypic features of the disease.

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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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Case Series : Operative vs Non-Operative Management in Grade III Pancreatic Injury

Medicinus ◽

10.19166/med.v7i6.2598 ◽

2020 ◽

Vol 7 (6) ◽

pp. 199

Author(s):

Andry Irawan ◽

Clinton Clinton ◽

Sutanto D ◽

Agustina F

Keyword(s):

Case Series ◽

Operative Management ◽

Pancreatic Injury ◽

Clinical Findings ◽

First Case ◽

Non Operative Management ◽

Left Abdomen ◽

Grade Iii ◽

Selection Of

Introduction: Pancreatic injury is a rare case, caused by blunt or sharp trauma. Difficulty in making diagnose on pancreatic trauma cases are associated with high mortality, and the treatment can be either operative or conservatively. However, It is still unclear which treatment is more favorable.Case: We present 2 cases of Grade III pancreatic injury with stable hemodynamic who suffered bicycle accident. First case, 12-year-old boy complaining severe pain on the upper left abdomen (VAS 9-10) and get worsening by time, with vomiting. The patient underwent distal Pancreatectomy-Splenectomy. Second case, 8-year-old boy complaining of pain on the upper left abdomen (VAS 6-7) without extension on whole abdominal region with vomiting and fever. The patient was treated conservatively. In both cases, patient was discharged with improvement. However, about 3 months later patients who were treated conservatively developed into a pseudocyst.Conclusion: The selection of management in grade III pancreatic injury can be operative or conservative depending on clinical findings such as hemodynamic condition and the quality of abdominal pain. But the occurrence of pseudocysts pancreas is another surgical challenge.

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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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Spectrum of Ankyrin Mutations in Hereditary Spherocytosis: A Case Report and Review of the Literature

Acta Haematologica ◽

10.1159/000492024 ◽

2018 ◽

Vol 140 (2) ◽

pp. 77-86 ◽

Cited By ~ 1

Author(s):

Yeping Luo ◽

Zhuoying Li ◽

Lihua Huang ◽

Jing Tian ◽

Menglong Xiong ◽

...

Keyword(s):

Hereditary Spherocytosis ◽

Novel Mutation ◽

Laboratory Data ◽

Clinical Manifestations ◽

Mutation Spectrum ◽

Chinese Family ◽

Review Of The Literature ◽

Newborn Period ◽

Gene Splicing ◽

Generation Sequencing

Background/Aims: Hereditary spherocytosis (HS) is a common pediatric hemolytic anemia caused by congenital red blood cell defects. HS due to ankyrin 1 (ANK1) mutations is the most common type. We explored an ANK1 mutation from an HS patient and reviewed the literature. Methods: We detected the mutation in a Chinese family in which 2 members were diagnosed with HS by next-generation sequencing. The proband was diagnosed with HS in the newborn period, based on clinical manifestations, laboratory data, and family history. The mutation spectrum of the ANK1 gene was summarized based on 85 patients diagnosed with HS carrying ANK1 mutations, and the ANK1 mutation spectrum was summarized and analyzed. Results: We identified a novel mutation affecting ANK1 gene splicing (a splicing mutation) in both the patient and her mother, which is a substitution of T>G 2 nt after exon 25 in intron 26. The study expands our knowledge of the ANK1 gene mutation spectrum, providing a molecular basis for HS. Conclusion: A novel ANK1 mutation (NM_000037.3, c.2960+2T>G, intron 26) that is potentially associated with HS was identified. To date, 80 ANK1 mutations have been reported to be associated with HS in humans.

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Relentless Placoid Chorioretinitis: A Case Series of Successful Tapering of Systemic Immunosuppressants Achieved with Adalimumab

Case Reports in Ophthalmology ◽

10.1159/000500077 ◽

2019 ◽

Vol 10 (1) ◽

pp. 145-152 ◽

Cited By ~ 1

Author(s):

Shotaro Asano ◽

Rie Tanaka ◽

Hidetoshi Kawashima ◽

Toshikatsu Kaburaki

Keyword(s):

Immunosuppressive Agents ◽

Case Series ◽

Clinical Findings ◽

Posterior Pole ◽

Peripheral Retina ◽

Conjunctival Hyperemia ◽

Systemic Corticosteroids ◽

First Case ◽

Adalimumab Therapy ◽

Relentless Placoid Chorioretinitis

Background: Adalimumab, a human anti-tumor necrosis factor-ɑ monoclonal antibody, was recently reported to be effective in lowering the risk of recurrence of noninfectious uveitis. This is the first case series of adalimumab administrations for relentless placoid chorioretinitis (RPC) patients. Case Presentation: We report 2 cases of RPC where successful treatments were achieved with adalimumab. A 34-year-old woman developed conjunctival hyperemia, mild iridocyclitis, and multiple atrophic retinal lesions, along with exudative changes that were widespread from the posterior pole to peripheral retina in both eyes. The diagnosis of RPC was made based on the characteristic recurrences of choroiditis despite systemic corticosteroid and cyclosporine. Adalimumab therapy was introduced to the patient, and thereafter no recurrence was observed while tapering the immunosuppressive agents. The second case was a 22-year-old man with visual deterioration in both eyes who exhibited widespread multiple chorioretinal atrophic lesions. We diagnosed the case as RPC based on characteristic clinical findings and recurring chorioretinitis during tapering of systemic corticosteroids. Adalimumab therapy was administrated, and immunosuppressant dosage was successfully reduced without any recurrences. Conclusions: In the current two RPC cases, adalimumab was quite effective and useful to reduce the dosages of systemic immunosuppressants. Further study is necessary to confirm the effectiveness of adalimumab in RPC patients.

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Screening Children with a Family History of Central Congenital Hypoventilation Syndrome

Case Reports in Pediatrics ◽

10.1155/2020/2713606 ◽

2020 ◽

Vol 2020 ◽

pp. 1-4

Author(s):

Hina Emanuel ◽

Kimberly Rennie ◽

Kelly Macdonald ◽

Aravind Yadav ◽

Ricardo A. Mosquera

Keyword(s):

Family History ◽

Genetic Disorder ◽

Neuropsychological Testing ◽

Clinical Manifestations ◽

Case Series ◽

Blood Gas Analysis ◽

Cor Pulmonale ◽

Gas Analysis ◽

Neuropsychological Evaluations ◽

Hypoventilation Syndrome

Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder of an autonomic nervous disorder that affects breathing. It is characterized by respiratory insufficiency secondary to insensitivity to hypoxemia and hypercarbia, particularly during sleep leading to persistent apnea. We report four individuals across two generations harboring heterozygous 25 polyalanine repeats mutations (PARMs) in PHOX2B with a varying degree of phenotypic clinical manifestations. Two family members who reported to be “asymptomatic” were subsequently diagnosed with CCHS, based on genetic testing, obtained because of their family history. Genetic studies in the family including a mother and three offsprings revealed in-frame five amino acid PARMs of PHOX2B consistent with CCHS in addition to full clinical assessment. All affected individuals had evidence of hypercapnia on blood gas analysis with PCO2 in the range of 32–70 (mean; 61). Nocturnal polysomnogram revealed evidence of hypoventilation in two individuals (1 offspring and mother) with the end-tidal CO2 median of 54. Magnetic resonance imaging of brain revealed no abnormalities in the brain stem. There was no evidence of cor pulmonale on echocardiograms in all individuals. Neuropsychological testing was conducted on all four patients; two patients (mother and 1 offspring) had normal results, while the other two offspring exhibited some impairments on neuropsychological testing. This case series emphasizes the importance of screening first-degree relatives of individuals with confirmed CCHS to minimize complications associated with long-term ventilatory impairment. It also suggests that some patients with CCHS should undergo neuropsychological evaluations to assess for cognitive weaknesses secondary to their CCHS.

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Cannabis Vaping–Induced Acute Pulmonary Toxicity: Case Series and Review of Literature

Journal of Investigative Medicine High Impact Case Reports ◽

10.1177/2324709620947267 ◽

2020 ◽

Vol 8 ◽

pp. 232470962094726

Author(s):

Sreedhar Adapa ◽

Vijay Gayam ◽

Venu Madhav Konala ◽

Srinadh Annangi ◽

Mina P. Raju ◽

...

Keyword(s):

Respiratory Failure ◽

Acute Respiratory Failure ◽

Health Care Providers ◽

Management Strategies ◽

Clinical Manifestations ◽

Case Series ◽

Clinical Findings ◽

Care Providers ◽

Medicinal Use ◽

Common Laboratory

The use of cannabis for recreational as well as medicinal use is on the rise recently with more states legalizing it. We conducted a review analysis of the literature published on acute respiratory failure from vaping cannabis oil. We have also summarized the clinical details (age, length of stay, mode of ventilation, common clinical findings, and steroid use) along with common laboratory abnormalities. This article aims to educate health care providers on the clinical manifestations and management strategies for vaping-induced acute respiratory failure. We also discussed the different available formulations of cannabis oil and key ingredients responsible for the vaping-associated lung injury.

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Ophthalmic Manifestations of Neurologic, Rheumatologic, and Infectious Diseases in the Context of the novel Coronavirus Disease 2019 Pandemic: A Case Series

Journal of Medical Clinical Case Reports ◽

10.47485/2767-5416.1023 ◽

2021 ◽

Keyword(s):

Infectious Diseases ◽

Clinical Manifestations ◽

Case Series ◽

Clinical Findings ◽

The Novel ◽

Altered Level ◽

Multiple Systems ◽

Ocular Manifestations ◽

Ophthalmic Manifestations ◽

Novel Coronavirus

The novel Coronavirus Disease 2019 (COVID-19) is known to present with a broad range of clinical manifestations. While symptoms such as fever, cough, dyspnea, myalgias, diarrhea, anosmia, and ageusia predominate, less common manifestations involving multiple systems have also been described. Some reported ocular manifestations include symptoms associated with keratoconjunctivitis, such as chemosis, ocular pain, photophobia, dry eye and tearing [1]. Neurological symptoms in addition to smell and taste dysfunction have been commonly described as well, and include headache, ataxia, dizziness, altered level of consciousness, and stroke [2]. Whether these neuro-ophthalmologic findings reflect direct involvement of these systems or a more generalized response to SARS-CoV-2 infection remains uncertain. Many other neurologic, rheumatologic, and infectious diseases also present with similar clinical findings as those described in COVID-19, further complicating the diagnostic picture. In this case series, we examine several patients presenting with unusual neuro-ophthalmological manifestations and discuss similarities of these findings with those seen in SARS-CoV-2 infection, and review current literature describing possible mechanisms underlying similar findings in patients with confirmed COVID-19.

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HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS IN ADULTS: LOW INCIDENCE OF PRIMARY NEOPLASM AS A TRIGGER IN A CASE SERIES FROM TURKEY

Mediterranean Journal of Hematology and Infectious Diseases ◽

10.4084/mjhid.2018.047 ◽

2018 ◽

Vol 10 (1) ◽

pp. e2018047

Author(s):

Ferhat Arslan

Keyword(s):

Hemophagocytic Lymphohistiocytosis ◽

Laboratory Data ◽

Case Series ◽

Rheumatologic Diseases ◽

Primary Neoplasm ◽

The Mean ◽

Time To Detection ◽

Low Incidence ◽

Turkish Patients ◽

Erythrocyte Sedimentation Rates

This study aimed to investigate the clinical and laboratory features and outcomes of Turkish patients with Hemophagocytic Lymphohistiocytosis. The medical records of 26 HLH adult patients (≥ 16 years of age) were retrospectively analyzed. Gender, age, the duration of fever, time to diagnosis, etiology and laboratory data were extracted from the records. The mean age was 38 ± 18 years, and 15 (58%) patients were female. A total of nine cases had infectious diseases, four cases had rheumatologic diseases, three cases had hematological malignancies while nine cases could not be obtained a definitive diagnosis. The median time to detection of HLH was 20 days (IQR: 8-30 d). Of the 25 patients, 11 (44%) died. The erythrocyte sedimentation rates of the surviving and non-surviving patients were 39 ± 22 mm/h and 15 ± 13 mm/h, respectively. When a long-lasting fever is complicated by bicytopenia or pancytopenia (especially), clinicians must promptly consider the possibility of HLH syndrome to improve patients’ prognosis

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A novel mutation in a newborn baby leading to glycogen storage disease type Ia

Balkan Journal of Medical Genetics ◽

10.2478/bjmg-2018-0018 ◽

2018 ◽

Vol 21 (2) ◽

pp. 55-57

Author(s):

S Dorum ◽

O Gorukmez

Keyword(s):

Glycogen Storage Disease ◽

Storage Disease ◽

Novel Mutation ◽

Direct Sequencing ◽

Clinical Manifestations ◽

Glycogen Storage Disease Type ◽

Glycogen Storage ◽

Clinical Findings ◽

Disease Type ◽

Type Ia

Abstract Glycogen storage disease type Ia (GSD1A) is caused by mutations in the G6PC gene. The G6PC gene was first cloned in 1993. Since then, many different mutations have been identified leading to this disease. Hepatomegaly is one of the important clinical manifestations of the disease. A 23-day-old girl was admitted to the hospital due to respiratory distress. Her physical examination was normal except for tachypnea. She had hypoglycemia, lactic academia, hyperlipidemia and hyperuricemia. With these clinical findings, GSD1A was considered in the patient and the diagnosis was genetically confirmed. By direct sequencing of the G6PC gene, we identified a novel homozygous variation (c.137T>G/p.Leu46Arg) in the patient and the healthy mother and father were heterozygotes for the variant. Here we present a case with a novel homozygous missense mutation c.137T>G/p.Leu46Arg in the G6PC gene leading to GSD1A clinical findings except early hepatomegaly. These findings expand the spectrum of causative mutations, and clinical findings in GSD1A.

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