scholarly journals Intracranial Calcification Associated with 3-Methylcrotonyl-CoA Carboxylase Deficiency

2021 ◽  
pp. 1-6
Author(s):  
Süleyman Şahin ◽  
Miraç Yıldırım ◽  
Ömer Bektaş ◽  
İlknur Sürücü Kara ◽  
Ahmet Cevdet Ceylan ◽  
...  
Keyword(s):  
Clinical Manifestations ◽  
Cerebellar Atrophy ◽  
Clinical Findings ◽  
Organic Aciduria ◽  
Intracranial Calcification ◽  
Cranial Computed Tomography ◽  
Global Developmental Delay ◽  
Homozygous Mutation ◽  
Screening Programs ◽  
Intracranial Calcifications

3-methylcrotonyl-CoA carboxylase (3-MCC) deficiency is the most frequent organic aciduria detected in newborn screening programs. It demonstrates a variable heterogeneous clinical phenotype, ranging from neonatal onset with severe neurological disorders to asymptomatic adult forms. Herein, we report the first 2 related cases of 3-MCC deficiency presenting with intracranial calcification in the literature. A girl and a boy aged 3 years, 9 months and 4 years were included in the study. The main clinical manifestations were acquired microcephaly, global developmental delay, intractable seizures, mild feeding difficulty, and intermittent dystonic contractions. On physical and neurological examinations, their weights, heights, and head circumferences were below the 3rd percentile, they had acquired microcephaly, truncal hypotonia, upper and lower limb spasticity, hyperreflexia, positive bilateral Babinski signs, and clonus. The detailed biochemical and metabolic tests were unremarkable, except blood 3-hydroxyisovalerylcarnitine (C5OH) was slightly increased in case 1. Cranial computed tomography demonstrated mild cerebral and cerebellar atrophy as well as bilateral periventricular and thalamic calcifications in both cases. We identified a homozygous mutation of c.1015G&#x3e;A (p.V339M) in the <i>MCCC2</i>gene, and the mutation was confirmed by Sanger sequencing. To the best of our knowledge, our cases are the first reported describing intracranial calcification in cases with 3-MCC deficiency. This report expands on the underlying causes of intracranial calcifications and suggests that 3-MCC deficiency may have intracranial calcifications on bilateral thalamus and periventricular white matters. If clinical findings show intracranial calcification, 3-MCC deficiency should also be kept in mind.

scholarly journals Neuronal Ceroid Lipofuscinosis Type 6 (CLN6) clinical findings and molecular diagnosis: Costa Rica’s experience

2022 ◽  
Vol 17 (1) ◽  
Author(s):  
R. Badilla-Porras ◽  
A. Echeverri-McCandless ◽  
J. M. Weimer ◽  
A. Ulate-Campos ◽  
A. Soto-Rodríguez ◽  
...  
Keyword(s):  
Clinical Diagnosis ◽  
Clinical Characteristics ◽  
Clinical Manifestations ◽  
Cerebellar Atrophy ◽  
Batten Disease ◽  
Costa Rican ◽  
Common Element ◽  
Neuronal Ceroid Lipofuscinoses ◽  
Molecular Testing ◽  
Homozygous Mutation

Abstract Background Commonly known as Batten disease, the neuronal ceroid lipofuscinoses (NCLs) are a genetically heterogeneous group of rare pediatric lysosomal storage disorders characterized by the intracellular accumulation of autofluorescent material (known as lipofuscin), progressive neurodegeneration, and neurological symptoms. In 2002, a disease-causing NCL mutation in the CLN6 gene was identified (c.214G > T) in the Costa Rican population, but the frequency of this mutation among local Batten disease patients remains incompletely characterized, as do clinical and demographic attributes for this rare patient population. Objective To describe the main sociodemographic and clinical characteristics of patients with a clinical diagnosis for Batten Disease treated at the National Children's Hospital in Costa Rica and to characterize via molecular testing their causative mutations. Methods DNA extracted from buccal swabs was used for CLN6 gene sequencing. Participants’ sociodemographic and clinical characteristics were also obtained from their medical records. Results Nine patients with a clinical diagnosis of Batten disease were identified. Genetic sequencing determined the presence of the previously described Costa Rican homozygous mutation in 8 of 9 cases. One patient did not have mutations in the CLN6 gene. In all cases where the Costa Rican CLN6 mutation was present, it was accompanied by a substitution in intron 2. Patients were born in 4 of the 7 Costa Rican provinces, with an average onset of symptoms close to 4 years of age. No parental consanguinity was present in pedigrees. Initial clinical manifestations varied between patients but generally included: gait disturbances, language problems, visual impairment, seizures and psychomotor regression. Cortical and cerebellar atrophy was a constant finding when neuroimaging was performed. Seizure medication was a common element of treatment regimens. Conclusions This investigation supports that the previously characterized c.214G > T mutation is the most common causative NCL mutation in the Costa Rican population. This mutation is geographically widespread among Costa Rican NCL patients and yields a clinical presentation similar to that observed for CLN6 NCL patients in other geographies.

scholarly journals Neuronal Ceroid Lipofuscinosis Type 6 (CLN6) Clinical Findings and Molecular Diagnosis: Costa Rica´s Experience

2021 ◽  
Author(s):  
Ramses Badilla-Porras ◽  
Ann Echeverri-McCandless ◽  
Jill Weiner ◽  
Adriana Ulate-Campos ◽  
Andrés Soto-Rodríguez ◽  
...  
Keyword(s):  
Costa Rica ◽  
Clinical Diagnosis ◽  
Clinical Characteristics ◽  
Clinical Manifestations ◽  
Cerebellar Atrophy ◽  
Batten Disease ◽  
Costa Rican ◽  
Common Element ◽  
Neuronal Ceroid Lipofuscinoses ◽  
Homozygous Mutation

Abstract Background: Commonly known as Batten disease, the neuronal ceroid lipofuscinoses (NCLs) are a genetically heterogeneous group of rare pediatric lysosomal storage disorders characterized by the intracellular accumulation of autofluorescent material (known as lipofuscin), progressive neurodegeneration, and neurological symptoms. In 2002, a disease-causing NCL mutation in the CLN6 gene was identified (c.214G>T) in the Costa Rican population, but the frequency of this mutation among local Batten disease patients remains incompletely characterized, as do clinical and demographic attributes for this rare patient population.Objective: To describe the main sociodemographic and clinical characteristics of patients with a clinical diagnosis for Batten Disease treated at the National Children's Hospital in Costa Rica and to genetically characterize their causative mutations.Methods: CLN6 gene sequences were determined from DNA extracted from patient buccal swabs. Participants’ sociodemographic and clinical characteristics were also obtained from their medical records.Results: Nine patients with a clinical diagnosis of Batten disease were identified. Genetic sequencing determined the presence of the previously-described Costa Rican homozygous mutation in 8 of 9 cases. One patient did not have mutations in the CLN6 gene. In all cases where the Costa Rican CLN6 mutation was present, it was accompanied by a substitution in intron 2. Patients were born in 4 of the 7 Costa Rican provinces, with an average onset of symptoms close to 4 years of age. No parental consanguinity was present in pedigrees. Initial clinical manifestations varied between patients but generally included: gait disturbances, language problems, visual impairment, seizures and psychomotor regression. Cortical and cerebellar atrophy was a constant finding when neuroimaging was performed. Seizure medication was a common element of treatment regimens.Conclusions: This investigation supports that the previously characterized c.214G>T mutation is the most common causative NCL mutation in the Costa Rican population. This mutation is geographically widespread among Costa Rican NCL patients and yields a clinical presentation similar to that observed for CLN6 NCL patients in other geographies.

scholarly journals CEREBELLAR ATROPHY WITH LONG-TERM PHENYTOIN (PHT) USE: CASE REPORT

2017 ◽  
Vol 16 (3) ◽  
pp. 123-125
Author(s):  
Jamir P. Rissardo ◽  
◽  
Ana L.F. Caprara ◽  
Juliana O.F. Silveira ◽  
◽  
...  
Keyword(s):  
Clinical Manifestations ◽  
Cerebellar Atrophy ◽  
Clinical History ◽  
Cranial Computed Tomography ◽  
Cerebellar Dysfunction ◽  
Ataxic Gait ◽  
History Of ◽  
Normal Speech ◽  
Cerebellar Symptoms

Cerebellar atrophy can be found with long-term phenytoin (PHT) use or acute phenytoin intoxication. PHT may cause cerebellar symptoms, such as nystagmus, diplopia, dysarthria and ataxia. Clinical manifestations may be persistent. We report a case of a 41-year-old male who presented with cerebellar dysfunction and cerebellar atrophy after longterm phenytoin use. He had ataxic gait, preserved strength, commuting deep reflexes, dysmetria, dysdiadochocinesia, scanning speech and somnolence. Cranial computed tomography revealed enlargement of interfollicular cerebrospinal fluid spaces in cerebellum and also a slight enlargement of the fourth ventricle, suggesting signs of cerebellar volumetric reduction. PHT was withdrawn. Six months later, he presented improvement in his condition; he had atypical gait, mild dysmetria, diadochokinesia and normal speech. In conclusion, clinicians should be vigilant with patients on phenytoin. If the patient has cerebellar signs with a correspondent clinical history of phenytoin intoxication CT scan should be helpful as an initial cerebellar assessment.

scholarly journals A familial case of CAMK2B mutation with variable expressivity

2021 ◽  
Vol 9 ◽  
pp. 2050313X2199098
Author(s):  
Paige Heiman ◽  
Sarah Drewes ◽  
Lina Ghaloul-Gonzalez
Keyword(s):  
Intellectual Disability ◽  
De Novo ◽  
Neurodevelopmental Disorder ◽  
Clinical Manifestations ◽  
Cerebellar Atrophy ◽  
Global Developmental Delay ◽  
De Novo Mutations ◽  
Phenotypic Spectrum ◽  
Behavioral Abnormalities ◽  
Intrafamilial Variability

Variants in CAMK2-associated genes have recently been implicated in neurodevelopmental disorders and intellectual disability. The clinical manifestations reported in patients with mutations in these genes include intellectual disability (ranging from mild to severe), global developmental delay, seizures, delayed speech, behavioral abnormalities, hypotonia, episodic ataxia, progressive cerebellar atrophy, visual impairments, and gastrointestinal issues. Phenotypic heterogeneity has been postulated. We present a child with neurodevelopmental disorder caused by a pathogenic CAMK2B variant inherited from a healthy mother. A more mildly affected sib was determined to have the same variant. Monoallelic mutations in CAMK2B in patients have previously only been reported as de novo mutations. This report adds to the clinical phenotypic spectrum of the disease and demonstrates intrafamilial variability of expression of a CAMK2B mutation.

Nutritional B12 Deficiency in Infants of Vitamin B12-Deficient Mothers

2011 ◽  
Vol 81 (5) ◽  
pp. 328-334 ◽  
Author(s):  
Oya Halicioglu ◽  
Sezin Asik Akman ◽  
Sumer Sutcuoglu ◽  
Berna Atabay ◽  
Meral Turker ◽  
...  
Keyword(s):  
Megaloblastic Anemia ◽  
Maternal Diet ◽  
Clinical Manifestations ◽  
Serum Vitamin ◽  
Failure To Thrive ◽  
Clinical Findings ◽  
Vitamin B ◽  
Animal Products ◽  
Hematological Evaluation ◽  
Nutritional Vitamin

Aim: Nutritional vitamin B12 deficiency in infants may occur because the maternal diet contains inadequate animal products. Clinical presentations of the infants who had nutritional vitamin B12 deficiency were analyzed in this study. Subjects and Methods: Patients with nutritional vitamin B12 deficiency were enrolled in the study between 2003 and 2010. The diagnosis was based on a nutritional history of mothers and infants, clinical findings, hematological evaluation, and low level of serum vitamin B12. Results: Thirty children aged 1 - 21 months constituted the study group. Poverty was the main cause of inadequate consumption of animal products of the mothers. All infants had predominantly breastfed. The most common symptoms were developmental delay, paleness, apathy, lethargy, anorexia, and failure to thrive. Hematological findings were megaloblastic anemia (83.3 %), thrombocytopenia (30 %), and severe anemia (13.3 %). All of the mothers had low serum B12 levels; eight of them had megaloblastic anemia. Conclusion: The unusual clinical manifestations of vitamin B12 deficiency may also be seen apart from neurological and hematological findings. Nutritional vitamin B12 deficiency due to maternal deficiency might be a serious health problem in infants. Therefore, screening and supplementation of pregnant and lactating women to prevent infantile vitamin B12 deficiency should be considered.

Scabies: A Neglected Global Disease

2020 ◽  
Vol 16 (1) ◽  
pp. 33-42 ◽  
Author(s):  
Alexander K.C. Leung ◽  
Joseph M. Lam ◽  
Kin F. Leong
Keyword(s):  
English Language ◽  
Clinical Manifestations ◽  
Skin Lesions ◽  
Sarcoptes Scabiei ◽  
Clinical Findings ◽  
Effective Control ◽  
Search Term ◽  
Skin Contact ◽  
Intense Pruritus ◽  
Meta Analyses

Background: Scabies is a skin disease caused by an obligate human parasite mite Sarcoptes scabiei var. hominis. Children under the age of two and elderly individuals are at the greatest risk. Knowledge of this condition is important for an early diagnosis to be made and treatment to be initiated. Objective: The review aimed to familiarize physicians with the clinical manifestations, diagnosis, evaluation, and management of scabies. Methods: A search was conducted using Pubmed with the built-in "Clinical Queries" tool. The search term "Scabies" was used. The categories of "epidemiology", "diagnosis", "therapy", "prevention" and "prognosis" had a limited scope for primary clinical studies. Meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews were included. Only papers published in the English language were included. A descriptive, narrative synthesis was provided of the retrieved articles. Results: Worldwide, scabies affects 200 to 300 million individuals annually. The average prevalence is estimated to be 5 to 10% in children of developing countries. Transmission usually occurs after close prolonged skin-to-skin contact. Classic scabies is characterized by an erythematous papular eruption, serpiginous burrows, and intense pruritus. Sites of predilection include the webs of the fingers, volar wrists, lateral aspects of fingers, extensor surfaces of elbows and knees, waist, navel, abdomen, buttocks, groins, and, genitals. A clinical diagnosis of classic scabies can be made on the basis of the history and clinical findings. Other clinical variants include crusted scabies, nodular scabies, and bullous scabies. Finding the mite, ova, or fecal pellets on microscopic examination of scrapings taken from skin lesions confirms the diagnosis of scabies infestation. For eradication of scabies mites, the drugs of choice are topical permethrin and oral ivermectin. Conclusion: Scabies is a highly contagious parasitic cutaneous disease that is stigmatising and debilitating. Increased awareness, accurate diagnosis, and prompt treatment are essential for the effective control of scabies and for the prevention of the spread of the disease.

scholarly journals A Clinical-Based Diagnostic Approach to Cerebellar Atrophy in Children

2021 ◽  
Vol 11 (5) ◽  
pp. 2333
Author(s):  
Claudia Ciaccio ◽  
Chiara Pantaleoni ◽  
Franco Taroni ◽  
Daniela Di Bella ◽  
Stefania Magri ◽  
...  
Keyword(s):  
Muscle Biopsy ◽  
Single Gene ◽  
Brain Mri ◽  
Genetic Defect ◽  
Cerebellar Atrophy ◽  
Chain Complex ◽  
Clinical Findings ◽  
Diagnostic Workup ◽  
Diagnostic Approach ◽  
Disease Definition

Background: Cerebellar atrophy is a neuroradiological definition that categorizes conditions heterogeneous for clinical findings, disease course, and genetic defect. Most of the papers proposing a diagnostic workup for pediatric ataxias are based on neuroradiology or on the literature and experimental knowledge, with a poor participation of clinics in the process of disease definition. Our study aims to offer a different perspective on the way we approach cerebellar atrophy in developmental age, building a clinical-based diagnostic workup to guide molecular diagnosis. Methods: we recruited 52 patients with pediatric-onset cerebellar atrophy and definite disease categorization. Children underwent brain MRI, neurophysiological exams, metabolic investigations, and muscle biopsy with respiratory chain complex study. Single-gene sequencing, next-generation sequencing NGS panels, whole-exome sequencing (WES), and disease-specific techniques have been used to reach genetic confirmation. Results: Brain MRI is the main method of diagnosis, followed by tests on muscle biopsy and peripheral nervous system study. Other exams (e.g., metabolic investigations or evoked potentials) may be useful to narrow the list of diagnostic possibilities. Conclusions: We propose a diagnostic approach to cerebellar atrophy in children based on clinical findings, and support the evidence that a precise phenotypic definition may lead to the formulation of a definite diagnosis or otherwise guide the back phenotyping process derived from large molecular data.

scholarly journals Neuralgic amyotrophy: an underrecognized entity

2021 ◽  
Vol 49 (4) ◽  
pp. 030006052110065
Author(s):  
Tae Uk Kim ◽  
Min Cheol Chang
Keyword(s):  
Clinical Practice ◽  
Magnetic Resonance ◽  
Clinical Manifestations ◽  
Clinical History ◽  
Cervical Radiculopathy ◽  
Sudden Onset ◽  
Clinical Findings ◽  
Magnetic Resonance Neurography ◽  
Essential Information ◽  
Neuralgic Amyotrophy

Neuralgic amyotrophy (NA) is markedly underdiagnosed in clinical practice, and its actual incidence rate is about 1 per 1000 per year. In the current article, we provide an overview of essential information about NA, including the etiology, clinical manifestations, diagnostic investigations, differential diagnosis, treatment, and prognosis. The causes of NA are multifactorial and include immunological, mechanical, or genetic factors. Typical clinical findings are a sudden onset of pain in the shoulder region, followed by patchy flaccid paralysis of muscles in the shoulder and/or arm. A diagnosis of NA is based on a patient’s clinical history and physical examination. Gadolinium-enhanced magnetic resonance imaging and high-resolution magnetic resonance neurography are useful for confirming the diagnosis and choosing the appropriate treatment. However, before a diagnosis of NA is confirmed, other disorders with similar symptoms, such as cervical radiculopathy or rotator cuff tear, need to be ruled out. The prognosis of NA depends on the degree of axonal damage. In conclusion, many patients with motor weakness and pain are encountered in clinical practice, and some of these patients will exhibit NA. It is important that clinicians understand the key features of this disorder to avoid misdiagnosis.

scholarly journals Frontal Hypoperfusion and the Effectiveness of Perampanel in Long-Lived Patient with Lafora Disease

2021 ◽  
pp. 211-217
Author(s):  
Koji Obara ◽  
Erika Abe ◽  
Itaru Toyoshima
Keyword(s):  
Single Photon ◽  
Early Stage ◽  
Photon Emission ◽  
Cerebellar Atrophy ◽  
Brain Magnetic Resonance Imaging ◽  
Emission Computed Tomography ◽  
Homozygous Mutation ◽  
Lafora Disease ◽  
Mental Deterioration ◽  
Exon 1

We report a long-lived patient with Lafora disease (LD). A 34-year-old woman experienced onset of seizures at the age of 11 years. She was bedridden in her early twenties due to frequent generalized tonic-clonic seizures, myoclonus, and progressive mental deterioration. Her seizures occurred all the time despite administration of multiple anticonvulsants at high doses. At the age of 31, she started perampanel, which resulted in reduction of anticonvulsants after her visible myoclonus and convulsions disappeared. Brain magnetic resonance imaging showed marked cerebral and cerebellar atrophy, and single-photon emission computed tomography using N-isopropyl-p-[123I] iodoamphetamine (IMP-SPECT) revealed significant hypoperfusion of the frontal lobe and cerebellum. We identified a W219R homozygous mutation in exon 1 of the NHLRC1 gene. Because perampanel may not only control seizures but also prevent mental deterioration in LD, we propose that perampanel should be administered from the early stage of LD.

scholarly journals Chikungunya Manifestations and Viremia in Patients Who Presented to the Fever Clinic at Bangkok Hospital for Tropical Diseases during the 2019 Outbreak in Thailand

2021 ◽  
Vol 6 (1) ◽  
pp. 12
Author(s):  
Hisham A Imad ◽  
Juthamas Phadungsombat ◽  
Emi E Nakayama ◽  
Sajikapon Kludkleeb ◽  
Wasin Matsee ◽  
...  
Keyword(s):  
Chikungunya Virus ◽  
Clinical Manifestations ◽  
Clinical Findings ◽  
Acute Stage ◽  
Tropical Diseases ◽  
Healthy Individuals ◽  
Rt Pcr ◽  
Viral Loads ◽  
The Family ◽  
Systemic Symptoms

Chikungunya virus is an Alphavirus belonging to the family Togaviridae that is transmitted to humans by an infected Aedes mosquito. Patients develop fever, inflammatory arthritis, and rash during the acute stage of infection. Although the illness is self-limiting, atypical and severe cases are not uncommon, and 60% may develop chronic symptoms that persist for months or even for longer durations. Having a distinct periodical epidemiologic outbreak pattern, chikungunya virus reappeared in Thailand in December 2018. Here, we describe a cohort of acute chikungunya patients who had presented to the Bangkok Hospital for Tropical Diseases during October 2019. Infection was detected by a novel antigen kit and subsequently confirmed by real-time RT-PCR using serum collected at presentation to the Fever Clinic. Other possible acute febrile illnesses such as influenza, dengue, and malaria were excluded. We explored the sequence of clinical manifestations at presentation during the acute phase and associated the viral load with the clinical findings. Most of the patients were healthy individuals in their forties. Fever and arthralgia were the predominant clinical manifestations found in this patient cohort, with a small proportion of patients with systemic symptoms. Higher viral loads were associated with arthralgia, and arthralgia with the involvement of the large joints was more common in female patients.

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