scholarly journals Schizophrenic Psychosis Symptoms in a Background of Mild-To-Moderate Carnitine Palmitoyltransferase II Deficiency: A Case Report

Reports ◽  
2020 ◽  
Vol 3 (4) ◽  
pp. 31
Author(s):  
Rochelle N. Wickramasekara ◽  
Pashayar P. Lookian ◽  
Jeannie Ngo ◽  
Annemarie Shibata ◽  
Holly A. F. Stessman
Keyword(s):  
Carnitine Palmitoyltransferase ◽  
Adolescent Male ◽  
Mitochondrial Inner Membrane ◽  
Complex Phenotypes ◽  
Whole Exome ◽  
Biological Parents ◽  
History Of ◽  
Genetic And Environmental Factors ◽  
Carnitine Palmitoyltransferase Ii ◽  
Cpt Ii Deficiency

Schizophrenia is a multifaceted mental illness characterized by cognitive and neurobehavioral abnormalities. Carnitine palmitoyltransferase II (CPT II) deficiency is a metabolic disorder resulting in impaired transport of long-chain fatty acids from the cytosol to the mitochondrial inner membrane, where fatty acid β-oxidation takes place. Here, we present an interesting clinical case of an adolescent male that presented with psychosis and a history of mild-to-moderate CPT II deficiency. To identify germline genetic variation that may contribute to the phenotypes observed, we performed whole-exome sequencing on DNA from the proband, unaffected fraternal twin, and biological parents. The proband was identified to be homozygous for the p.Val368Ile and heterozygous for the p.Met647Val variant in CPT2. Each of these variants are benign on their own; however, their combined effect is unclear. Further, variation was identified in the dopamine β-hydroxylase (DBH) gene (c.339+2T>C), which may contribute to decreased activity of DBH; however, based on the patient’s presentation, severe DBH deficiency is unlikely. In conclusion, the variants identified in this study do not clearly explain the observed patient phenotypes, indicating that the complex phenotypes are likely caused by an interplay of genetic and environmental factors that warrant further investigation.

An ignored cause of red urine in children: rhabdomyolysis due to carnitine palmitoyltransferase II (CPT-II) deficiency

2017 ◽  
Vol 30 (2) ◽  
Author(s):  
Engin Melek ◽  
Fatma Derya Bulut ◽  
Bahriye Atmış ◽  
Berna Şeker Yılmaz ◽  
Aysun Karabay Bayazıt ◽  
...  
Keyword(s):  
Clinical Phenotype ◽  
Carnitine Palmitoyltransferase ◽  
Long Chain Fatty Acids ◽  
Infantile Form ◽  
Dark Urine ◽  
Recurrent Rhabdomyolysis ◽  
History Of ◽  
Carnitine Palmitoyltransferase Ii ◽  
Cpt Ii Deficiency ◽  
Long Chain

AbstractCarnitine palmitoyltransferase II (CPT-II) deficiency is an autosomal recessively inherited disorder involving the β-oxidation of long-chain fatty acids, which leads to rhabdomyolysis and subsequent acute renal failure. The clinical phenotype varies from a severe infantile form to a milder muscle form. Here, we report a 9-year-old boy referred to our hospital for the investigation of hematuria with a 2-day history of dark urine and malaise. As no erythrocytes in the microscopic examination of the urine and hemoglobinuria were present, myoglobinuria due to rhabdomyolysis was the most probable cause of dark urine. After excluding the other causes of rhabdomyolysis, with the help of metabolic investigations, the patient was suspected to have CPT-II deficiency, the most common cause of metabolic rhabdomyolysis. Our aim in presenting this case is to emphasize considering rhabdomyolysis in the differential diagnosis of dark urine in order to prevent recurrent rhabdomyolysis and renal injury.

scholarly journals Familial Intracranial Aneurysm in Newfoundland: Clinical and Genetic Analysis

2019 ◽  
Vol 46 (5) ◽  
pp. 518-526
Author(s):  
Amy E. Powell ◽  
Bridget A. Fernandez ◽  
Falah Maroun ◽  
Barbara Noble ◽  
Michael O. Woods
Keyword(s):  
Intracranial Aneurysm ◽  
Sanger Sequencing ◽  
Variant Prioritization ◽  
Future Studies ◽  
Whole Exome ◽  
High Prevalence ◽  
History Of ◽  
Multiplex Families ◽  
Genetic And Environmental Factors ◽  
Population Controls

ABSTRACT:Objective:Intracranial aneurysm (IA) is an expansion of the weakened arterial wall that is often asymptomatic until rupture, resulting in subarachnoid hemorrhage. Here we describe the high prevalence of familial IA in a cohort of Newfoundland ancestry. We began to investigate the genetic etiology of IA in affected family members, as the inheritance of this disease is poorly understood.Methods:Whole exome sequencing was completed for a cohort of 12 affected individuals from two multiplex families with a strong family history of IA. A filtering strategy was implemented to identify rare, shared variants. Filtered variants were prioritized based on validation by Sanger sequencing and segregation within the families.Results:In family R1352, six variants passed filtering; while in family R1256, 68 variants remained, so further filtering was pursued. Following validation by Sanger sequencing, top candidates were investigated in a set of population controls, namely,C4orf6c.A1G (p.M1V) andSPDYE4c.C103T (p.P35S). Neither was detected in 100 Newfoundland control samples.Conclusion:Rare and potentially deleterious variants were identified in both families, though incomplete segregation was identified for all filtered variants. Alternate methods of variant prioritization and broader considerations regarding the interplay of genetic and environmental factors are necessary in future studies of this disease.

Cryptococcal pneumonia in an adolescent with a gain-of-function variant in signal transduction and activator of transcription 1 (STAT1)

2020 ◽  
Vol 13 (4) ◽  
pp. e234120
Author(s):  
Lisa Marinelli ◽  
Elizabeth Ristagno ◽  
Philip Fischer ◽  
Roshini Abraham ◽  
Avni Joshi
Keyword(s):  
Signal Transduction ◽  
Exome Sequencing ◽  
Opportunistic Infections ◽  
Clinical Phenotype ◽  
Adolescent Male ◽  
Gain Of Function ◽  
Autoimmune Hypothyroidism ◽  
Whole Exome ◽  
History Of ◽  
Antibiotic Courses

An adolescent male with a history of autoimmune enteropathy, autoimmune hypothyroidism, aphthous stomatitis and recurrent oral Candida infections only in the setting of curative antibiotic courses presented with cryptococcal pneumonia and perihilar adenitis, which was successfully treated with antifungal therapy. The patient had a complex history with several immunological anomalies. Whole exome sequencing revealed a known STAT1 pathogenic variant, associated with gain of function (GOF). This case expands our understanding of the broad clinical phenotype manifested by STAT1 GOF and emphasises the importance of consideration of this diagnosis in patients presenting with opportunistic infections and autoimmunity.

Recurrent Myalgia since Early Infancy—Misleading Clinical Course in a Child with Carnitine Palmitoyltransferase-II Deficiency

2019 ◽  
Vol 51 (01) ◽  
pp. 053-056
Author(s):  
Maria Arélin ◽  
Stephan Zierz ◽  
Uta Ceglarek ◽  
Mitja Heinemann ◽  
Skadi Beblo ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Carnitine Palmitoyltransferase ◽  
Early Infancy ◽  
Hereditary Diseases ◽  
Missense Mutations ◽  
Metabolic Myopathies ◽  
Muscle Energy ◽  
Carnitine Palmitoyltransferase Ii ◽  
Cpt Ii Deficiency ◽  
Generation Sequencing

AbstractMetabolic myopathies are heterogeneous hereditary diseases affecting skeletal muscle energy supply. Symptoms usually comprise pain, cramps, hypotonia, weakness, and myoglobinuria.We present a boy with recurrent myalgia and weakness after some minutes of exercise or during febrile infections since early infancy. First laboratory workup at the age of 9 years showed no abnormalities, apart from a slightly elevated creatine kinase. After exclusion of common structural and metabolic myopathies, next generation sequencing panel (4 years after the initial diagnostic metabolic workup) revealed two potentially pathogenic missense mutations in the CPT2 gene (c.149C > A (p.P50H) and c.1459G > A (p.E487K)).Our case underscores the clinical variability of muscle carnitine palmitoyltransferase II (CPT II) deficiency and illustrates a pitfall of diagnostic algorithms for metabolic myopathies. Myalgia following exercise of a few minutes duration would have argued for a carbohydrate and against a fatty acid metabolic defect. However, CPT II deficiency is the most common disorder of muscle fatty acid metabolism and should be considered even in atypical scenarios. Analyses of plasma acyl carnitine profile during acute metabolic crises may help to unmask biochemical markers which are often overlooked in dried-blood analyses.

scholarly journals Normal FGF-21-Serum Levels in Patients with Carnitine Palmitoyltransferase II (CPT II) Deficiency

2019 ◽  
Vol 20 (6) ◽  
pp. 1400 ◽  
Author(s):  
Leila Motlagh Scholle ◽  
Diana Lehmann ◽  
Pushpa Joshi ◽  
Stephan Zierz
Keyword(s):  
Citrate Synthase ◽  
Serum Levels ◽  
Carnitine Palmitoyltransferase ◽  
Fibroblast Growth Factor 21 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Mitochondrial Fatty Acid ◽  
Significant Difference ◽  
Carnitine Palmitoyltransferase Ii ◽  
Cpt Ii Deficiency

Fibroblast growth factor 21 (FGF-21) is known to be a biomarker for mitochondrial disorders. An upregulation of FGF-21 in serum and muscle of carnitine palmitoyltransferase I (CPT I) and carnitine palmitoyltransferase II (CPT II) knock-out mice has been reported. In human CPT II deficiency, enzyme activity and protein content are normal, but the enzyme is abnormally regulated by malonyl-CoA and is abnormally thermolabile. Citrate synthase (CS) activity is increased in patients with CPT II deficiency. This may indicate a compensatory response to an impaired function of CPT II. In this study, FGF-21 serum levels in patients with CPT II deficiency during attack free intervals and in healthy controls were measured by enzyme linked immunosorbent assay (ELISA). The data showed no significant difference between FGF-21 concentration in the serum of patients with CPT II deficiency and that in the healthy controls. The results of the present work support the hypothesis that in muscle CPT II deficiency, in contrast to the mouse knockout model, mitochondrial fatty acid utilization is not persistently reduced. Thus, FGF-21 does not seem to be a useful biomarker in the diagnosis of CPT II deficiency.

Identification of Four Novel Mutations in Patients with Carnitine Palmitoyltransferase II (CPT II) Deficiency

1998 ◽  
Vol 64 (4) ◽  
pp. 229-236 ◽  
Author(s):  
Bing-Zhi Yang ◽  
Jia-Huan Ding ◽  
Tracy Dewese ◽  
Diane Roe ◽  
Guocheng He ◽  
...  
Keyword(s):  
Carnitine Palmitoyltransferase ◽  
Novel Mutations ◽  
Carnitine Palmitoyltransferase Ii ◽  
Cpt Ii Deficiency

scholarly journals Carnitine Palmitoyltransferase II deficiency, a Rare Cause of Rhabdomyolysis: A Case Report

2019 ◽  
Author(s):  
Parisa Farshchi ◽  
Sahar Karimpour Reyhan ◽  
Mahsa Abbaszadeh ◽  
Shadi Shiva
Keyword(s):  
Acute Kidney Injury ◽  
Muscle Weakness ◽  
Muscle Biopsy ◽  
Kidney Injury ◽  
Carnitine Palmitoyltransferase ◽  
Metabolic Myopathy ◽  
Dark Urine ◽  
Recurrent Rhabdomyolysis ◽  
Carnitine Palmitoyltransferase Ii ◽  
Cpt Ii Deficiency

Introduction: Muscle weakness and rhabdomyolysis have a wide range of differential diagnosis. In many situations, they are induced by seizure, trauma, drugs, and toxins. They could also be due to inflammatory or metabolic myopathies. Identifying the exact cause is crucial and sometimes challenging. Case Presentation: A 23-year-old man was admitted to our hospital with muscle weakness, fatigue, dyspnea, and dark urine, all preceded by flu-like symptoms, myalgia, and fever. Due to reduced muscle strength, dark urine, elevated serum creatine kinase, and serum creatinine, he was diagnosed with rhabdomyolysis and acute kidney injury. Muscle biopsy was performed three years before for the patient, due to a history of similar episodes and exercise intolerance. Because of recurrent episodes of muscle weakness and rhabdomyolysis along with the negative muscle biopsy for inflammatory myopathies, we suspected metabolic myopathy as a cause. Therefore, metabolic screening was performed for the patient, and he was diagnosed with metabolic myopathy known as Carnitine Palmitoyltransferase II (CPT II) deficiency. Conclusion: In patients with recurrent rhabdomyolysis, we should consider inherited myopathies, especially carnitine palmitoyltransferase II deficiency and glycogen storage disease type V (McArdle disease) as likely causes. CPT II deficiency is regarded as a preventable cause of recurrent rhabdomyolysis. Therefore, by early diagnosis of this disorder we could prevent recurrent episodes of rhabdomyolysis and ultimately avoid life-threatening complications like acute kidney injury

Cause of recurrent rhabdomyolysis, carnitine palmitoyltransferase II deficiency and novel pathogenic mutation

2021 ◽  
Vol 74 (3-4) ◽  
pp. 135-138
Author(s):  
Nafiye Emel Çakar ◽  
Zeynep Gör ◽  
Gözde Yeşil
Keyword(s):  
Pathogenic Mutation ◽  
Severe Form ◽  
Carnitine Palmitoyltransferase ◽  
Inherited Metabolic Disorder ◽  
Common Causes ◽  
Recurrent Rhabdomyolysis ◽  
Acylcarnitine Analysis ◽  
Carnitine Palmitoyltransferase Ii ◽  
Cpt Ii Deficiency ◽  
Strong Suspicion

Carnitine palmitoyltransferase II (CPT II) deficiency is an autosomal inherited metabolic disorder in which the β-oxidation of the long chain fatty acids is defective. The clinical presentation may be in various forms; it presents itself in the severe form during neonatal and infantile periods and as the less severe myopathic form in the school age and adolescence. While the severity of the rhabdomyolysis attacks varies, occasionally the clinical course may be complicated with acute renal failure. Acylcarnitine analysis may help in the diagnosis of CPT II, but its normality does not indicate the absence of the disease. If there is strong suspicion, genetic analysis should be performed on the cases. In this article, we present a 15-year-old male patient who had two rhabdomyolysis attacks triggered by infection and starvation. Acylcarnitine analysis of the case was normal, CPT II deficiency was considered when the history was evaluated, and CPT II gene c.137A>G (p.Gln46Arg) homozygous novel pathogenic mutation was detected. CPT II deficiency is one of the most common causes of metabolic rhabdomyolysis in patients with recurrent episodes of rhabdomyolysis.

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