Hypoparathyroidism,neutropenia and nephrotic syndrome in a patient with mitochondrial trifunctional protein deficiency: A case report and review of the literature |
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| Affiliation: | 1. Department of Neurology, Children''s Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, 400014, China;2. China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing, 400014, China;3. Chongqing Key Laboratory of Pediatrics, Chongqing, 400014, China;1. Laboratory of Molecular and Cellular Screening Processes (LPCMC), Center of Biotechnology of Sfax, University of Sfax, Tunisia;2. Medical Genetics Department, University Hedi Chaker Hospital of Sfax, Tunisia;3. Child Neurology Department, University Hedi Chaker Hospital of Sfax, Tunisia;4. Research Laboratory “Neuropédiatrie" LR19ES15, Sfax University, Tunisia;5. Radiology Department, Hedi Chaker University Hospital, University of Sfax, Sfax, Tunisia;6. Department of Ophthalmology, Habib Bourguiba Hospital, Sfax, Tunisia;7. Department of Otorhinolaryngology, University Habib Bourguiba Hospital of Sfax, Tunisia;8. Laboratory of Human Molecular Genetics, LR33ES99, Faculty of Medicine of Sfax, University of Sfax, Sfax, Tunisia;9. Department of Applied Biology, College of Sciences, University of Sharjah, Sharjah, United Arab Emirates;10. Human Genetics and Stem Cell Laboratory, Research Institute of Sciences and Engineering, University of Sharjah, Sharjah, United Arab Emirates;11. Medical Research, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates;1. i3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal;2. IBMC – Institute for Molecular and Cell Biology, Universidade do Porto, Portugal;3. Centre for Predictive and Preventive Genetics (CGPP), Universidade do Porto, Portugal;4. Faculty of Psychology and Education Sciences, University of Porto, Porto, Portugal;5. CHUC - Medical Genetics Unit, Hospital Pediátrico, Centro Hospitalar e Universitário de Coimbra, Portugal;6. CHULN-HSM – Serviço de Genética Médica, Centro Hospitalar Universitário de Lisboa Norte – Hospital de Santa Maria, Portugal;7. EPER – Hospital de Santo Espírito da Ilha Terceira, Portugal;8. HB - Unidade de Genética Médica, Hospital de Braga, Portugal;9. ICBAS – Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Portugal;10. ICVS/3B''s, PT Government Associate Laboratory, Braga/Guimarães, Portugal;11. Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal;12. Centro de Psicologia, Universidade do Porto, Porto, Portugal;1. Centre for Human Genetics, Institut de Pathologie et de Génétique, Charleroi, Gosselies, Belgium;2. Laboratory of Microbiology, Bioorganic and Macromolecular Chemistry, Université Libre de Bruxelles, Brussels, Belgium;3. Telomeres Research Group, Genetic & Epigenetic Alterations of Genomes, de Duve Institute, Université catholique de Louvain, Brussels, Belgium;4. IPG BioBank and Laboratory of Translational Oncology, Institut de Pathologie et de Génétique/Grand Hôpital de Charleroi, Gosselies, Belgium;5. Department of Anatomopathology, Cliniques de Mont-Godinne, CHU-UCL-Namur, Godinne, Belgium;6. UCLouvain, Cliniques Universitaires St Luc, Service de Gastroentérologie et Hépatologie Pédiatrique, 10 Av Hippocrate, Bruxelles, Belgium;7. Department of Endocrinology, Vivalia, Cliniques Sud Luxembourg, Arlon, Belgium;8. Department of Oto-Rhino-Laryngology, Vivalia, Cliniques Sud Luxembourg, Arlon, Belgium;9. Department of Orthopedic Surgery, Vivalia, Cliniques Sud Luxembourg, Arlon, Belgium;10. Department of Hepato-Gastro-Enterology, Cliniques de Mont-Godinne, CHU-UCL-Namur, Godinne, Belgium;11. Faculty of Medicine, Unamur, Namur, Belgium;1. Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Ida Scudder Road, Vellore, Tamil Nadu, India;2. Department of Paediatric Endocrinology, Christian Medical College, Ida Scudder Road, Vellore, Tamil Nadu, India;3. Department of Biochemistry, Christian Medical College, Ida Scudder Road, Vellore, Tamil Nadu, India;4. Department of Clinical Genetics, Aster MIMS, Calicut, Kerala, India;1. Neurogenetics Unit, Hospital JM Ramos Mejía, Buenos Aires, Argentina;2. Precision Medicine and Clinical Genomics Group, Translational Medicine Research Institute-CONICET, Faculty of Biomedical Sciences, Universidad Austral, Buenos Aires, Argentina;3. Paediatric Neurology Unit, Hospital Universitario Austral, Buenos Aires, Argentina;4. CETES, Instituto de Neurología Infanto-Juvenil, Córdoba, Argentina;5. Paediatric Neurology Unit, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina;6. Genetic Unit, Hospital Aleman, Buenos Aires, Argentina |
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| Abstract: | ![]()
IntroductionMitochondrial trifunctional protein (TFP) deficiency is an autosomal recessive disorder that causes a clinical spectrum of diseases ranging from severe infantile cardiomyopathy to mild chronic progressive neuromyopathy, however, parathyroid glands, hematologic system and kidney damage are not the common presentations of this disease.MethodsWe describe the clinical, biochemical and molecular features of the TFP deficiency patient at our institution. We also provide an extensive literature review of previous published cases with emphasis on the clinical/biochemical phenotype-genotype correlation of this disorder.ResultsOur case is a complete TFP deficiency patient dominated presented with hypoparathyroidism, neutropenia and nephrotic syndrome, which caused by compound heterozygoues variants in HADHB gene. Based on the retrospective study of 157 cases, TFP patients presented with diverse clinical, biochemical and molecular features. The onset age is typically before early childhood. Neuromuscular system is more vulnerable involved. Severe form is generally characterized by multiorgan involvement. A notable feature of severe and intermediate form is respiratory failure. Neuropathy and rhabdomyolysis are the typical manifestations of mild form. Increased long-chain 3-OH-acylcarnitines (C16–OH, C18:1-OH) are the most common biochemical finding. The mortality of the present study is as high as 57.9%, which is linked with the onset age, phenotype, mutation type and muscular histology. Mutations in HADHB are more frequent in Asian descent with complete TFP deficiency and usually presented with atypical presentations. The type of mutation, rather than residual enzyme activity seem to be more related to the phenotype and prognosis. The most common HADHA variant is 1528G > C, no common HADHB variant were detected.ConclusionsTFP deficiency is heterogeneous at both the molecular and phenotypic levels, generally a high mortality. Although there is no strict clinical/biochemical phenotype-genotype correlation, difference in ethnic and subunit mutations still have certain characteristics. |
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| Keywords: | Mitochondrial trifunctional protein deficiency Hypoparathyroidism Case report Literature review |
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