Browse
Submit Data
Databases
API
Help

Dataset Information

10 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Long-term outcome of a patient with Transcobalamin deficiency caused by the homozygous c.1115_1116delCA mutation in TCN2 gene: a case report.

ABSTRACT:

Background

Transcobalamin deficiency is a rare autosomal recessive inborn error of cobalamin transport (prevalence: Case presentationWe describe the case of a 31?years old woman who at the age of 30?days presented with the classical clinical and laboratory signs of an inborn error of vitamin B₁₂ metabolism. Family history revealed a sister who died at the age of 3?months with a similar clinical syndrome and with pancytopenia. She was started on empirical intramuscular (IM) cobalamin supplements (injections of hydroxocobalamin 1?mg/day for 1?week and then 1?mg twice a week) and several transfusions of washed and concentrated red blood cells. With these treatments a clear improvement in symptoms was observed, with the disappearance of vomiting, diarrhea and normalization of the full blood count. At 8?years of age injections were stopped for about two and a half months causing the appearance of pancytopenia. IM hydroxocobalamin was then restarted sine die. The definitive diagnosis could only be established at 29?years of age when a genetic evaluation revealed the homozygous c.1115_1116delCA mutation of TCN2 gene (p.Q373GfsX38). Currently she is healthy and she is taking 1?mg of IM hydroxocobalamin once a week.

Conclusions

Our case report highlights that early detection of TC deficiency and early initiation of aggressive IM treatment is likely associated with disease control and an overall favorable outcome.

SUBMITTER: Martino F

PROVIDER: S-EPMC7941906 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Case report: Novel compound-heterozygous mutations in the <i>TCN2</i> gene identified in a chinese girl with transcobalamin deficiency.

Project description:Transcobalamin (TC) deficiency is a rare autosomal recessive disease characterized by megaloblastic anemia. It is caused by cellular vitamin B12 depletion, which subsequently results in elevated levels of homocysteine and methylmalonic acid. This disease is usually diagnosed by genetic analysis of the TCN2 gene. Here, we described a 2.2-month-old Chinese girl with TC deficiency presenting with diarrhea, fever and poor feeding. Whole-exome sequencing detected a pair of compound-heterozygous mutations in TCN2 gene, c.754-12C>G and c.1031_1032delGA (p.R344Tfs*20). To our knowledge, it is the first time that they were identified and reported in TC deficiency. This study contributes to a better understanding of the TC deficiency, expanding the spectrum of TCN2 mutations in this disorder and also supporting the early diagnosis and proper treatment of similar cases in the future.

| S-EPMC9411981 | biostudies-literature

Identification of transcobalamin deficiency with two novel mutations in the TCN2 gene in a Chinese girl with abnormal immunity: a case report.

Project description:BackgroundTranscobalamin (TC) transports vitamin B12 from blood into cells. TC II deficiency is a rare autosomal recessive disorder. It is characterized by failure to thrive, diarrhoea, pallor, anaemia, pancytopenia or agammaglobulinemia. It is usually confirmed by molecular analysis of the TCN2 gene. We report a 2-month-old girl with two novel mutations, which were first reported in humans.Case presentationWe present a 2-month-old Chinese girl with pancytopenia, severe combined immunodeficiency disease, and megaloblastic anaemia. Targeted next-generation sequencing (NGS) was performed, which detected compound heterozygous variants in exon 7 of the TCN2 gene (Mutation 1: c.1033 C > T; Mutation 2: c.1017-1031delinsGTAACAGAGATGGTT). These mutations result in stop codons in TCN2. The c.1033C > T mutation causes a stop at codon 345 (p.Gln345Ter), and the c.1017-1031delinsGTAACAGAGATGGTT mutation causes a stop at codon 340 (p.Leu340Ter). After being diagnosed, she was treated with intramuscular 1 mg hydroxycobalamin (OH-Cbl) every day for 2 months. The CBC value returned to normal after half a month. The peripheral blood lymphocyte subsets and immunoglobulin recovered after 2 months. Then, the dosage of OH-Cbl was gradually reduced.ConclusionsTC II deficiency is a serious complication that requires lifelong treatment. Its diagnosis is difficult due to the lack of clearly identifiable symptoms. Genetic testing should be performed as early as possible if this disease is suspected. The specific observations of this case report make a considerable contribution to the literature and provide a reference for the diagnosis and treatment of future cases.

| S-EPMC7537950 | biostudies-literature

A Homozygous LAMA2 Mutation of c.818G>A Caused Partial Merosin Deficiency in a Japanese Patient.

Project description:A complete loss of merosin, which is encoded by LAMA2, causes congenital muscular dystrophy with leukoencephalopathy. Partial merosin deficiency can be caused not only by primarily LAMA2 mutations, but also secondarily by dystroglycanopathy. Although it can be molecularly diagnosed based on a genetic analysis, this method is labor-intensive because of its huge genome size. A 26-year-old male patient presented with mild muscular weakness, joint contractures, and epilepsy. Double immunofluorescence staining of a muscle biopsy specimen showed mislocalization of merosin, and a genetic analysis revealed a homozygous c.818G>A (p.Arg273Lys) mutation in LAMA2. Double immunofluorescence staining and whole exome sequencing were useful for the diagnosis of partial merosin deficiency.

| S-EPMC5891531 | biostudies-literature

Surfactant Protein B Deficiency Caused by Homozygous C248X Mutation-A Case Report and Review of the Literature.

Project description:Objective Surfactant protein B (SP-B) deficiency is a rare autosomal recessive disorder that is usually rapidly fatal. The c.397delCinsGAA mutation (121ins2) in exon 4 is found in more than two-thirds of patients. Design We report on a fatal case of SP-B deficiency caused by a homozygous C248X mutation in exon 7 of the SP-B gene. In addition, we provide an update of the current literature. The EMBASE, MEDLINE, and CINAHL databases were systematically searched to identify all papers published in the English and German literature on SP-B deficiency between 1989 and 2013. Results SP-B deficiency is characterized by progressive hypoxemic respiratory failure generally in full-term infants. They present with symptoms of respiratory distress and hypoxemia; chest X-ray resembles hyaline membrane disease. Prenatal diagnosis is possible from amniotic fluid or chorionic villi sampling. Conclusion Thirty-four mutations have been published in the literature. Treatment options are scarce. Gene therapy is hoped to be an option in the future.

| S-EPMC4502623 | biostudies-literature

Clinical Presentation and Positive Outcome of Two Siblings with Holocarboxylase Synthetase Deficiency Caused by a Homozygous L216R Mutation.

Project description:Purpose The L216R mutation, seen in individuals of Polynesian descent, is considered one of the most severe mutations associated with holocarboxylase synthetase (HLCS) deficiency and is regarded as being unresponsive to biotin. This report describes the presentation and outcome in two surviving siblings, homozygous for this highly lethal mutation. Methods and results Both cases had perinatal head imaging findings of brain hemorrhage and subependymal cysts. Both had metabolic decompensation within 24 h after birth consisting of metabolic acidosis, lactic acidosis, and thrombocytopenia. Biochemical profiles were consistent with HLCS deficiency, and genetic analysis confirmed homozygosity for the L216R mutation. After resolution of neonatal metabolic crisis, dosing of biotin was titrated on an outpatient basis to primarily control dermatitis. The eldest is currently on 1.2 g of oral biotin daily, well above any dose previously reported to treat HLCS deficiency. To date, neither patient has required hospital readmission for acute metabolic decompensation. At the age of 7, the eldest child is, to our knowledge, the oldest patient ever described in the literature who is homozygous for the L216R mutation. She has mild intellectual disability. Conclusion This report contrasts previous reports of poor outcomes and neonatal deaths in homozygous L216R patients. We also provide data on the potential upper tolerable limit of biotin. These cases suggest that the outcome of HCLS deficiency due to a homozygous L216R mutation, when diagnosed and treated early with high-level neonatal care and biotin, may not be as severe as previously reported.

| S-EPMC3897791 | biostudies-literature

"Progressive myoclonic ataxia and developmental/epileptic encephalopathy associated with a novel homozygous mutation in TCN2 gene".

Project description:BackgroundTranscobalamin II (TCN2) defect is a rare metabolic disorder associated with a range of neurological manifestations, including mild developmental delay, severe intellectual disability, ataxia, and, in some cases, seizures. Cobalamin, an essential nutrient, plays a crucial role in central nervous system myelination.Clinical presentationWe present a family with an index patient who exhibited progressive neurodevelopmental regression starting at 9 months of age, accompanied by myoclonic seizures, ataxia, and tremor. No significant hematological abnormalities were observed. Exome sequencing analysis identified a novel homozygous mutation, c.3G>A - P(Met1I), affecting the acceptor site of intron 4 of the TCN2 gene (chromosome 22: 31003321, NM_000355.4), leading to likely pathogenic variant potentially affecting translation. Following treatment with hydroxocobalamin, the patient demonstrated partial clinical improvement. He has a sibling with overt hematological abnormalities and subtle neurological abnormalities who is homozygous to the same mutation. Both parents are heterozygous for the same mutation.ConclusionsIn infants presenting with unexplained non-specific neurological symptoms, irrespective of classical signs of vitamin B12 deficiency, evaluation for TCN2 defect should be considered. Early diagnosis and appropriate management can lead to favorable outcomes.

| S-EPMC10767415 | biostudies-literature

Defective neutrophil development and specific granule deficiency caused by a homozygous splice-site mutation in SMARCD2.

Project description:BackgroundSMARCD2 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily D, member 2) has recently been shown to have a critical role in granulopoiesis in humans, mice, and zebrafish. Our patient presented with delayed cord separation, failure to thrive, and sepsis. Retrospective whole-exome sequencing confirmed a homozygous splice-site mutation in SMARCD2.ObjectiveWe sought to provide the second description of human SMARCD2 deficiency and the first functional analysis of human primary SMARCD2-deficient cells.MethodsHeparinized venous blood and bone marrow were collected from the patient after obtaining informed consent. Patient leukocytes and CD34+ cells were then isolated, phenotyped, and assessed functionally.ResultsCirculating neutrophils appeared phenotypically immature, lacking multilobed nuclei, and neutrophil granules lacked lactoferrin but showed normal levels of myeloperoxidase. Neutrophil oxidative burst was preserved in response to phorbol 12-myristate 13-acetate. Patient bone marrow-derived neutrophils and white blood cells showed a severely impaired chemotactic response. Furthermore, white blood cells showed defective in vitro killing of Staphylococcus aureus, consistent with a specific granule deficiency. Finally, patient bone marrow-derived CD34+ cells showed markedly impaired in vitro expansion and differentiation toward the neutrophil lineage. Before her molecular diagnosis, our patient underwent hematopoietic stem cell transplantation and is well 8 years later.ConclusionsThis report highlights an important role for SMARCD2 in human myelopoiesis and the curative effect of hematopoietic stem cell transplantation for the hematopoietic features of SMARCD2 deficiency.

| S-EPMC8168953 | biostudies-literature

Environmental influence on the worldwide prevalence of a 776C->G variant in the transcobalamin gene (TCN2).

Project description:BackgroundA 776C-->G variant (dbSNP ID: rs1801198) in the transcobalamin gene (TCN2; MIM# 275350) decreases the cellular and plasma concentration of transcobalamin and thereby influences the cellular availability of vitamin B(12).ObjectiveTo evaluate the worldwide prevalence of this variant and its association with homocysteine plasma level.MethodsThe study was performed in 1433 apparently healthy subjects, including Afro-Americans and Afro-Africans and in 251 Afro-Africans participants with severe malaria.ResultsThe frequencies of the 776G allele were the highest in China (0.607; 95% CI 0.554 to 0.659), low in West Africa (Bénin and Togo, 0.178; 0.154 to 0.206), and intermediate in France (0.445; 0.408 to 0.481), Italy (0.352; 0.299 to 0.409), Morocco (0.370; 0.300 to 0.447) and Mexico (0.374; 0.392 to 0.419). The 776G genotype was more frequent in Afro-Americans from New York (16.7; 8.4 to 30.7) and in Afro-African patients with severe malaria (6.0%; 95% CI 3.7 to 9.6) than in healthy Afro-African volunteers (p = 0.0004 and p = 0.033, respectively), while no difference was observed for MTHFR 677TT and 677T alleles. A disequilibrium of TCN2 genotype distribution was recorded in patients with severe malaria, with a twofold higher GG genotype than expected (p = 0.010). An association between the TCN2 polymorphism and homocysteine was observed only in Mexico and France, the two countries with the highest rate of low plasma concentration of vitamin B(12) (<100 pmol/l).ConclusionGiven the dramatic heterogeneity of the 776G allele frequency worldwide, this polymorphism may be prone to a selective pressure or confers an evolutionary advantage in confronting environmental factors, one of which is malaria.

| S-EPMC2740879 | biostudies-literature

Janus kinase 3 deficiency caused by a homozygous synonymous exonic mutation that creates a dominant splice site.

Project description: Not available

| S-EPMC5466846 | biostudies-literature

Adult male patient with severe intellectual disability caused by a homozygous mutation in the HNMT gene.

Project description:Histamine is involved in various physiological functions like sleep-wake cycle and stress regulation. The histamine N-methyltransferase (HNMT) enzyme is the only pathway for termination of histamine neurotransmission in the central nervous system. Experiments with HNMT knockout mice generated aggressive behaviours and dysregulation of sleep-wake cycles. Recently, seven members of two unrelated consanguineous families have been reported in whom two different missense HNMT mutations were identified. All showed severe intellectual disability, delayed speech development and mild regression from the age of 5 years without, however, any dysmorphisms or congenital abnormality. A diagnosis of mental retardation, autosomal recessive 51 was made. Here, we describe a severely mentally retarded adolescent male born from second cousins with a homozygous mutation in HNMT. His phenotypic profile comprised aggression, delayed speech, autism, sleep disturbances and gastro-intestinal problems. At early age, regression occurred. Treatment with hydroxyzine combined with a histamine-restricted diet resulted in significant general improvement.

| S-EPMC7735107 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data