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JIMD Reports May 2024Methionine synthase reductase deficiency (cblE) is a rare autosomal recessive inborn error of cobalamin metabolism caused by pathogenic variants in the methionine...
Late-onset refractory hemolytic anemia in siblings treated for methionine synthase reductase deficiency: A rare complication possibly prevented by hydroxocobalamin dose escalation?
Methionine synthase reductase deficiency (cblE) is a rare autosomal recessive inborn error of cobalamin metabolism caused by pathogenic variants in the methionine synthase reductase gene (). Patients usually exhibit early-onset bone marrow failure with pancytopenia including megaloblastic anemia. The latter can remain isolated or patients may present developmental delay and rarely macular dysfunction. Treatment mostly includes parenteral hydroxocobalamin to maximize the residual enzyme function and betaine to increase methionine concentrations and decrease homocysteine accumulation. We report herein 2 cblE siblings diagnosed in the neonatal period with isolated pancytopenia who, despite treatment, exhibited in adulthood hemolytic anemia (LDH >11 000 U/L, undetectable haptoglobin, elevated unconjugated bilirubin) which could finally be successfully treated by hydroxocobalamin dose escalation. There was no obvious trigger apart from a parvovirus B19 infection in one of the patients. This is the first report of such complications in adulthood. The use of LDH for disease monitoring could possibly be an additional useful biomarker to adjust hydroxocobalamin dosage. Bone marrow infection with parvovirus B19 can complicate this genetic disease with erythroblastopenia even in the absence of an immunocompromised status, as in other congenital hemolytic anemias. The observation of novel hemolytic features in this rare disease should raise awareness about specific complications in remethylation disorders and plea for hydroxocobalamin dose escalation.
PubMed: 38736634
DOI: 10.1002/jmd2.12422 -
Journal of Pediatric Endocrinology &... Apr 2024Transcobalamin II (TC) promotes the cellular uptake of cobalamin (Cbl) through receptor-mediated endocytosis of the TC-cbl complex in peripheral tissues. TC deficiency...
OBJECTIVES
Transcobalamin II (TC) promotes the cellular uptake of cobalamin (Cbl) through receptor-mediated endocytosis of the TC-cbl complex in peripheral tissues. TC deficiency is a rare disorder that causes intracellular Cbl depletion. It presents in early infancy with a failure to thrive, diarrhea, anemia, agammaglobulinemia, and pancytopenia. Data from five TC-deficient patients including clinical, biochemical, and molecular findings, as well as long-term outcomes, were collected.
CASE PRESENTATION
Mutation analysis revealed one unreported pathogenic variant in the gene. One patient had exocrine pancreatic insufficiency. We conducted a retrospective analysis of C3 and C3/C2 from dried blood samples, as this is implemented for newborn screening (NBS). We detected a marked increase in the C3/C2 ratio in two samples. Treatment was based on parenteral Cbl. Three patients treated before six months of age had an initial favorable outcome, whereas the two treated later or inadequately had neurological impairment.
CONCLUSIONS
This is the first report of Argentinean patients with TC deficiency that detected a new variant in NBS may be a tool for the early detection of TC deficiency. This data emphasizes that TC deficiency is a severe disorder that requires early detection and long-term, aggressive therapy. Accurate diagnosis is imperative, because early detection and treatment can be life-saving.
Topics: Infant, Newborn; Humans; Vitamin B 12; Transcobalamins; Retrospective Studies; Vitamin B 12 Deficiency; Anemia, Macrocytic; Amino Acid Metabolism, Inborn Errors; Early Diagnosis
PubMed: 38436354
DOI: 10.1515/jpem-2023-0577 -
European Journal of Haematology Jul 2024Having a haematological condition can adversely affect the quality of life (QoL) of family members/partners of patients. It is important to measure this often ignored...
Measurement of the major ignored burden of multiple myeloma, pernicious anaemia and of other haematological conditions on partners and family members: A cross-sectional study.
BACKGROUND
Having a haematological condition can adversely affect the quality of life (QoL) of family members/partners of patients. It is important to measure this often ignored burden in order to implement appropriate supportive interventions.
OBJECTIVE
To measure current impact of haematological conditions on the QoL of family members/partners of patients, using the Family Reported Outcome Measure-16 (FROM-16).
METHODS
A cross-sectional study, recruited online through patient support groups, involved UK family members/partners of people with haematological conditions completing the FROM-16.
RESULTS
183 family members/partners (mean age = 60.5 years, SD = 13.2; females = 62.8%) of patients (mean age = 64.1, SD = 12.8; females = 46.4%) with 12 haematological conditions completed the FROM-16. The FROM-16 mean total score was 14.0 (SD = 7.2), meaning 'a moderate effect on QoL'. The mean FROM-16 scores of family members of people with multiple myeloma (mean = 15.8, SD = 6.3, n = 99) and other haematological malignancies (mean = 13.9, SD = 7.8, n = 29) were higher than of people with pernicious anaemia (mean = 10.7, SD = 7.5, n = 47) and other non-malignant conditions (mean = 11, SD = 7.4, n = 56, p < .01). Over one third (36.1%, n = 183) of family members experienced a 'very large effect' (FROM-16 score>16) on their quality of life.
CONCLUSIONS
Haematological conditions, in particular those of malignant type, impact the QoL of family members/partners of patients. Healthcare professionals can now, using FROM-16, identify those most affected and should consider how to provide appropriate holistic support within routine practice.
Topics: Humans; Multiple Myeloma; Male; Cross-Sectional Studies; Female; Quality of Life; Middle Aged; Family; Aged; Anemia, Pernicious; Cost of Illness; Surveys and Questionnaires; Adult; Hematologic Diseases
PubMed: 38577720
DOI: 10.1111/ejh.14206