Related Experiment Videos
Cobalamin disorder Cbl-C presenting with late-onset thrombotic microangiopathy
Johan L K Van Hove1, Rita Van Damme-Lombaerts, Stephanie Grünewald
1Department of Pediatrics, University Hospital Gasthuisberg, Katholieke Universiteit Leuven, Leuven, Belgium. Johan.Vanhove@uz.kuleuven.ac.be
Insights
This study identifies a rare genetic disorder causing kidney disease and anemia in siblings. Prompt diagnosis and treatment with hydroxycobalamin can significantly improve patient outcomes.
Area of Science:
- Genetics
- Nephrology
- Biochemistry
Background:
- A 12-year-old boy and his 4-year-old sister presented with proteinuria, hematuria, hypertension, and chronic hemolytic anemia.
- The boy experienced severe hypertensive encephalopathy and transient renal failure at age 13.
Observation:
- Renal biopsy revealed chronic thrombotic microangiopathic nephropathy.
- Both siblings exhibited hyperhomocysteinemia and mild methylmalonic aciduria.
- Fibroblast analysis indicated a defect in cobalamin metabolism, consistent with the Cbl-C complementation group.
Findings:
- Parenteral hydroxycobalamin therapy normalized homocysteine levels and resolved methylmalonic aciduria.
- Combined hydroxycobalamin and betaine treatment further reduced homocysteine levels.
- Treatment halted hemolysis, resolved hematuria, normalized proteinuria, and stabilized creatinine clearance.
Implications:
- This case highlights an unusual but treatable cause of thrombotic microangiopathy.
- Testing for this disorder is recommended for patients with chronic thrombotic microangiopathy, irrespective of age.
- Early diagnosis and intervention with hydroxycobalamin can prevent severe complications and improve renal function.
Abstract:
Two siblings, a boy age 12 and his sister age 4 years, presented with proteinuria and hematuria, hypertension, and chronic hemolytic anemia. At age 13 years, the boy developed an episode of severe hypertensive encephalopathy and transient renal failure. Both children are attending normal school, have no neurologic symptoms, and only minimal pigmentary retinal abnormalities. Renal biopsy showed a chronic thrombotic microangiopathic nephropathy. Both patients had hyperhomocysteinemia and mild methylmalonic aciduria. Fibroblasts showed decreased cobalamin uptake, reduced methyl- and adenosyl-cobalamin formation, and deficient incorporation of formate and propionate, compatible with the Cbl-C complementation group, but milder than that found in cells from most patients. Both patients and their father carry a balanced reciprocal translocation. Parenteral hydroxycobalamin treatment reduced the homocysteine levels, and methylmalonic acid disappeared. Increasing the dosage of hydroxycobalamin from 1 to 2.5, then 5 mg daily together with betaine, further reduced homocysteine levels (boy from 118 to 23 microM and girl from 59 to 14 microM). With this treatment, hemolysis has stopped, hematuria has disappeared, proteinuria has almost normalized, and creatinine clearance has been stable. Investigations for chronic thrombotic microangiopathy should include testing for this unusual but treatable disorder, regardless of age of presentation.