Abstract
Background
Inborn errors of cobalamin (Cbl) absorption and metabolism form a large group of rare diseases that include Cbl-C disorder. Among the renal complications of Cbl-C disorder, atypical hemolytic uremic syndrome (HUS) is the least common and has been described only in a small number of cases.
Case-diagnosis/Treatment
Four patients were admitted to our clinic after 15–30 days of life with vomiting associated with poor sucking, failure to thrive, lethargy and hypotonia. Examinations showed thrombocytopenia and microangiopathic hemolytic anemia associated with renal damage. The neonates had high blood homocysteine levels, increased urinary levels of both homocystine and methylmalonic acid, increased propionylcarnitine (C3) levels and an increased C3/acetylcarnitine ratio. Homozygosity for c.271-272dupA (p.Arg91LysfsX14) of the MMACHC gene was detected in three patients, and heterozygosity for c.271-272dupA and c.666C > A(p.Tyr222X) in one patient, which confirmed the diagnosis of Cbl-C disorder. Treatment with parenteral hydroxycobalamin in combination with folic acid and betaine gradually normalized the metabolic test findings and hematological and renal parameters after about 1 week.
Conclusions
Atypical HUS in neonates with Cbl-C disorder may be associated with mild to moderate renal involvement also in early-onset disease, and early adequate therapy can reverse renal damage.
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Acknowledgments
We are grateful to the patients and their parents. Our sincere thanks go to the staff following up these patients: Fabio Mosca and Lorenza Pugni (neonatologists); Nicola Principi and Marta Cerutti (pediatricians); Faustina Lalatta and Donatella Milani (geneticists); Alberto Edefonti, Gianluigi Ardissino and Mirko Berlinghieri (pediatric nephrologists); Giovanna Chidini and Cristiano Gandini (pediatric intensive care unit specialists); Silvia Osnaghi (ophthalmologist); Mariella Galli (pediatric cardiologist); Paola Vizziello (neuropsychiatrist); Simona Salera (dietitian). We are also grateful to Carlo Corbetta and Katia Cavicchi for performing the laboratory studies.
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Menni, F., Testa, S., Guez, S. et al. Neonatal atypical hemolytic uremic syndrome due to methylmalonic aciduria and homocystinuria. Pediatr Nephrol 27, 1401–1405 (2012). https://doi.org/10.1007/s00467-012-2152-6
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DOI: https://doi.org/10.1007/s00467-012-2152-6