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Methylmalonic acidemia with homocystinuria, type cblC

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Disease definition

cblC type methylmalonic acidemia with homocystinuria is a form of methylmalonic acidemia with homocystinuria, an inborn error of vitamin B12 (cobalamin) metabolism characterized by megaloblastic anemia, lethargy, failure to thrive, developmental delay, intellectual deficit and seizures.

ORPHA:79282

Classification level: Subtype of disorder

Synonym(s):
  • CblC defect
  • Cobalamin C defect
  • Combined defect in adenosylcobalamin and methylcobalamin synthesis, type cblC
  • Methylmalonic aciduria with homocystinuria, type cblC

Prevalence: Unknown

Inheritance: Autosomal recessive

Age of onset: All ages

ICD-10: D58.8

ICD-11: 5C50.E0

OMIM: 277400

UMLS: C1848561

Summary
Epidemiology

To date, over 500 cases of cblC have been reported, making it the most frequent type of methylmalonic acidemia with homocystinuria.

Clinical description

The disease typically presents with failure to thrive, acute neurological deterioration, intellectual deficit, lethargy, seizures, microcephaly, a salt-and-pepper retinopathy, and signs of megaloblastic anemia (pallor, fatigue, anorexia). Severe brain abnormalities including hydrocephalus, white matter abnormalities, cerebral atrophy, and unusual basal ganglia lesions are common. Onset of the disorder can be early (infantile) or late (juvenile or adult), with the late-onset form characterized by ataxia, dementia and psychosis.

Etiology

cblC type methylmalonic acidemia with homocystinuria is caused by mutations in the MMACHC gene (1p36.3) and is transmitted in an autosomal recessive manner.

Last update: March 2012 - Expert reviewer(s): Dr David ROSENBLATT
A summary on this disease is available in Français, Español, Deutsch, Italiano, Português, Nederlands Polski
Detailed information

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General public
Guidelines
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Anesthesia guidelines
English (2017) - Orphananesthesia
Čeština (2017) - Orphananesthesia
Clinical practice guidelines
English (2024) - Kidney Int Rep
English (2025) - Kidney Int Rep
English (2021) - J Inherit Metab Dis Logo ERN
English (2017) - Haematologica Logo ERN
English (2014) - Orphanet J Rare Dis
Diagnostic Keys
Français (2025) - Les clés du diagnostic Logo FSMR
Disease review articles
Clinical genetics review
English (2021) - GeneReviews
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