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cblC type of combined methylmalonic aciduria and homocystinuria

MIM.277400 1p34.1

Thursday 2 February 2006

Definition: Autosomal recessive disease of cobalamine deficiency.

Synopsis

- Onset usually in first year of life
- Childhood onset also reported
- Early-onset associated with more severe course and early death
- Variable response to vitamin B12 therapy
- failure to thrive
- microcephaly
- hydrocephalus
- long face
- high forehead
- flat philtrum
- low-set ears
- large, floppy ears
- retinitis pigmentosa
- nystagmus
- decreased visual acuity
- vascular lesions
- thrombotic microangiopathy
- thromboembolism
- poor feeding
- renal failure
- hemolytic-uremic syndrome
- thrombotic microangiopathic nephropathy
- hypotonia
- lethargy
- developmental delay
- mental retardation
- seizures
- cortical atrophy
- acute neurologic decompensation (in later-onset cases)
- decreased cognition (later-onset)
- confusion (later-onset)
- dementia (later-onset)
- delirium (later-onset)
- extrapyramidal symptoms (later-onset)
- tremor (later-onset)

Laboratory

- metabolic acidosis
- megaloblastic anemia
- thrombocytopenia
- anemia
- neutropenia
- homocystinuria
- homocystinemia
- methylmalonic aciduria
- methylmalonic acidemia
- decreased serum methionine
- cystathioninemia
- cystathioninuria
- uremia
- hematuria
- proteinuria
- decreased methylmalonyl-CoA mutase (MUT, 609058) activity
- decreased methionine synthase (MTR, 156570) activity
- decreased adenosylcobalamin (AdoCbl)
- decreased methylcobalamin (MeCbl)
- normal serum cobalamin
- decreased cobalamin in liver, kidney, and cultured fibroblasts

Etiology

- cblC type of combined methylmalonic aciduria and homocystinuria is caused by mutation in gene MMACHC (MIM.609831)at 1p34.1

References

- Russo P, Doyon J, Sonsino E, Ogier H, Saudubray JM. A congenital anomaly of vitamin B12 metabolism: a study of three cases. Hum Pathol. 1992 May;23(5):504-12. PMID: 1568746