cblC type of combined methylmalonic aciduria and homocystinuria
MIM.277400 1p34.1
Autosomal recessive disease.
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
Synopsis
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)
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