Organic Acid Disorders

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Disease Name Vitamin B-12 metabolic defect with methylmalonic acidemia and homocystinuria
Alternate name(s) Combined deficiency of methylmalonyl-CoA mutase and Homocysteine
Acronym N/A
Disease Classification Organic Acid Disorder
Variants Yes
Variant name Methylmalonic acidemia, Vitamin B-12 responsive, Methylmalonic acidemia, Vitamin B-12 non-responsive
Symptom onset CblC has the earliest age of onset ranging from the first year of life to 14 years. Most patients described have been symptomatic from early in life.
Symptoms CblC disease: Early onset patients may have feeding problems, hypotonia, failure to thrive, seizures, microcephaly, developmental delay, cortical atrophy, hydrocephalus, nystagmus, pigmentary retinopathy, decreased visual acuity and bone marrow dysfunction. Late-onset patients present in childhood or adolescence with acute neurological changes including decreased cognitive performance, confusion, dementia, delirium, myelopathy and tremor. Only one late-onset patient had pigmentary retinopathy. Hematological abnormalities may also be seen in late-onset patients. They may have progressive neurological deficits in spite of appropriate treatment.
Natural history without treatment Clinical courses range from sudden death to severe psychosis and developmental delay.
Natural history with treatment

Early diagnosis and prompt institution of therapy may be the only way to change the outcome of these patients. Treatment thus far has not been successful. It is not clear that the treatment changes the natural history, but may help to decrease some of the psychiatric complications and hopefully avoid some of the skin rashes and other secondary complications such as pigmentary retinopathy and renal involvement.

Treatment Protein-restricted diet, OH-cbl supplementation, betaine treatment, carnitine supplementation.
Other N/A
Physical phenotype None special
Inheritance Autosomal recessive
General population incidence Unknown
Ethnic differences None known
Population N/A
Ethnic incidence N/A
Enzyme location CblC – precise defect not known
Enzyme Function CblC – precise defect not known
Missing Enzyme CblC – precise defect not known
Metabolite changes Methylmalonic acid and homocyteine levels are elevated in blood and urine.
Gene CblC
Gene location All gene locations are unknown.
DNA testing available No
DNA testing detail N/A
Prenatal testing Enzyme assay is available on CVS or amniocytes for known at-risk families.
MS/MS Profile Elevated C3 propionyl carnitine, elevated C4 DC methylmalonyl carnitine, ow methionine .
OMIM Link CblC:
Genetests Link
Support Group

Organic Acidemia Association

Save Babies through Screening Foundation

Genetic Alliance

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