The adolescent and adult form of cobalamin C disease: clinical and molecular spectrum.
BACKGROUND
Cobalamin C disease is the most common inborn error of cobalamin metabolism with an autosomal recessive mode of inheritance and mutations within the MMACHC gene. Clinical features, including systemic, haematological and neurological abnormalities, usually occur in the first year of life. Adolescent and adult onset presentations are rare.


METHODS
We report on the clinical, molecular and imaging features in three patients aged 40, 42 and 42 years at the last follow-up. We examine these cases together with eight previously described cases to determine the clinical and molecular features of the disease in adults.


RESULTS
Mean age at onset of clinical symptoms was 26 years; clinical features included predominant neurological disturbances and thromboembolic complications. White matter abnormalities on brain MRI were sometimes observed. Most patients (eight of nine patients investigated) were compound heterozygotes for the 271dupA mutation and a missense mutation. Intramuscular or intravenous hydroxycobalamin therapy stopped the progression of the disease and resulted in a better clinical outcome and favourable biological status in 7/9 treated cases, while the two untreated patients died quickly.


CONCLUSIONS
As cobalamin C disease and related disorders of homocysteine metabolism are treatable conditions, homocysteinaemia should be included in the investigations of patients with progressive neurological deterioration, unexplained psychiatric disturbances or recurrent thromboembolic events.
Thauvin-Robinet
C
C
Centre de Génétique, Hôpital d'Enfants, 10 Bd maréchal de Lattre de Tassigny, 21034 Dijon Cedex, France. christel.thauvin@chu-dijon.fr
Roze
E
E
Couvreur
G
G
Horellou
M-H
MH
Sedel
F
F
Grabli
D
D
Bruneteau
G
G
Tonneti
C
C
Masurel-Paulet
A
A
Perennou
D
D
Moreau
T
T
Giroud
M
M
de Baulny
H Ogier
HO
Giraudier
S
S
Faivre
L
L
D000293:Adolescent; D000328:Adult; D000592:Amino Acid Metabolism, Inborn Errors / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D001921:Brain / Q000473:pathology; D020739:Brain Diseases, Metabolic, Inborn / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002552:Cerebral Ventricles / Q000473:pathology; D002869:Chromosome Aberrations; D004252:DNA Mutational Analysis; D005260:Female; D005500:Follow-Up Studies; D020440:Gene Duplication; D005808:Genes, Recessive / Q000235:genetics*; D006580:Genetic Carrier Screening; D006712:Homocystinuria / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D006879:Hydroxocobalamin / Q000008:administration & dosage; D007262:Infusions, Intravenous; D007273:Injections, Intramuscular; D008279:Magnetic Resonance Imaging; D008297:Male; D008764:Methylmalonic Acid / Q000652:urine*; D020125:Mutation, Missense; D009460:Neurologic Examination / Q000187:drug effects; D010088:Oxidoreductases; D013116:Spinal Cord / Q000473:pathology
D002352:Carrier Proteins; D008764:Methylmalonic Acid; C508359:MMACHC protein, human; D010088:Oxidoreductases; D006879:Hydroxocobalamin