Ocular phenotype in patients with methylmalonic aciduria and homocystinuria, cobalamin C type

Gerth, Christina; Morel, Chantal F.; Feigenbaum, Annette; Levin, Alex V.

doi:10.1016/j.jaapos.2008.06.008

Cited by 37 publications

(38 citation statements)

References 26 publications

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“…The latter patients had both been switched from IM to orally administered OHCbl supplementation and suffered late-onset neurological deterioration associated with retinopathy due to macular dysfunction [previously reported in patient 4 (Souied et al 2001)]. This retinal degeneration resembles the ophthalmologic complications reported in some patients with inherited intracellular Cbl type C defect (Gerth et al 2008). An additional TC-deficient patient has been described with retinal degeneration (Dharmasena et al 2008), which, along with neurological impairment, is possibly attributable to insufficient and/or orally administered Cbl therapy, with subsequent severe intracellular Cbl depletion and defective CNS remethylation (Hall 1992;Surtees 1998).…”

Section: Discussionmentioning

confidence: 75%

Should transcobalamin deficiency be treated aggressively?

Schiff

Baulny²,

Bard³

et al. 2010

J of Inher Metab Disea

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Transcobalamin (transcobalamin II, TC) transports plasma vitamin B(12) (cobalamin, Cbl) into cells. TC deficiency is a rare autosomal recessive disorder causing intracellular Cbl depletion, which in turn causes megaloblastic bone marrow failure, accumulation of homocysteine and methylmalonic acid, and methionine depletion. The clinical presentation reflects intracellular Cbl defects, with early-onset failure to thrive with gastrointestinal symptoms, pancytopenia, and megaloblastic anemia, sometimes followed by neurological complications. We report the clinical, biological, and molecular findings and the outcome in five TC-deficient patients. The three treated early had an initial favorable outcome, whereas the two treated inadequately had late-onset severe neuro-ophthalmological impairment. Even if the natural course of the disease over time might also result in late-onset symptoms in the aggressively treated patients, these data emphasize that TC deficiency is a severe disorder requiring early detection and probably long-term aggressive therapy. Mutation analysis revealed six unreported mutations in the TCN2 gene. In silico structural analysis showed that these mutations disrupt the Cbl-TC interaction domain and/or the putative transcobalamin-transcobalamin receptor interaction domain.

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Section: Discussionmentioning

confidence: 75%

Should transcobalamin deficiency be treated aggressively?

Schiff

Baulny²,

Bard³

et al. 2010

J of Inher Metab Disea

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“…[1][2][3][4][5] Treatment involving increased levels of methionine may restore normal rod photoreceptor sensitivity; however, this has not been shown to reverse the maculopathy or fully rescue retinal responses. 4 Ophthalmological referral is critical for these patients to ensure that their maximal visual potential is achieved.…”

Section: Commentmentioning

confidence: 99%

“…3 Given the rarity of its use in children, performing a randomised control trial is unrealistic, but an alternative method would be to establish a central database that allows clinicians who use anti-vascular endothelial growth factor therapy in children to report results and complications. …”

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confidence: 99%

Methylmalonic aciduria and homocystinuria-associated maculopathy

Francis

Rao

Rosen

2010

Eye

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exists about its metabolism and effects on development. 3 Given the rarity of its use in children, performing a randomised control trial is unrealistic, but an alternative method would be to establish a central database that allows clinicians who use anti-vascular endothelial growth factor therapy in children to report results and complications. Conflict of interestThe authors declare no conflict of interest. References

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“…Late-onset CblC patients usually present with extrapyramidal and neuropsychiatric symptoms in any decade of life (Rosenblatt et al 1997). Lateonset patients are less likely to have ocular involvement (Gerth et al 2008).…”

Section: Introductionmentioning

confidence: 99%

Cobalamin C Disease Missed by Newborn Screening in a Patient with Low Carnitine Level

et al. 2015

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Cobalamin C (CblC) disease is the most common inherited disorder of intracellular cobalamin metabolism. It is a multisystemic disorder mainly affecting the eye and brain and characterized biochemically by methylmalonic aciduria, low methionine level, and homocystinuria. We report a patient found to have CblC disease who initially presented with low carnitine and normal propionylcarnitine (C3) levels on newborn screen. Newborn screening likely failed to detect CblC in this patient because of both his low carnitine level and the presence of a mild phenotype.

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Ocular phenotype in patients with methylmalonic aciduria and homocystinuria, cobalamin C type

Cited by 37 publications

References 26 publications

Should transcobalamin deficiency be treated aggressively?

Should transcobalamin deficiency be treated aggressively?

Methylmalonic aciduria and homocystinuria-associated maculopathy

Cobalamin C Disease Missed by Newborn Screening in a Patient with Low Carnitine Level

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