Clinicopathologic Reports, Case Reports, and Small Case Series
July 2001

Retinal Degeneration Associated With Congenital Transcobalamin II Deficiency

Author Affiliations

Copyright 2001 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.2001

Arch Ophthalmol. 2001;119(7):1076-1077. doi:

Transcobalamin II (TCII) is a cobalamin (Cbl)-binding plasma protein that promotes the cellular uptake of Cbl (vitamin B12) by many tissues. Transcobalamin II deficiency is a rare autosomal recessive disorder.1

Report of a Case

A girl, born to healthy nonconsanguineous parents, was seen at age 3 months with pallor, lethargy, failure to thrive, and hypotonia. At age 7 months, she was seen by a physician because of pallor, purpura, hypotonia, myoclonia, epileptiform episodes of blinking, and chronic upper respiratory infections. Her blood cell count revealed severe pancytopenia. Serum Cbl levels were in the low to normal range. Methylmalonyl aciduria and homocystinuria were detected. The total unsaturated Cbl binding capacity of serum, measured as previously described,2 was 48 pmol/L (reference range, 440-880 pmol/L), without binding of [57Co]Cbl to TCII. Immunoreactive TCII serum levels were 95 pmol/L (reference, >370 pmol/L). Culture findings from the patient's fibroblasts incubated with 35S-methionine expressed immunoreactive radio-labeled TCII with the same molecular weight as native TCII, but no Cbl-binding TCII was secreted into the culture medium. The patient was treated with intramuscular cyanocobalamin, 1000 µg every 10 days for 1 year, and subsequently with oral cyanocobalamin (1000 µg per day) and oral folic acid until age 16 years.

At age 13 years, she was seen for headaches, lipothymia, epileptiform myoclonic episodes, cerebellar dysfunction, impairment of the pyramidal track, and was found to be moderately retarded. There were no ocular abnormalities. However, at age16 years, she complained of a decrease in visual acuity, found to be 20/30 OU. Findings from fundus examination revealed a dark oval in the macula, surrounded by a ring of hypopigmentation. These findings were bilateral and symmetrical. The peripheral fundus examination showed a diffuse area of salt and pepper retinopathy associated with rare bone spicule formation (Figure 1). Fluorescein angiography showed an ovoid zone of hypofluorescence in the macula surrounded by a diffuse hyperfluorescence (Figure 1). Indocyanine green angiography findings are shown in Figure 2. Visual field analysis demonstrated bilateral annular perifoveal scotomata. Electroretinogram analysis showed decreased amplitude of both A and B waves. The patient was then started on intramuscular hydroxocobalamin (5000 µg 3 times per week). The episodes of myoclonia and the cordonal posterior pyramidal signs decreased, as did the methylmalonyl aciduria and homocystinuria. At age 19 years, best-corrected visual acuity, visual field analysis, electroretinogram recording, and fluorescein and indocyanine green angiographies remained unchanged.

Figure 1.
Image not available

A, A dark oval area is observed in the central macula, surrounded by a ring of hypopigmentation. The periphery of the fundus shows a diffuse area of salt-and-pepper retinopathy associated with peripheral bone spicule formations. B, At 26 seconds, a diffuse salt-and-pepper appearance was observed in the whole posterior pole, suggesting association of window defect and pigmentary mottling. The central macula remained profoundly hypofluorescent during the sequence.

Figure 2.
Image not available

A, At the early phase, a blockage of the deep choroidal fluorescence was observed in the central macula (white arrows). B, Hypofluorescent dots, scattered in the pericentral area, were observed only on late phase of indocyanine green angiography.


The retinal findings in this patient support the diagnosis of "unusual" pigmentary retinopathy, with salt-and-pepper fundi. A peculiar bilateral brown macular ovoid zone was observed, which was hypofluorescent on fluorescein and indocyanine green angiographic studies. This retinal degeneration may be similar to the ophthalmologic complications reported in some patients with the inherited Cbl deficiency. Indeed, 5 patients with inherited Cbl deficiency and a similar retinopathy to that described in our patient have been reported, but most of them died in infancy.1,3,4

To our knowledge, this is the first report of retinal dystrophy associated with congenital TCII deficiency. It is notable that while the patient was receiving high doses of intramuscular hydroxocobalamin supplementation, no progression of retinal degeneration was observed.

Corresponding author and reprints: Gisèle Soubrane, PhD, CliniqueOphtalmologique, Universitaire de Créteil, 40 avenue de Verdun, 94010 Créteil, France (e-mail:

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