Vitamin B12 Optic Neuropathy in Autism

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Vitamin B

₁₂

Optic Neuropathy in Autism

abstract

Dietary vitamin B₁₂deficiency was identified as a cause of partially reversible optic neuropathy in 3 autistic children. All of the affected children presented with gradual visual loss. Examination revealed op-tic atrophy, and further questioning regarding diet revealed that all 3 children had severe food selectivity and highly stereotyped diets that resulted in an almost total lack of animal products in their diets. Vita-min B₁₂levels were low in all 3 children. Treatment with intramuscular vitamin B₁₂and normalization of vitamin B₁₂levels resulted in improve-ment of visual functioning in all 3 children. These cases illustrate that food selectivity, a known complication of autism, can result in vitamin deficiency that can cause visual loss and optic atrophy. Physicians must have a high index of suspicion when evaluating children with autism and visual loss to detect this rare cause of optic atrophy. Pediatrics2010;126:e967–e970

AUTHORS:Stacy L. Pineles, MD, Robert A. Avery, DO, and Grant T. Liu, MD

Neuro-ophthalmology Service, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania; and Division of Neuro-ophthalmology, Departments of Neurology and Ophthalmology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

KEY WORDS

autism, dietary patterns, visual impairment www.pediatrics.org/cgi/doi/10.1542/peds.2009-2975 doi:10.1542/peds.2009-2975

Accepted for publication Jun 10, 2010

Address correspondence to Grant T. Liu, MD, Division of Neuro-Ophthalmology, Hospital of the University of Pennsylvania, 3400 Spruce St, Philadelphia, PA 19104. E-mail:

[email protected]

FINANCIAL DISCLOSURE:The authors have indicated they have no ﬁnancial relationships relevant to this article to disclose.

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According to some reports, there has been a dramatic increase in the prev-alence of autism within the past de-cade from⬃1 in 2500 children in the 1980s to the current estimate of⬃1 in 110 children.1,2_{Autism is characterized}

by a spectrum of abnormal behaviors including impaired social interaction, communication difﬁculties, and ste-reotyped patterns of interests and ac-tivities.3_{In addition, autism has been}

associated with several disorders of higher-order visual perception, as well as an increased prevalence of ocular motility disorders.4 _{In addition, there}

have been numerous associations be-tween autism and feeding difﬁculties, most commonly with patients who as-sume highly stereotyped diets and refuse all foods except those of a cer-tain color or texture.5,6 _Reported

se-quelae of diet-related vitamin deﬁcien-cies in autistic patients include rickets,7 _scurvy,8 _{and vitamin A}

deﬁ-ciency–related xerophthalmia.9–12

Be-cause vitamin B₁₂deﬁciency is a well-known cause of nutritional optic neuropathy,13 _{it follows that autistic}

children whose stereotyped diets do not include any animal products may be at risk for vision loss from B₁₂ deﬁ-ciency–related optic atrophy. Herein we report the cases of 3 such patients, all of whom presented with vision loss and optic atrophy that resulted from vitamin B₁₂ deﬁciency secondary to highly limited diets.

CASE REPORTS

Case 1

A 6-year-old autistic boy presented with a 1-month history of decreased visual acuity. His parents noted that he could previously see objects well at a distance and near, but he had recently begun to hold objects very close and appeared to use his peripheral vision to view objects. There was no family history of ophthalmologic or neuro-logic disease. On examination, his

Teller visual acuity (preferential look-ing test) was 20/130 bilaterally under photopic conditions. He appeared to grope for toys. His pupils, ocular motility, ocular alignment, and ante-rior segment examinations were nor-mal. Cycloplegic refraction was not performed. A posterior segment exam-ination revealed bilateral optic atro-phy. Because of poor cooperation, we were unable to perform color vision, stereoacuity, or formal visual ﬁeld testing.

After further questioning, his parents noted that his diet consisted primarily of bagels, cereal, and French fries; he ate no meat. A brain MRI, Lyme titers, and erythrocyte sedimentation rate were all normal. Laboratory evaluation revealed a vitamin B₁₂level of ⬍150 pg/mL (normal: 245–1078 pg/mL), ho-mocysteine level of 6.25␮mol/L (nor-mal: 0.8 – 6.5 ␮mol/L), methylmalonic acid level of 1781 ␮mol/L (normal: 145–345␮mol/L), and a normal hemo-globin level. His vitamin A level was also found to be subnormal at 14 pg/mL (normal: 26 –72 pg/mL), but results of electroretinography were normal. A formal gastrointestinal eval-uation, including evaluation of anti– parietal cell antibody levels, did not reveal a nondietary cause for his vita-min A and B₁₂deﬁciencies. Treatment with intramuscular vitamin B₁₂ was commenced, and, with normalization of his vitamin B₁₂(2150 pg/mL), homo-cysteine (6.25␮mol/L), and methylma-lonic acid (158␮mol/L) levels, his vi-sual behavior improved such that he was able to reach directly for objects instead of groping as he had done in the past. Repeat Teller visual acuity testing was attempted but not performed be-cause of a lack of cooperation.

Case 2

A 13-year-old autistic boy presented with gradual vision loss over 6 months. His parents stated that his visual

be-havior had previously been normal, but he had recently begun bumping into walls and tripping over objects on the floor. There was no family history of ophthalmologic or neurologic dis-ease. On examination, he did not fix, follow, or blink to threat. He did, how-ever, grimace to light under scotopic and photopic conditions. His pupils, oc-ular motility, ococ-ular alignment, and an-terior segment were normal. Cyclople-gic refraction revealed mild hyperopia. Posterior segment examination re-vealed bilateral optic atrophy. Because of poor cooperation, we were unable to obtain exact visual acuity, color vi-sion, stereoacuity, or formal visual field testing.

After further questioning, his parents noted that his diet consisted mainly of potatoes, fruit, and bagels and that he had a remote history of low vitamin A and B₁₂ levels. He had been treated previously with intramuscular vitamin B₁₂for a 2-month period 5 years before this presentation. Laboratory test re-sults from 3 months before his presen-tation were significant for a low-normal vitamin B₁₂level (297 pg/mL) and subnormal vitamin A level (2 pg/mL). Results of brain MRI were normal. Repeat testing revealed a vitamin B₁₂ level of 195 pg/mL (low), methylma-lonic acid level of 2082␮mol/L (high), and homocysteine level of 4.8␮mol/L (normal). Repeat testing also revealed a normal vitamin A level (61 pg/mL), and results of electroretinography were also normal. A formal gastroin-testinal evaluation, including measur-ing anti–parietal cell antibody levels, did not reveal a nondietary cause for his B₁₂deficiency. The patient also was found to have a mild normocytic ane-mia. Vitamin B₁₂ treatment was initi-ated, and the child’s visual behavior subjectively improved such that he no longer bumped into walls, and he was able to step over objects on the floor after normalization of the B₁₂ (801

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pg/mL), homocysteine (3.82 ␮mol/L), and methylmalonic acid (235␮mol/L) levels.

Case 3

A 7-year-old autistic boy presented with a 6-week history of changing vi-sual behavior. His vision was previ-ously normal, but he had recently be-gun to have difﬁculty navigating in familiar areas and started groping for objects. There was no family history of ophthalmologic or neurologic disease. On examination, he did not ﬁx, follow, or blink to threat. His pupil examina-tion, ocular motility, ocular alignment, and anterior segment examinations were normal. Cycloplegic refraction revealed mild hyperopia. Posterior segment examination revealed bilat-eral optic atrophy.

After further questioning, his parents noted that his diet consisted primarily of French fries and occasionally pro-cessed chicken nuggets. An MRI re-vealed an abnormal signal in the right sphenoid bone, which was not contig-uous with the optic canal and was thought to be a developmental anom-aly. The MRI was otherwise normal. A lumbar puncture revealed an elevated opening pressure but normal cerebro-spinal ﬂuid constituents. The elevated opening pressure was not thought to be related to his optic atrophy, be-cause the optic atrophy was not con-sistent with the expected gliotic ap-pearance of a chronically edematous optic nerve. His vitamin B₁₂level was 155 pg/mL (low), homocysteine level was 15.7 ␮mol/L (high), and methyl-malonic acid level was 512 ␮mol/L (high). His vitamin A levels were within normal limits. Formal gastrointestinal evaluation revealed mild gastric ul-cers. Results of anti–parietal cell anti-body testing were negative. Electro-retinographic testing results were within normal limits. Vitamin B₁₂ injec-tions were initiated, and his B₁₂level

was normalized (1065 pg/mL) (repeat homocysteine and methylmalonic acid measurements were not obtained). Subjective improvement in his visual behavior was noted, such that he was able to name objects held within 1 ft.

DISCUSSION

These 3 cases are, to the best of our knowledge, the first reported cases of vision loss and optic atrophy second-ary to vitamin B₁₂deficiency related to poor diet in autistic children. All 3 chil-dren presented with gradual changes in visual behavior but were unable to convey verbally the features of their vi-sual loss. All of their examinations were limited but showed optic atrophy. When further questioned about their child’s diet, all 3 sets of parents re-ported a highly stereotyped and poor diet that was lacking in meats and dairy products. Parents of autistic chil-dren often report feeding difficulties that range from selective food behav-iors to outright food refusal.14_Children

who refuse foods from animal sources, such as meat and dairy products, are speciﬁcally at higher risk for vitamin B₁₂ deﬁciency.

Although B₁₂deﬁciency is a rare cause of optic neuropathy, it is most com-monly reported in individuals with per-nicious anemia or those who have un-dergone complete or partial removal of the ileum. The pathogenesis of B₁₂ deﬁciency optic neuropathy has been shown in a primate model to be the result of demyelination of the papillo-macular bundle, possibly secondary to cyanide build-up or improper fatty acid synthesis.15,16

There are several etiologies of gradual vision loss with optic atrophy that also need to be considered in these cases. Neuroimaging is required to rule out a compressive mass. In addition, one can consider a laboratory workup for nutritional deﬁciencies, genetic condi-tions, or other metabolic diseases,

in-fectious etiologies, and vasculitic pro-cesses. Although none of our patients demonstrated the expected macro-cytic anemia associated with B₁₂ deﬁ-ciency, neurologic sequelae of B₁₂ de-ﬁciency without anemia can occur, especially with coexistent elevations in methylmalonic acid and homocysteine levels.17

To date, there have been a few reports of dietary vitamin deficiencies in pa-tients with autism that caused visual loss. However, these cases have all in-volved vitamin A deficiency, and the ophthalmic findings were heavily weighted toward anterior segment abnormalities.9–12_{There has been 1}

re-port of optic atrophy that was pre-sumed secondary to vitamin A deﬁ-ciency.10 _{Unlike our patients, this}

patient had coexistent xerophthalmia and xerostomia, which prompted test-ing of the vitamin A level; however, vi-tamin A is not a usual cause of primary optic atrophy without coexistent con-junctival, corneal, or retinal disease. Our 2 patients who had coexistent de-creased vitamin A levels had normal electroretinograms, which makes it unlikely that deﬁciency of that vitamin contributed to the visual loss.

CONCLUSIONS

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have a high index of suspicion for vita-min deﬁciencies as an etiology of vi-sual impairment in children with au-tism; questions about diet should be

part of routine history-taking in this population, and a careful fundus exam-ination to rule out optic atrophy should always be performed. In our

experi-ence, B₁₂deﬁciency optic neuropathy in autism is a recognizable, highly treatable, and at least partially revers-ible disorder.

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DOI: 10.1542/peds.2009-2975 originally published online September 20, 2010;

2010;126;e967

Pediatrics

Stacy L. Pineles, Robert A. Avery and Grant T. Liu

Optic Neuropathy in Autism

12 Vitamin B

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DOI: 10.1542/peds.2009-2975 originally published online September 20, 2010;

2010;126;e967

Pediatrics

Stacy L. Pineles, Robert A. Avery and Grant T. Liu

Optic Neuropathy in Autism

12 Vitamin B

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