Blindness Caused by a Junk Food Diet
Background: Popular media have highlighted the risks for poor cardiovascular health, obesity, and cancer associated with junk food, but poor nutrition can also permanently damage the nervous system, particularly vision.
Objective: To alert clinicians of visio risks associated with a diet restricted to junk food.
Case Report: A 14-year-old boy presented to his family practitioner with tiredness. He was a “fussy eater” but was otherwise well and took no medications. Tests found macrocytic anemia and low vitamin B12 level but no antibodies to intrinsic factor or tissue transglutaminase. He was treated with vitamin B12 injections and dietary advice.
At age 15 years, he developed sensorineural hearing loss and was referred to an otolaryngologist. Magnetic resonance imaging (MRI) showed no structural abnormalities. Shortly afterward, he developed vision symptoms. Findings of a slit-lamp examination by an ophthalmologist were normal. No cause was found.
At age 17 years, he was referred to a neuro-ophthalmologist after 2 years of progressive vision loss. Findings were consistent with optic neuropathy: Visual acuity was 20/200 bilaterally, he read 8 of 17 Ishihara color plates with either eye, pupil responses and slit-lamp examination findings were normal, and he had bilateral central visual field defects and loss of retinal nerve fibers affecting the optic discs temporally and maculopapillar bundles. There were delayed P100 responses in visual evoked potentials with normal amplitudes (Figure). He had brisk reflexes, but findings of a neurologic examination were otherwise normal.
Top. Results of Goldmann perimetry showing bilateral central visual field loss (“blind spots”) in both eyes. The blue lines depict the results using the I4e target, and the red lines depict the results using the I2e target (dimmer). The hatched blue areas plot the physiologic blind spots, and the hatched red areas plot the central visual field defects using the I2e target. Bottom. Optical coherence tomography measurements showing temporal thinning of the patient's retinal nerve fiber layer surrounding the optic nerve heads. Associated retinal thinning was seen in the region of the maculopapillar bundles. Slit-lamp examination showed unremarkable optic nerve appearances. The color key is for comparison of the patient's data with the general population. Green indicates 5% to 95% of the general population, and red and yellow indicate data outside the normal range.
Gadolinium-enhanced MRI showed no compressive or inflammatory lesions. Results of genetic tests for Leber hereditary optic neuropathy were negative. Laboratory evaluation showed persistent macrocytosis with normal ferritin, folate, and vitamin B12 levels; thyroid function; and liver function (Table). However, homocysteine and methylmalonic acid levels were elevated, indicating functional vitamin B12 deficiency.
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The patient's functional vitamin B12 deficiency prompted further investigation of his nutrition. He denied use of alcohol, tobacco, or drugs. Height and weight were average (172.9 cm and 65.7 kg, respectively) and body mass index (BMI) was normal (22 kg/m2). However, the patientconfessed that, since elementary school, he would not eat certain textures of food. He had a daily portion of fries from the local fish and chip shop and snacked on Pringles (Kellogg), white bread, processed ham slices, and sausage. His vitamin B12 injections had lapsed. He had low copper and selenium levels, a high zinc level, and markedly reduced vitamin D level and bone mineral density. Results of gastrointestinal biopsies and Fibroscan were normal.
He was prescribed nutritional supplements that corrected his deficiencies and was referred to mental health services for his eating disorder. His vision stabilized but did not improve.
Discussion: Nutritional optic neuropathy is usually caused by malabsorption, drugs, or poor diet combined with alcoholism and/or smoking. Purely dietary causes are rare in developed countries. Deficiencies in vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (niacin), vitamin B6 (pyridoxine), vitamin B9 (folate), vitamin B12 (cobalamin), and copper are known mechanisms (1, 2). However, in many centers, availability of these tests is limited, so multiple deficiencies are assumed in patients with consistent clinical features and at least 1 confirmed deficiency.
All of these likely contributed to the patient's vision and hearing loss (vitamin D deficiency probably contributed to his osteopenia), but they remained undiagnosed for several years. The patient's history of treated vitamin B12 deficiency and low-normal vitamin B12 level likely contributed to the delayed diagnosis. Reliability of the vitamin B12 test is assay-dependent; is confounded by intrinsic factor antibodies; and varies in the lower range, when homocysteine and methylmalonic acid levels are more sensitive indicators of functional vitamin B12 deficiency (3). Neurologic dysfunction from vitamin B12 deficiency is worse in patients with higher hematocrits (3). Copper deficiency caused by gastric malabsorption, but not poor nutrition, has been reported to cause optic neuropathy, myelopathy, and macrocytosis (2).
Junk foods are nutritionally poor but energy-dense and cheap. Hence, high-energy diets correlate with high BMI, low socioeconomic status, and poor health (4). “Fussy eating” that is restricted to junk foods and causes multiple nutritional deficiencies is an eating disorder. Avoidant-restrictive food intake disorder is a relatively new diagnostic entity, but unlike anorexia nervosa, it is not driven by weight or shape concerns. Onset is in middle childhood, with lack of interest in food, heightened sensitivity to food textures, and fear of the consequences of eating (5). As in this patient, BMI is often normal.
Nutritional optic neuropathy should be considered in any patient with unexplained vision symptoms and poor diet, regardless of BMI. It is important to note that nutritional optic neuropathy is potentially reversible if caught early. If left untreated, it leads to permanent blindness.
References
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Grzybowski A ,Zülsdorff M ,Wilhelm H ,et al . Toxic optic neuropathies: an updated review. Acta Ophthalmol. 2015;93:402-10. [PMID:25159832 ] doi:10.1111/aos.12515 CrossrefMedlineGoogle Scholar - 2.
Pineles SL ,Wilson CA ,Balcer LJ ,et al . Combined optic neuropathy and myelopathy secondary to copper deficiency. Surv Ophthalmol. 2010;55:386-92. [PMID:20451943 ] doi:10.1016/j.survophthal.2010.02.002 CrossrefMedlineGoogle Scholar - 3.
Stabler SP . Clinical practice. Vitamin B12 deficiency. N Engl J Med. 2013;368:149-60. [PMID:23301732 ] doi:10.1056/NEJMcp1113996 CrossrefMedlineGoogle Scholar - 4.
Darmon N andDrewnowski A . Contribution of food prices and diet cost to socioeconomic disparities in diet quality and health: a systematic review and analysis. Nutr Rev. 2015;73:643-60. [PMID:26307238 ] doi:10.1093/nutrit/nuv027 CrossrefMedlineGoogle Scholar - 5.
Mairs R andNicholls D . Assessment and treatment of eating disorders in children and adolescents. Arch Dis Child. 2016;101:1168-75. [PMID:27381185 ] doi:10.1136/archdischild-2015-309481 CrossrefMedlineGoogle Scholar
This article was published at Annals.org on 30 September 2019.
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Low copper is diagnostic of deficiency according the Oxford Textbook of Medicine (2, 3). This deficiency may explain some seemingly unrelated phenomena that have been reviewed (2-5).
Decreased myelination of optic nerves has been found in copper deficient rodents(5). Rats, mice and people low in copper have poor hearing; a patient with hearing loss improved with a copper supplement (4). There can be no medical doubt that copper deficiency can cause osteoporosis in people; two double-blind, placebo-controlled trials reveal that supplements including copper improved bone mineral density in women (2). Rats deficient in copper have high homocysteine; copper supplementation lowers homocysteine in men (3).
Descriptions of ocular lesions and results of treatment in copper deficiency are minimal (5). It is not clear whether neurological stabilization without cure is from insufficient supplementation or from severe and irreversible deficiency; nerves grow slowly and re-myelination also may be slow (5).
Copper deficiency explains more abnormalities of the patient than other possible, concomitant deficiencies. Their description of the retinal abnormalities may be the most extensive yet published; his visual stabilization is similar to other cases. There is no well-defined regimen of copper replacement therapy regarding chemical form, dose, duration or route of administration. Four mg of oral copper daily (as gluconate) may be effective over some months.
1. Harrison R, Warburton V, Lux A, Atan D. Blindness Caused by a Junk Food Diet. Ann Intern Med. 2019.
2. Klevay LM. Copper. In: Coates PM, Betz, J.M., Blackman,M.R., Cragg, G.M., Levine,M., Moss, J., White, J.D., ed. Encyclopedia of Dietary Supplements. 2 ed. London: Informa Healthcare; 2010:175-84.
3. Klevay LM. Ischaemic heart disease from copper deficiency: a unified theory. Nutr Res Rev. 2016;29:172-9.
4. Klevay LM. Copper deficiency and neuropathology related to the petrous bone. Ann Epidemiol. 2014;24:488-9.
5. Klevay LM. Ocular lesions from copper deficiency. Indian J Med Res. 2017;146:430-1.
Response
Total homocysteine (Hcy) and methylmalonic acid (MMA) levels were measured to understand the significance of our patient’s low-normal vitamin B12 level and clinical history of poor diet; both were mildly elevated. In a targeted strategy to investigate causes of homocystinuria, we use Hcy level as a guide to the likely cause1. Inherited metabolic disorders (IMDs) are rare, generally present in early infancy or childhood and are normally associated with Hcy levels >100µmol/L1. The Hcy level in our case was <50µmol/L at presentation, and the most common causes are delayed sample separation (<1mol/L/hour); hypothyroidism; low-normal or deficient levels of vitamin B6 (pyridoxine), B9 (folate) and B12 (cobalamin); renal impairment; and certain medications1. Hcy levels 50-100µmol/L may occur from the same aetiologies but can be investigated further with plasma amino acids and urine organic acids if the clinical history is suggestive of an IMD.
While it’s true that some IMDs, e.g. remethylation or cobalamin (Cbl) pathway mutations, can be associated with Hcy levels <100µmol/L, the authors cite examples with very different phenotypes2-4. Transcobalamin II (TCII) deficiency presents before age 2 with failure to thrive or haematological abnormalities, e.g. pancytopenia, and those with visual abnormalities have retinopathy, not optic neuropathy3. Disorders of intracellular B12 processing can present in adolescence and adults (CblC and CblD, not CblF or CblJ), but the phenotype is again different2,4. One case of late-onset CblC deficiency had hypertensive retinopathy from malignant hypertension, whereas early-onset cases of CblC deficiency have pigmentary retinopathy, not optic neuropathy4. Likewise, CblF and CblJ deficiencies present in early infancy or childhood, and one case with CblJ deficiency presenting as a neonate had retinal dystrophy, not optic neuropathy2.
IMDs, including disorders of the Cbl pathway, were considered in our patient in light of the elevated Hcy and MMA results. However, the levels of Hcy and MMA in conjunction with the clinical history and response to vitamin supplementation made an IMD unlikely. We do not believe that our patient’s visual loss was due to vitamin B12 deficiency alone, but from the combined deficiencies of multiple nutrients, specifically copper and the B vitamin group, many of which have close inter-relationships in the remethylation and folate cycles of the CNS5. While an IMD would not explain our patient’s low vitamin D, bone mineral density, copper and selenium levels, his poor diet provides an explanation for all of his abnormalities.
References
1. Refsum H, Smith AD, Ueland PM, et al. Facts and recommendations about total homocysteine determinations: an expert opinion. Clin Chem 2004;50:3-32.
2. Sloan JL, Carrillo N, Adams D, Venditti CP. Disorders of Intracellular Cobalamin Metabolism. In: Adam MP, Ardinger HH, Pagon RA, et al., eds. GeneReviews((R)). Seattle (WA)1993.
3. Trakadis YJ, Alfares A, Bodamer OA, et al. Update on transcobalamin deficiency: clinical presentation, treatment and outcome. J Inherit Metab Dis 2014;37:461-73.
4. Huemer M, Scholl-Burgi S, Hadaya K, et al. Three new cases of late-onset cblC defect and review of the literature illustrating when to consider inborn errors of metabolism beyond infancy. Orphanet J Rare Dis 2014;9:161.
5. Sechi G, Sechi E, Fois C, Kumar N. Advances in clinical determinants and neurological manifestations of B vitamin deficiency in adults. Nutrition reviews 2016;74:281-300.
Comment
We would like to caution the authors regarding their diagnosis of nutritional optic neuropathy. They make this diagnosis given elevated levels of homocysteine (Hcy) and methylmalonic acid (MMA) in the context of a history of a vitamin B12 (cobalamin) level in the lower range of normal. While metabolism of both Hcy and MMA are B12 dependent, and elevations can indicate deficiency, these values should normalize following B12 supplementation.1 There are other aetiologies to explain the patient’s biochemical and clinical phenotype that were not explored by the authors.
Both MMA and Hcy are elevated in many inborn errors of cobalamin metabolism.2 In particular, the authors should exclude a diagnosis of transcobalamin II (TCII) deficiency, caused by mutations in the TCN2 gene. It is characterized by elevated MMA and Hcy, and a low or normal B12 level. Although normally detected in infancy, late presentations have been described. Furthermore, partially treated patients can have normal neurological function but present with visual abnormalities including retinopathy.3 Symptoms are progressive, but treatment with intramuscular hydroxycobalamin would represent optimal therapy.
Consideration should also be given to disorders of intracellular B12 processing, such as cobalamin C, D, F and J deficiencies (caused by mutations in MMACHC, MMADHC, LMBRD1, and ABCD4 respectively). These disorders can present across the lifespan with variable symptoms including megaloblastic anemia and optic neuropathy.4 Late presentation with a range of symptoms as well as asymptomatic patients have been described.5 Biochemically, these disorders also present with low or normal levels of B12 in conjunction with elevated total Hcy and MMA. Most importantly, all of these disorders are progressive but treatable. Optimum therapy includes intramuscular hydroxycobalamin with oral folic acid and betaine. Cobalamin X deficiency, due to mutations in HCFC1, ZNF143 and THAP11, can present with similar biochemical findings but is clinically less likely in this case as more severe neurological issues have been reported in the rare number of cases to date.4
On the basis of the information presented we suggest that the patient have further work-up to exclude inborn errors of metabolism. Specifically, we would recommend molecular genetic testing of the genes mentioned above, and/or enzymatic studies if required. Identification of such a disease would inform the patient’s treatment whereas exclusion of these diseases would support the authors’ hypothesis that his optic neuropathy is truly nutritional.
1. Stabler SP. Clinical practice. Vitamin B12 deficiency. N Engl J Med. 2013; 368:149-60.
2. Watkins D, Rosenblatt DS. Inborn errors of cobalamin absorption and metabolism. Am J Med Genet Part C Semin Med Genet. 2011; 157:33–44.
3. Trakadis YJ, Alfares A, Bodamer OA et al. Update on transcobalamin deficiency: clinical presentation, treatment and outcome. J Inherit Metab Dis. 2014;37(3):461-73.
4. Sloan JL, Carrillo N, Adams D, et al. Disorders of Intracellular Cobalamin Metabolism. 2008 Feb 25 [Updated 2018 Sep 6]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews. [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1328/
5. M. Huemer, S. Scholl-Bürgi, K. Hadaya, et al. Three new cases of late-onset cblC defect and review of the literature illustrating when to consider inborn errors of metabolism beyond infancy. Orphanet J. Rare Dis. 2014;9:161.
Junk food is not cheap