Symptomatic Vitamin C Deficiency in Two Developmentally Delayed Toddlers

AUTHORS:
Katie Reisman Lynch, PA-C • Rafael Santiago, MD

AFFILIATION:
Lakeland Regional Medical Center, Lakeland, Florida

CITATION:
Lynch KR, Santiago R. Symptomatic vitamin C deficiency in two developmentally delayed toddlers. Consultant. 2020;60(7):e4. doi:10.25270/con.2020.05.00010

Received January 4, 2020. Accepted April 21, 2020.

DISCLOSURES:
The authors report no relevant financial relationships.

CORRESPONDENCE:
Katie Reisman Lynch, PA-C, Department of Pediatric Emergency Medicine, Lakeland Regional Medical Center, 1324 Lakeland Hills Blvd, Lakeland, FL 33804 (katieellenreisman@gmail.com)

The two case reports presented here explore entirely different presentations of the same diagnosis, scurvy, in two children with autism spectrum disorder (ASD). Case 1 is a 3-year-old boy with leg pain, unexplained bruising, and a limp. Case 2 is a 4-year-old boy with a raw, nonhealing rash on the diaper area. Thorough workup revealed both patients to have severe vitamin C deficiency consistent with scurvy. Although scurvy is rarely seen in developed countries, it should continue to be considered, especially in children with poor nutritional intake and unexplained symptoms. These cases highlight the need for thorough evaluation of pediatric limp and nonhealing rashes, including a complete history, physical examination, imaging studies, and laboratory assessment.

CASE 1

A fully vaccinated 3-year-old boy with a history of constipation and unspecified developmental delay presented to the emergency department (ED). His parents reported that the boy had been “favoring one leg one day and the other leg the next day.” The parents also stated that he had been having intermittent leg pain for approximately 3 months, occasionally accompanied by a limp. The parents reported that the limp does not always favor the same leg. Additionally, the parents noted that the boy persistently has bruises on his lower legs despite having no history of known injury or trauma.

On initial evaluation, the patient was nonverbal. Evidence of contusions was present on the anterior tibias bilaterally, with mild overlying tenderness. The skin was intact. All extremities had normal range of motion and normal strength and were without obvious swelling or deformity. He ambulated with a stiff-legged gait.

Plain radiographs of the left lower leg, left femur, and left hip with pelvis were all unremarkable. Without evidence of an acute emergent process, the patient was discharged home with a prescription for ibuprofen, and the parent were instructed to follow up with his pediatrician in 2 to 3 days.

Four days later, the boy was brought back to the ED with a chief concern of leg pain. A history obtained at this visit revealed that the patient had had bilateral lower leg bruising and “lumps” for a few days, with difficulty walking for the past 1 to 3 months. The parents stated that the boy had been unable to run for approximately 1 month. The boy had not yet had a follow-up visit to his pediatrician after his recent ED visit.

During this second ED visit, the patient was able to kick his legs with equal strength. Multiple areas of bruising were present along the anterior shins bilaterally, with palpable lumps under the areas of ecchymosis (Figure 1). Palpation over the anterior shins did not elicit any apparent discomfort. The patient had a stiff gait bilaterally but walked without hesitation.

The results of a complete blood cell count were unremarkable except for a hemoglobin level of 8.7 g/dL (reference range, 10.9-15.0 g/dL). Prothrombin time, partial thromboplastin time, and international normalized ratio were within normal limits. Electrolyte levels were unremarkable except for a carbon dioxide level of 19 mEq/L (reference range, 23-29 mEq/L). The creatinine kinase (CK) level was within normal limits. The C-reactive protein (CRP) value was negative. Results of a hepatic function panel were significant for a minimally elevated aspartate transaminase (AST) level of 45 U/L (reference range, 10-40 U/L). A vitamin C level was obtained and sent out to a laboratory.

Because the laboratory test results did not indicate any specific diagnosis, but the patient continued to have unexplained symptoms, he was transferred to a pediatric tertiary care center for further evaluation. At the tertiary care center, the patient’s workup findings were again nonspecific. He had improvement of his walking the following day and was discharged with recommended outpatient follow up to his pediatrician.

Eight days later, the patient returned to our ED for evaluation of ongoing leg pain. While at the tertiary care center, the boy had been diagnosed with ASD and developmental delay. No other diagnoses had been made. At this third ED visit, the parents stated that the boy had had pain when getting out of his highchair. Again, laboratory assessment was obtained. Significant findings included a hemoglobin level of 8.0 g/dL (reference range, 10.9-15.0 g/dL) and an AST level of 46 U/L (reference range, 10-40 U/L). Electrolyte levels, erythrocyte sedimentation rate, CRP level, and CK level were all within normal limits.

Review of the patient’s medical record revealed that the results of the vitamin C level test taken at the second ED visit had returned with a value less than 0.1 mg/dL (reference range, 0.2-2.0 mg/dL). An attempt had been made to contact the patient’s family regarding this abnormal result, but the patient’s recorded contact information had been invalid. A letter had been sent to his primary care provider, but the information had not yet been relayed to the family. Given that vitamin C levels of less than 0.3 mg/dL indicate significant deficiency, the patient was diagnosed with vitamin C deficiency (scurvy). A 50-mg dose of ascorbic acid (vitamin C) was administered in the ED. The patient was admitted to the pediatric service for further management.

Retrospective chart review later revealed a thorough dietary history. The parents had described the boy as a very picky eater, stating that he will drink only chocolate milk or water and that he refuses all fruit juices. They occasionally had given him watered-down orange soda. They reported that the boy occasionally will eat grapes but refuses to eat any vegetables. The parents reported only giving him the foods that they know he will eat.

CASE 2

A 4-year-old boy with history of ASD was brought to the ED with concern for “raw sores” in the diaper area. The parents stated that the boy had been evaluated by multiple physicians, and that they have tried treating the rash with triamcinolone, mupirocin, and an over-the-counter menthol and zinc containing diaper barrier cream. They report that the symptoms had waxed and waned over the past several months, and that the rash worsened with increased bowel movements. The boy had no allergies and was up-to-date on vaccinations. He had had no recent fever, chills, nausea, vomiting, or changes to dietary habits. The parents stated that the boy will eat only yogurt, oatmeal, and pudding.

Physical examination findings were significant for a warm, dry, rash on the perirectal region with redness and denuded skin (Figure 2). No obvious petechiae or purpura were present, and there was no active drainage.

The differential diagnosis included Candida diaper rash, zinc deficiency with acrodermatitis enteropathica, and vitamin C deficiency. The patient was discharged home with laboratory test results for zinc and vitamin C levels pending. Discharge instructions encouraged the parents to increase the boy’s daily zinc consumption and follow up with a dermatologist. He was given a refill of mupirocin ointment, and the parents were encouraged to use a basic diaper cream in lieu of a menthol-containing barrier cream. They were advised to discontinue the triamcinolone cream.

Laboratory tests revealed a vitamin C level of less than 0.01 mg/dL (reference range, 0.6-2.0 mg/dL). The family was contacted and informed of the results. Vitamin C supplementation was initiated. During a follow-up phone call, the patient’s mother stated that the boy’s rash had resolved entirely within 4 weeks of initiation of vitamin C supplementation.

DISCUSSION

Vitamin C has many enzymatic and nonenzymatic actions in the human body that are imperative to normal physiologic function. Vitamin C is enzymatically involved in collagen hydroxylation, tyrosine metabolism, biosynthesis of norepinephrine, and amidation of peptide hormones. Nonenzymatically, it protects low-density lipoproteins from oxidation, reduces harmful oxidants in the stomach, and helps promote iron absorption.¹

In 1989, the Food and Drug Administration (FDA) published a recommended dietary allowance (RDA) of 60 mg/day of vitamin C. In 1999, researchers reevaluated these recommendations based on 9 criteria²: dietary availability; steady-state concentrations in plasma in relationship to dose; steady-state concentrations in tissues in relationship to dose; bioavailability; urine excretion; adverse effects; biochemical and molecular function in relationship to vitamin concentration; direct beneficial effects and epidemiologic observations in relationship to dose; and prevention of deficiency. The researchers evaluated the estimated average requirement and proposed that the RDA should be increased to 120 mg/day. Their calculations also suggested that an intake of greater than 1000 mg/day would lead to adverse effects.² Today, the National Institutes of Health, based on recommendations developed by the Food and Nutrition Board of the National Academy of Sciences, suggests an RDA of 90 mg/day for adult men and 75 mg for adult (nonpregnant, nonlactating) women.³

Vitamin C, one of only four dietary antioxidants, is a necessary cofactor in collagen biosynthesis.^4,5 Humans, unlike other animals, cannot convert glucose into vitamin C. Therefore, inadequate dietary intake of vitamin C can lead to deficiency and therefore depletion of pericapillary collagen.⁶

Initial signs of scurvy include weakness and irritability; vague, dull aching pains in the muscles or joints of the legs and feet; and weight loss. As the disease progresses, signs and symptoms may present in the skin, mouth, eyes, blood, and bones. These findings can include follicular hyperkeratosis, diffuse petechial hemorrhages, swollen joints, gingival bleeding, peripheral edema, irregular masses of calcified cartilage, and decreased density of bone shafts. These signs and symptoms may also be accompanied by some level of anemia. In children, the most frequent symptoms are general irritability, tenderness of the limbs (especially the legs), pseudoparalysis, anemia, and gingival bleeding.⁷

In 2004, a study that reviewed the Third National Health and Nutrition Examination Survey (1988–1994) revealed that vitamin C deficiencies are more common in the United States than had been thought.⁸ The authors of the study concluded that males, cigarette smokers, and non-Hispanic black males are most likely to be vitamin C–deficient. The 12- to 17-year-old age group and the 65 and older age group were least likely to be vitamin C–deficient. The authors attributed this to the prevalence of vitamin supplementation in these age groups.⁸

A number of studies have reviewed the incidence of ASD and food selectivity. A 2013 study specifically looked into ASD, food selectivity, and subsequent nutritional inadequacy.⁹ This study revealed that few previous studies had assessed the nutritional adequacy of diets of children with ASD. These previous studies had mixed findings. One study found no difference in the adequacy of the nutrient intakes in children with ASD compared with typically developing children.¹⁰ Another study found inadequate nutrient intake in children with autism compared with neurotypical children—specifically, an inverse relationship between variety and nutritional adequacy was found.¹¹

SUMMARY

Although scurvy is thought of as a disease of the past, it is still prevalent in the United States. It should remain in the differential diagnosis not only for patients who present with hemorrhagic symptoms, but also for patients who present with nonspecific limb pain or poor wound healing and rash. In patients with ASD, a thorough nutritional history may suggest uncommon nutritional deficiencies.

Food selectivity is very common among children and even adults with ASD. These patients and their caregivers should be educated thoroughly about the risks of nutritional deficiencies and proper supplementation.

In case 1 above, a patient with ASD presented to the ED secondary to leg pain and pretibial contusions. Case 2 involved a patient with ASD and a nonhealing rash. Laboratory analysis in both patients’ cases revealed significant vitamin C deficiency. Both patients’ food selectivity precluded them to vitamin C deficiency. These cases emphasize the need to perform a thorough nutritional history, particularly in patients with ASD.

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