Children with developmental disabilities are at risk for malnutrition as a result of oropharyngeal dysphagia, interactions between nutrients and medications, altered energy and nutrient requirements, and their reliance on others to feed them. Several studies have documented alterations in weight and height parameters in these children (1). Recently, technologic advances such as percutaneous gastrostomy tube placement have significantly improved the nutritional status of many of these patients. In addition, a variety of proprietary formulas are being increasingly used to provide these patients with nutritional support. We describe a patient with developmental delay who received an elemental formula through a gastrostomy tube and who, despite normal energy balance and macronutrient status, developed signs and symptoms consistent with scurvy. He had severe vitamin C deficiency and deficiencies of vitamin A and zinc.
The patient was a 3-year-old boy with a history of cerebral palsy, developmental delay, and seizure disorder as a result of birth asphyxia. He had a 1-month history of irritability, bleeding gums, low-grade fever, and rash. He had been diagnosed with a fracture of the left femoral metaphysis 6 weeks before admission and had increasing irritability despite treatment with methadone. Twenty months before admission, esophagogastroduodenoscopy was performed for symptoms of recurrent vomiting and revealed an eosinophilic infiltrate of the antrum and esophagus. An amino acid–based formula (Neocate One+, SHS North America, Gaithersburg, MD, USA) was therefore started at 800 mL/d. Despite using this formula and using prokinetic agents, the vomiting persisted, so he underwent Nissen fundoplication and gastrostomy tube placement 8 months before admission. He previously had been prescribed a multivitamin supplement, but this was discontinued 10 months before admission because of concern over persistent vomiting. Medications at admission included phenobarbital, diazepam, baclofen, and methadone.
At physical examination, his weight was at the 50th percentile for age. He was a nonverbal child who responded to his mother. He had microcephaly and gingival hypertrophy, with violaceous, friable mucosa and gum bleeding (Fig. 1). Results of chest and cardiac examinations were normal. His abdomen showed the presence of a gastrostomy tube, around which was a small area of ecchymoses and some dried blood. His skin showed a perifollicular, petechial rash on his upper extremities, lower extremities, back, and trunk (Fig. 2). There was a moderate amount of pitting edema to the mid shin of the lower extremities.
Laboratory results at admission were notable for a white blood cell count of 8.53 × 10 3 , with a normal differential, a hematocrit concentration of 34.9%, and a platelet count of 335 × 10 3 . His electrolyte levels were normal and serum albumin concentration was 2.4 mg/dL. His prothrombin time was 12.6 seconds, and the partial thromboplastin time was 30 seconds. Urinalysis revealed 5 to 10 white blood cells per high-powered field, 20 to 50 red blood cells per high-powered field, but no evidence of proteinuria or ketonuria. His stool test result was negative for occult blood. Spot fecal fat and stool α 1 -antitrypsin test results were also normal.
A skeletal survey at admission showed a comminuted fracture of the right humeral head and transverse fractures of the left humeral head, distal femurs, and proximal fibulas. There was also diffuse demineralization and thinning of the cortex (Fig. 3). Because of strong clinical suspicion that the child had scurvy, vitamin C administration (300 mg/d) and a multivitamin supplement was begun. Within 24 hours of this therapy, the patient had significantly less irritability and decreased gum hypertrophy and resolving petechial rash. Peripheral edema also resolved within 48 hours. Review with the mother about the formula preparation revealed correction mixing of water and formula powder. Laboratory values during hospital stay confirmed severe vitamin C deficiency and also indicated that the patient was deficient in vitamin A and zinc (Table 1).
One month after discharge, radiographic studies revealed marked callus formation around an elevated periosteum as a result of periosteal hemorrhages (Fig 4). Blood concentrations of vitamins A and C were normal, and his zinc level was increased, although still below the normal range. Samples from three separate lots of Neocate One+ were sent to an outside laboratory and the mean (SD) concentrations of ascorbic acid and zinc were 18.8 (1.2) mg and 3.8 (0.2) mg/100 g of powder, respectively. These amounts exceed the product label of 12.4 mg ascorbic acid and 3.08 mg zinc/100 g of powder.
The nutritional requirements of patients with developmental delay in general and cerebral palsy in particular are poorly understood. Studies using indirect calorimetry confirm that energy requirements are often much lower than standard predictive equations suggest (2). This has been hypothesized to be a result of decreased energy of activity, decreased muscle tone, or lowered growth potential. As a result, the amount of energy provided in gastrostomy feedings is often reduced to match energy needs, and this can be as low as 50% of the usual age-based recommended dietary allowance (RDA) for energy. Our patient was receiving 800 kcal/d (3,341 kJ/d) or 63 kcal · kg −1 · d −1 (263 kJ · kg −1 · d −1 ), whereas the RDA for a 3-year-old boy is 102 kcal · kg −1 · d −1 (426 kJ · kg −1 · d −1 ). His growth during the several months before admission would suggest that this energy intake was adequate to maintain normal weight for his age.
Most formulas designed for children aged 1 to 10 years meet the RDA for micronutrients when they are given in volumes between 980 mL/d and 1,100 mL/d. Amino acid–based formulas, however, generally have a lower concentration of micronutrients, and therefore more volume must be given to meet the RDA. For children aged 4 to 10 years, this amount can be as high as 1,400 mL/d to 2,000 mL/d. When patients receive less than the RDA for energy, their micronutrient intake may be inadequate. Our patient was receiving 70% or less of the RDA for three micronutrients (Table 2). His history, physical, and laboratory findings were all consistent with frank scurvy. He also had biochemical evidence of vitamin A and zinc deficiencies. Our case is similar to the one that Yuwono et al. (3,4) recently presented in abstract form. The child in their report also had a history of neurodevelopmental delay, gastroesophageal reflux requiring fundoplication, and prolonged feeding with Neocate One+ formula. They reported the blood vitamin C level as 0. They presented no further data concerning other micronutrient concentrations.
The origin of scurvy in our patient was probably attributable to low vitamin C intake because his dietary intake was roughly 62% of the RDA. However, because the RDA for micronutrients is set to meet the nutrient requirements of “nearly all (97–98%) healthy individuals in a group”(5), many individuals ingest less than the RDA and do not have vitamin deficiencies. In adults, the RDA for vitamin C is 60 mg, but it has been estimated that 10 mg is the minimum amount needed to prevent the signs of scurvy (6). Others have suggested that healthy adults require at least 41 mg/d to maintain plasma ascorbic acid levels less tan 0.4 mg/dL (7).
In addition to low dietary intake of vitamin C, our patient's use of phenobarbital may have altered his metabolism of vitamin C (8,9). Phenobarbital and other drugs have been reported to increase hepatic synthesis of ascorbic acid in rats and to induce cytochrome enzymes responsible for ascorbic acid degradation (10). Few studies in humans have been reported on this issue.
Nutritional therapy can be helpful in managing a wide variety of gastrointestinal diseases, including inflammatory bowel disease, cow milk protein and other allergic enteropathies, celiac disease, and short bowel syndrome, and an increasing variety of enteral nutrition products are commercially available to the clinician. The current case underscores the need for vigilance in monitoring nutrient intake in patients who receive special formulas or whose nutrient requirements may be unknown. Even apparently healthy children can have unusual dietary intake patterns (11). Pediatric patients receiving amino acid–based formulas may be at particular risk of nutrient deficiencies, even in the presence of normal weight and positive energy balance, and should undergo careful monitoring of micronutrient status and be administered supplementation when indicated.
The authors thank Dr. Nalton Ferraro, Dr. Robert Cleveland, and Lingtak Chan (Boston Children's Hospital) for their assistance.
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