Small-for-age toddler is unable to walk

January 1, 2017

A 22-month-old African American boy born at 38 weeks by normal vaginal delivery presents to a local hospital from a private pediatric office for failure to thrive. He was seen by his pediatrician until aged 1 month but was lost to follow-up. His delay in walking prompted his mother to reestablish care at age 22 months.


A 22-month-old African American boy born at 38 weeks by normal vaginal delivery presents to a local hospital from a private pediatric office for failure to thrive. He was seen by his pediatrician until aged 1 month but was lost to follow-up. His delay in walking prompted his mother to reestablish care at age 22 months. 

History of illness

There were no reported complications during pregnancy or delivery. According to his mother, the toddler has always been small and has had slow growth, but he has never lost weight. He was exclusively breastfed until aged 18 months, and his current diet consists of 1 cup of whole milk and several cups of fruit juice per day, grains, meats, and minimal fruits and vegetables. He lives with his mother and 3-year-old sister in public housing. His mother has a history of iron deficiency anemia and sickle cell trait. His maternal grandmother has lupus and rheumatoid arthritis. His sister is reportedly healthy and has appropriate growth and development.

Physical exam

On admission, the patient is notably small for his age and is below the first percentile for weight, height, and head circumference. He is alert and cooperative, and is babbling during the exam. His anterior fontanelle is open and his oropharynx and dentition are normal. No abnormalities are discovered during a cardiopulmonary exam. There are nodules along his rib cage. His abdominal exam is normal and reveals no hepatosplenomegaly or masses. He has bowing deformities of both arms and legs, wide wrists, and mild diffuse hypotonia. Based on a physical exam and history of developmental milestones, he has both gross motor and fine motor delay.

Laboratory and imaging tests

The patient’s blood chemistry panel is presented in Table 1. His urinalysis has 1+ protein (reference range, negative) and is otherwise normal.

Recommended: Toddler with blistering acrodermal rash

A radiograph is obtained at presentation (Figure 1). Because of the findings on imaging, further testing is performed with results as follows: 25-hydroxyvitamin D (25[OH]D), 13 ng/mL (reference range, 30-100 ng/mL); phosphorus, 2.99 mg/dL (reference range, 4.37-6.59 mg/dL); magnesium, 3.1 mg/dL (reference range, 1.7-2.3 mg/dL); and parathyroid, 88 pg/mL (reference range, 14-72 pg/mL).  

Differential diagnosis

The diagnostic considerations of a toddler with failure to thrive are vast (Table 2),1,2 but these can be organized into 1 of 3 categories: inadequate intake, malabsorption, or increased metabolic demand.1 In developing countries, infectious diseases and inadequate nutrition are typically seen as causes for failure to thrive, while in developed countries, causes typically are preterm birth and family dysfunction.2 Inadequate intake is a possible cause for failure to thrive in this patient as there is significant risk for food insecurity and lack of education regarding dietary needs.

This patient has no evidence of oromotor dysfunction or history of emesis that would suggest these as causes of inadequate intake. There is no history of diarrhea, bloody or fatty stools, or other systemic findings to suggest cystic fibrosis, celiac disease, food protein insensitivity, or other processes causing malabsorption. Causes of increased metabolic demand include congenital infections (ie, human immunodeficiency virus [HIV]), chronic renal disease, renal tubular acidosis, cardiac disease, and vitamin deficiencies.1 A detailed patient history and review of systems do not suggest any underlying cardiac or kidney disease, but concerns for vitamin deficiency arise.

Recommended: In utero vitamin D exposure reduces childhood allergic rhinitis risk

For most patients with failure to thrive, there is evidence of an etiology found in the patient’s history and physical exam. For 18 months, this patient was solely breastfed without any vitamin D supplementation, and when he transitioned to cow’s milk, the amount he received did not meet daily vitamin D requirements. This, along with the physical exam and radiographic findings of muscular weakness, fractures, rachitic rosary, enlargement of wrists and ankles, and anterior bowing of long bones are consistent with vitamin D-deficient rickets.


The 2 main sources of vitamin D are sunlight and diet. Both sources begin as cholecalciferol (D3), which then requires 2 separate steps to become the active form, 1,25 dihydroxycholecalciferol, or calcitriol. Hydroxylation occurs in the liver followed by the kidneys where the final step to create the active form occurs. Regulation by parathyroid hormone and serum calcium levels plays a role in activation of calcitriol. Once activated, 1,25 dihydroxycholecalciferol can now bind to the vitamin D receptor. The calcium-binding protein is formed promoting calcium absorption from the gut, which allows for bone mineralization.3,4,5 The American Academy of Pediatrics (AAP) recommends exclusive breastfeeding for the first 6 months of life and supplementation with 400 IU daily of vitamin D. The recommendation for children aged 1 to 18 years is 600 IU per day. Therefore, if transitioning to cow’s milk around 1 year of age, children should receive 2 to 3 servings of milk per day (16-24 oz/d) to meet this requirement.

Rickets is a result of poor bone mineralization. Without vitamin D, calcium and phosphorous are poorly absorbed, leading to insufficient mineralization.6 These hormonal regulatory factors promote hypertrophic growth plate apoptosis, which allows for the replacement of matrix and eventually leads to bone generation. The hypertrophic chondrocytes are not resorbed because of defective apoptosis and the irregularly calcified growth plate expands.7 This expansion of hypertrophic cells gives rise to the clinical features of rickets: hypertrophy and widening of costochondral junctions, wrists, and knees, and poor mineralization leading to bowed weight-bearing limbs and delayed growth.8,9

The radiologic images of the patient highlight these findings (Figures 2 and 3).

Typical presentation of rickets

Although vitamin D deficiency is likely on the rise in the United States, most children with this deficiency do not present with rickets as highlighted in this case, and especially not to this severity. However, understanding the typical presentation helps to identify and treat the disease at an earlier point. Multiple retrospective analyses have shown that the clinical presentation will vary depending on the age of presentation, which is likely related to the skeletal development and motor development in childhood because rickets is typically seen during periods of peak growth.5

A study performed in Spain by Yeste and colleagues10 found that nearly 50% of children with rickets aged from 6 to 12 months present with failure to thrive, and 69% of children aged 12 months and older present with growth failure, seizures, fractures, and laboratory evidence of rickets. Only about 29% of the infants aged 6 to 12 months in the study showed external signs or bony deformities.

A retrospective analysis from Torun and colleagues11 also divided subjects into age groups to assess for patterns of symptoms at diagnosis. Children aged from 1 to 3 years present with muscular weakness (91%), failure to thrive (89%), and bony deformities (29%).

DeLucia and associates12 assessed the clinical presentation and severity of growth delay by comparing growth parameters. The majority of subjects presented after 12 months of age and were breastfed for an average of 12.5 months. Only 20% received appropriate vitamin D supplementation. Skeletal abnormalities and failure to thrive were the 2 most common clinical presentations. Growth parameters of these children were striking, with 65% below the 5th percentile for height and 43% below the 5th percentile for weight.12 Extraskeletal findings of patients with rickets include “hypocalcemia lead[ing] to tetany, seizures, laryngospasm, and hypocalcemic cardiomyopathy and death.”6 Other findings include irritability and delayed motor milestones. Based on these data, the skeletal findings characteristic of rickets are unlikely to be the presenting complaint. Therefore, recognizing vitamin D deficiency as a cause of failure to thrive may prevent severe cases in at-risk populations.

Risk factors

Because melanin acts as a barrier to vitamin D synthesis, nutritional rickets is more likely to be found among members of certain racial or ethnic groups with darker skin complexion, such as African Americans, Hispanics, and Middle Easterners.10,12-14 Rickets is also more common among infants who are solely breastfed without adequate supplementation or who are poorly transitioned from cow's milk. It has been shown that breastfed infants of mothers with adequate vitamin D stores will be vitamin D deficient within 8 weeks.5

Rickets is also more likely to develop during winter months at higher altitudes because there is “an increase in the sun’s zenith angle [that] results in an increased path length for the [ultraviolet]B photons to travel,” therefore, little-to-no vitamin D is produced.5,6 Many of these risk factors likely contribute to the nutritional rickets seen in this patient. Recognizing the clinical and laboratory patterns of nutritional rickets remains essential in the diagnostic process. Acknowledging patients’ risk factors might also serve as a preventive measure to avoid the severity seen in this case.

In general, for children aged from 1 to 18 years who are vitamin D deficient, the Endocrine Society recommends 2000 IU daily of vitamin D2 or D3, or 50,000 IU of vitamin D2 or D3 weekly for at least 6 weeks with a goal serum 25(OH)D level greater than 30.15 It has been shown that in a short-term period with rachitic patients, similar increases in 25(OH)D levels are seen with either D2 or D3. Because it is possible that D2 is metabolized more quickly than D3, many clinicians use D3 for therapy.16 Depending on age, maintenance therapy is 400 IU/d to 1000 IU/d for children aged 0 to 1 year and 600 IU/d to 1000 IU/d for those aged 1 to 18 years.

Follow-up radiologic imaging can be a helpful determinant of recovery. The first sign of recovery is the “healing line of rickets, which is a radio-opaque line in the epiphysis signifying that mineralization of the provisional zone of calcification has begun.”17 Neuromuscular findings, including hypotonia that can lead to motor delays such as those seen in this patient, are well described as features of rickets and are shown to occasionally be reversible with vitamin D repletion and supplementation.18 Given the significant motor delay in this patient, ensuring adequate follow-up and referrals for therapies are other key components in treatment of nutritional rickets.

Patient outcome

The patient is promptly treated with a 1-time dose of 50,000 IU of D3 during admission followed by 2000 IU of D3 daily until healing is noted on follow-up imaging. He is also given calcium supplementation to avoid hypocalcemia that occurs with rapid remineralization of the bony matrix. The remainder of admission involves a strict calorie count, close monitoring of weight gain, lab surveillance, dietary education, and coordination with social work to ensure the safety of the child and coordination for follow-up.

Next: What disease processes may mimic child abuse?

During follow-up 4 weeks later, imaging shows healing rickets (Figure 4). The patient is transitioned to 800 IU daily with plans to follow every month with serial exams and radiologic imaging.


Nutritional rickets, although seemingly rare, continues to be reported within the United States. When seeing patients with growth failure, especially infants and toddlers, one should obtain a detailed dietary history and consider vitamin D deficiency as a possible cause. Most children with failure to thrive do not have an underlying medical cause. However, those that do, such as the patient in this case, will usually have physical exam findings that hint toward a diagnosis. Prompt diagnosis and treatment of patients at risk for nutritional rickets will improve developmental outcomes.



1.    Jaffe AC. Failure to thrive: current clinical concepts, Pediatr Rev. 2011;32(3):100-107.

2.    McLean HS, Price DT. Failure to thrive. In: Kleigman RM, Stanton BF, St. Geme JW III, Schor NF, Behrman RE, eds. Nelson Textbook of Pediatrics. 19th ed. Philadelphia, PA: Elsevier Saunders; 2011:147-149.

3.    Pettifor JM. Vitamin D deficiency and nutritional rickets in children. In: Feldman D, Pike WJ, Adams JS. Vitamin D. 3rd ed. London: Academic Press/Elsevier; 2011:1107-1128.

4.    St-Arnaud R, Demay MB. Vitamin D biology. In: Glorieux FH, Pettifor JM, Jüppner H. Pediatric Bone: Biology and Diseases. 2nd ed. London: Academic Press/Elsevier; 2012:163-187.

5.    Elder CJ, Bishop NJ. Rickets. Lancet. 2014;383(9929):1665-1676.

6.    Holick MF. Resurrection of vitamin D deficiency and rickets. J Clin Invest. 2006;116(8):2062-2072.

7.    Özkan B. Nutritional rickets. J Clin Res Pediatr Endocrinol. 2010;2(4):137-143.

8.    Tiosano D, Hochberg Z. Hypophosphatemia: the common denominator of all rickets. J Bone Miner Metab. 2009;27(4):392-401.

9.    Mughal MZ. Rickets. Curr Osteoporos Rep. 2011;9(4):291-299.

10. Yeste D, Carrascosa A. Nutritional rickets in childhood: analysis of 62 cases [article in Spanish]. Med Clin (Barc). 2003;121(1): 23-27.

11. Torun E, Genç H, Gönüllü E, Akovali B, Ozgen IT. The clinical and biochemical presentation of vitamin D deficiency and insufficiency in children and adolescents. J Pediatr Endocrinol Metab. 2013;26(5-6):469-475.

12. DeLucia C, Mitnick ME, Carpenter TO. Nutritional rickets with normal circulating 25-hydroxyvitamin D: a call for reexamining the role of dietary calcium intake in North American infants. J Clin Endocrinol Metab. 2003;88(8):3539-3545.

13. Weisberg P, Scanlon KS, Li R, Cogswell ME. Nutritional rickets among children in the United States: review of cases reported between 1986 and 2003. Am J Clin Nutr. 2004;80(6 suppl):1697S-1705S.

14. Michel H, Olabopo F, Wang L, Nucci A, Greenspan SL, Rajakumar K. Determinants of 25-hydroxyvitamin D concentrations in infants and toddlers. Curr Nutr Food Sci. 2015;11(2):124-130.

15. Holick, MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911-1930. Erratum in: J Clin Endocrinol Metab. 2011;96(12):3908.

16. Thacher TD, Fischer PR, Tebben PJ, et al. Increasing incidence of nutritional rickets: a population-based study in Olmsted County, Minnesota. Mayo Clin Proc. 2013;88(2):176-183.

17. Chatterjee D, Gupta V, Sharma V. Sinha B, Samanta S. A reliable and cost effective approach for radiographic monitoring in nutritional rickets. Br J Radiol. 2014;87(1036):20130648.

18. Fluss J, Kern I, de Coulon G, Gonzalez E, Chehade H. Vitamin D deficiency: a forgotten treatable cause of motor delay and proximal myopathy. Brain Dev. 2014;36(1):84-87. 

Dr Lindley is a third-year pediatric resident, Saint Louis University School of Medicine, SSM Health Cardinal Glennon Children’s Hospital, Saint Louis, Missouri. Dr Farmakis is medical director of Pediatric Radiology and assistant professor of Radiology, Department of Radiology, Saint Louis University School of Medicine, SSM Health Cardinal Glennon Children’s Hospital, Saint Louis. Dr Tanios is assistant professor, Department of Pediatrics, Saint Louis University School of Medicine, SSM Health Cardinal Glennon Children’s Hospital, Saint Louis. The authors have nothing to disclose in regard to affiliations with or financial interests in any organizations that may have an interest in any part of this article.