Multisystem Processes and Disorders 1 out of 400
An 18-month-old boy is brought to the physician by his mother because of concern that he has not yet begun to walk. He was born at term and exclusively breastfed until 15 months of age. His mother says he has been well, apart from an episode of high fever and seizure 4 months ago for which she did not seek medical attention. He has an older brother who is currently receiving medical treatment for failure to thrive. His parents have no history of serious illness; they are of normal height. His last vaccine was at the age of 4 months. He has never received any supplements or medications. He is at the 20th percentile for length, 10th percentile for weight, and 50th percentile for head circumference. Physical examination shows dry mucous membranes, erosion of the enamel on the lingual surface of the incisors, and carious molars. He has frontal bossing. His wrists are widened, and his legs seem bent. Palpation of the chest shows nodular deformities at the costochondral junctions. Which of the following is the most likely underlying cause of this patient's delay in walking?
Deficiency of cofactor for prolyl and lysyl hydroxylaseThe cofactor for prolyl and lysyl hydroxylase is ascorbic acid (vitamin C). Vitamin C deficiency causes scurvy, which classically manifests with weakness and fatigue (early), followed by mucosal bleeding, curly hair, poor wound healing, and increased susceptibility to severe infection (late). This patient's presentation is inconsistent with scurvy. Multiple bone fractures in different stages of healingMultiple fractures at different stages of healing should raise concern for child abuse. In preambulatory children, specific fractures (e.g., of the ribs, scapula, hands/fingers, and spiral fractures of the femur), are especially concerning. Although this patient has various joint, craniofacial, chest wall, and dental anomalies, his presentation is more concerning for neglect (as suggested by dry mucous membranes, lack of vaccinations, late weaning) rather than child abuse. Mutation of fibroblast growth factor receptor 3Mutations in the fibroblast growth factor receptor 3 gene cause achondroplasia, which manifests with short stature and frontal prominence. However, height is usually below the 5th percentile in achondroplasia. Moreover, this condition is not associated with dental changes or beading of the ribs. Instead, skeletal abnormalities such as microcephaly, short extremities, and scoliosis are typically seen in achondroplasia. Deficiency of osteoclasts to reabsorb boneDeficient osteoclast-mediated bone resorption is the pathophysiologic mechanism of osteopetrosis. This condition is extremely rare in the pediatric population. Most often, these patients present with cranial nerve palsies (from cranial foramen narrowing), hip abnormalities, and an increased tendency for long bone fractures. This patient does exhibit long bone and joint abnormalities, but he lacks fractures or cranial nerve palsies. In addition, osteopetrosis does not result in dental and craniofacial abnormalities or beading of the ribs. Defective growth plate mineralization
Defective growth plate mineralization due to vitamin D deficiency is the cause of rickets. The impaired bone mineralization leads to bead-like costochondral junctions (“rachitic rosary”), erosion of tooth enamel, bone pain and weakening (frontal bossing), abnormal bowing (genu varum), and distention of the bone (widened joints). These bone deformities are responsible for the delay in this patient's walking. Dietary changes (increased vitamin D, calcium, and phosphate intake) and adequate sun exposure are the first-line treatments for rickets.
This patient's malnutrition seems to arise from domestic neglect as suggested by the elder sibling's failure to thrive, the lack of medical attention after a seizure, the lack of vaccinations, and improper feeding practices (i.e., late introduction of solid foods, lack of vitamin D supplementation during first year of life). Defect in type I collagen
Type I collagen defects cause osteogenesis imperfecta (OI), which manifests with very fragile bones that are prone to fracture from minimal trauma. Other classic findings include blue sclerae, poor hearing, and dental abnormalities. While this patient has skeletal abnormalities, he has no history of recurrent fractures or blue sclerae. Moreover, OI does not cause joint abnormalities.
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