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Home , Hypervitaminosis, Hypervitaminosis A

Physeal Closure from Chronic A Intoxication Deborah Wenkert 1, William H. McAlister 2, Michael P. Whyte 3. 1Center for Metabolic Bone Disease and Molecular Research, Shriners Hospital for Children, St. Louis, MO, USA, 2Mallinckrodt Institute of Radiology, and, 3Division of Bone & Diseases; Washington University School of Medicine, St. Louis, MO, USA. Abstract: An excess of or its analogues have a number of adverse effects on multiple organ systems including on the Symptoms of Vitamin A (Myhre et al. 2003) skeleton. Premature growth plate fusion from vitamin A and D toxicity was first reported in animal hind limbs (“hyena Constitutional Symptoms Gastrointestinal System Skin and Hair and Vision disease”). Subsequently, in 1962, 3 of 7 children with growth retardation from vitamin A toxicity had early lower limb Loss of appetite Vomiting Alopecia Bulging of fontanel Fever Constipation Desquamation physeal closure (JAMA; 182:980). Further reports concerned vitamin A derivatives used in severe pediatric dermatoses Cerebral irritability Sleep disturbance Cirrhosis Dryness or cancers. Increased CSF pressure Tiredness Abdominal pain Exanthema Photophobia Fatigue Diarrhea Hemorrhage Hydrocephalus A 6-yr-old boy with a history of A, associated with fibrosis, was referred for “epimetaphyseal Nausea Pigmentation change Blurred vision Impaired Immunity Hepatomegaly Pruritus disease”. Birth weight was 10 lbs, and he walked at 10 mo. At that time, gastroenteritis was reportedly treated by a Depression Splenomegaly Lip fissure chiropractor with a dose of 3 million units (U) of vitamin A over 16 days, followed by 60,000 U/d except when intercurrent Musculoskeletal System Dizziness Osteopenia Headache illness prompted ~20 additional 3 million U, 16-day courses. By age 2 ½ yrs, fingernails reportedly “bubbled up and fell Vascular System Urogenital System Hyperostosis Ataxia off”, speech regressed, and gross motor skills were lost. Hospitalization elsewhere revealed a critically ill, anorexic child Edema, head Dysuria or altered urination Skeletal pain Edema, face pattern with shiny, hairless, jaundiced skin, icterus, mouth sores, mucosal bleeding, pseudotumor cerebri, ataxia, and marked Joint pain Menstrual changes Edema, leg or ankle Muscular stiffness hepatosplenomegaly. Laboratory studies revealed a coagulopathy, hepatitis, anemia, and thrombocytopenia, but normal and pain serum Ca, P, and Mg levels. Alkaline phosphatase was elevated at 827 IU/l. was diagnosed. After Growth plate fusion* were stopped, he resumed walking and eating within 9 mo. Nevertheless, leg bowing, noted at age 3, Proliferative enthesopathies worsened. Radiographs at age 5 showed physeal closure within distal femurs and proximal and distal tibias. Periostitis

Upon referral, he had dysphagia, dyspnea, anemia, bleeding tendency, morning stiffness, knee and ankle pain, but took * Not listed by Myhre Our patient had the symptoms in blue. only . Height was 5%, weight 75%, sitting height 50%, arm span 75%, and head circumference >>95%. He had petechia, bruises, telangiectasias, hypertelorism, cupped optic discs, and splenomegaly (17 cm) without hepatomegaly, 2 10/12 years 6 years 30° knee contractures, enlarged warm ankles and knees, and bowed tibias. Radiographs revealed the physeal closure, Sample of currently now with relative overgrowth of fibulae, and 1/2 yr later, closure of the proximal fibular physes. Physes elsewhere SERUM VITAMIN LEVELS 2 9/12 YEARS 6 YEARS Ref Range available Vitamin A Discussion (cont) remained open. Vitamin A () 49 20 20-43 mcg/dl 6 years 6 ½ years 5years supplement. : Alpha-Tocopherol 9.1 8.2 2.9-16.6 mg/l Thus, clinicians should be alert to vitamin supplement use in their patients, The bony manifestations of Long-term follow-up of physeal fusion from vitamin A toxicity (eg. 12 yrs: JBJS[Am] 1974;56:1283) suggests Beta Gamma Tocopherol 0.3 0.5-3.8 mg/l Vitamin C: (Ascorbic Acid) < 0.24 0.2-1.9 mg/dl hypervitaminosis A can range from pain, with or without fractures, to significant skeletal deformity. Osteopenia disproportionate, assymetric shortening of lower limbs. Narrowing of physes from can resolve (Am J Dis Child from vitamin A or retinoic acid derivatives can result from subperiosteal cortical bone loss as shown by CT which : 1,25(OH)2 11.74 15-80 pg/ml 6 years Discussion 1988;142:316-8). Experience with our patient suggests that reversal of physeal fusion is not possible if vitamin A toxicity 25(OH) 26 15-40 ng/ml can be blocked by biphosphonates acting on the . In a 1950 paper regarding vitamin A toxicity, Dr. has been severe and prolonged. Vitamin B12 > 2000 200-1000 pg/ml Caffey commented, “In no case did a manufacturer’s label state the harmful effects of overdosage (which) is a Vitamin K1 13.39 0.1-2.2 ng/ml We have described a 6 1/2-year-old boy with irreversible physeal fusion series of physeal fractures (21), distal femur physes had a disproportionately high incidence of posttraumatic bridge serious error of omission and should be corrected”. BIOCHEMISTRIES 2 9/12 YEARS 6 YEARS Ref Range from vitamin A toxicity. His radiographs at age 5 years were illustrated in formation, accounting for 33% of all premature physeal bridges but only 1.4% of physeal fractures. Also noted, was ESR Sedrate 47 8 0-20 mm/hr Introduction 2007 in a brief report. (2) the earliest physiologic (as well as pathologic) closure site of the distal femoral physis is the central region relating to PT 17.6 17.3 12.1-14.1 seconds retinol INR 1.38 2 the central physeal undulation. Thus, the pattern of involvement in physeal closure in vitamin A toxicity in our patient Skeletal manifestations of hypervitaminosis A in adults include periosteal elevation and thickening, bone pain, Experience with our patient’s abnormal appearance of the growth plates, as References PTT 52.7 37.7 26.5-38.5 seconds O parallels that of other causes of premature physeal closure. hyperostosis, , periarticular calcification, ligament and tendon calcification, DISH, and osteophyte H well as his subsequent physeal fusion, raise a number of issues concerning Biliburin: Total 3 1.5 0.2-1.0 mg/dl Vitamin A and growth plate biology: 1. Nesher G Zuckner J. Rheumatologic complications of vitamin A and . Semin ArthritisRheum. 1995;24:291-296. formation.(1) In children, whose skeletons are growing and undergoing modeling, additional complications can occur. Direct 1.5 - < 0.3 mg/dl 2. Saltzman MD, King EC. Central physeal arrests as a manifestation of hypervitaminosis A. J Pediatr Orthop 2007;27: 351-353. : Total 9.3 8.6 8.8-10.8 mg/dL 3. Toomey J Morissette R. Hypervitaminosis A. Am J Dis Child. 1947;473-480. 4) What is the histopathology of Vitamin A excess in the growth plate? 4. Pickup JD. Hypervitaminosis A. Archives of Disease in Childhood. 1956;31:229-232. Ionized 1.27 mMol/L 4.9 mg/dl Physeal fusion due to vitamin A toxicity is not as well known as the painful periostitis leading to undulating diaphyseal 1.08-1.34 mMol/L isotretinoin 1) Our patient received a number of vitamin supplements. Did 5. Woodard JC Donovan AG Eckhoff C. Vitamin (A and D)-induced premature physeal closure (Hyena Disease) in calves. J Comp Path. 1997;353-366. 4.5-5.3 mg/dL (age 6) Deficiency of vitamin A inhibits longitudinal bone growth (22). The long bones of vitamin A deficient animals are 6. Woodard JC Donovan GA Fisher LW. Pathogenesis of vitamin (A and D)-induced premature growth-plate closure in calves. Bone. 1997;21:171-182. cortical thickening , skin and and increased . Accordingly, here we report a case of Magnesium 2.2 1.7 1.8-2.4 mg/dL vitamin A cause his premature physeal closure? 7. Yamamoto K Sadahito K Yoshikawa M Nobuyuki O Mikami O Yamada M Nakamura K Yasuyuki N. Hyena disease (premature physeal closure) in calves due to shorter and thicker than those of healthy animals, with the shortness being viewed as a failure of endochondral bone overdose of vitamins A, D3, E. Vet Hum Toxicol. 2003;45:85-87. severe vitamin A intoxication in a 6 1/2-year-old boy which led to irreversible lower extremity growth plate fusion. Phosphate 4.6 4.5 4.0-7.0 mg/dL O O The teratogenicity, hepatic toxicity, as well as the dermatologic, growth. Of note, there are receptors for retinoic acid located on and osteoclasts. (23) 8. Cho DY, Frey RA, Guffy MM, Leipold HW. Hypervitaminosis in the dog. Am J Vet Res. 1975;36:1597-1603. Alkaline Phosphatase 369 241 106-315 IU/L H 9. De Luca F Uveda JA Mericq V Mancilla EE Yannovski JA Barnes KM Zile MH Baron J. Retinoic acid is potent regulator of growth plate chondrogenesis. hematologic, and neurologic manifestations of vitamin A toxicity are well Endocrinology 2000;141:346-353. LDH 569 267 246-448 IU/L 5 years In vitamin A excess, animals have a dose-dependent acceleration of the processes of bone growth (epiphyseal documented(table). Bone manifestations of acute vitamin A toxicity include 10. Kodaka TT Takaki H soeta S Mori R Naiot Y. Local disappearance of epiphyseal growth plates in rats with hypervitaminosis A J Vet Med Sci. 1998;60:815-821. ALT (SGPT) 31 50 2-30 IU/L cartilage sequences, resorption of bone, and appositional bone formation) (22, 9). “In the rat, mitoses appear fewer 11. Hough S Avioli LV Muir H Gelderblom D Jenkins G Kurasi H Slatopolsky E Bergfeld MA Teitelbaum SL. The effects of hypervitaminosis A on the bone and Case Report etretinate periosteal elevation reminiscent of Caffey’s disease. The bony impact of chronic vitamin A in childhood mineral AST 82 60 16-52 IU/L and cell division ceases over the course of a few days. Cells continue to mature and degenerate and are replaced by O was first reported by Toomey and Morrisette in 1947, (3) when deep, hard, tender, extremity swellings were metabolism of the rat. Endocrinology 1988;122:2933-2939. This 6-year-old, Caucasian boy with a history of hypervitaminosis A was referred to us for evaluation of “epimetaphyseal GGT 145 13 8-55 IU/L O bone, causing” (22) reduced columnar zone depth. The chondrocytes lack hypertrophic morphology. (6) There is also 12. Soeta S, Mori R, Kodaka T, Naito Y, Taniguchi K. Immunohistochemical observations on the initial disorders of the epiphyseal growth plate in rats induced by high dose of vitamin A. J Vet Med Sci. 1999;61:233-238. Protein: Total Ser 5.5 6 5.3-8.0 g/dL O observed, and radiographs showed cortical thickening of tubular bones. These swellings resolved when oleum bone disease”. He had been a full-term, 10 lb 3 oz baby delivered with his father as a midwife to a 32 year-old, G7 P5-6 a decreased number of osteoblasts. Segmentated metaphyseal plates are partially replaced by immature bony 13. Standeven AM, Davies PJ, Chandraratna RA, Mader DR, Johnson AT, Thomazy VA. -induced epiphyseal plate closure in guinea pigs. Fundam Appl Toxicol A1 woman who had received prenatal vitamins but no prenatal care. Weaning from nursing began at age 11 months to a Albumin 2.9 30 2.9-4.5 g/dL percomorphum stopped, and recurred when the patient was fed pure vitamin A. By 1950, 14 cases had been trabeculae. Six months after withdrawal, growth plates had completely ossified and disappeared centrally. (7, 5) 1996;34:91-98. soy-based formula, which he drank until ~ 16 months of age. Baby food was introduced at 6 months of age. Early Ca / Creat 252 < 230 mg/gCr published with radiographic documentation of periosteal reactions and hyperostoses in infants and children from 14. Pease CN. Focal retardation and arrestment of growth of bones due to vitamin A intoxication. JAMA. 1962;182:980-985. Phos / Creat 1.57 0.5-1.5 g/gCr 15. Ruby LK Mital MA. Skeletal deformities following chronic hypervitaminosis A; a case report. J Bone Joint Surg Am. 1974;56:1283-1287. developmental milestones were on time (smiled at 6 weeks, rolled over at 4 months, sat up at 5 months, walked at 10 poisoning with vitamin A. (4) 16. Milstone LM McGuire J Ablow RC. Premature epiphyseal closure in a child receiving oral 13-Cis-Retinoic-Acid. J Am Acad Dermatol. 1982;7:663-666. months, talked at 18 months). At approximately 10 months of age, a bout of vomiting and diarrhea was reportedly treated 5) What are tolerable levels of vitamin A intake? 17. McGuire J Milstone L Lawson J. Isotretinoin administration alters juvenile and adult bone. in New Trends in Research and Therapy. Saurat (ed.) Retinoid Symp. The selective premature fusion of the growth plates seen in our patient is reminiscent of what has unfortunately been called Karger Basel Geneva 1984;419-439. by a chiropractor with four capsules of vitamin E, as well as vitamin A, vitamin C, a , and echinacea. At 15 Upon referral to us at age 6 years, he reported one hour of morning stiffness and bilateral knee and ankle pain. He The upper limit of vitamin A intake for children up to 3 years of age is 600 micrograms per day (2,000 international 18. Prendiville J Bingham EA Burrows D. Premature epiphyseal closure—a complication of etretinate therapy in children. J Am Acad Dermatol. 1986;15:1259-1262. “hyena disease” (closure of femoral and tibial growth plates with continued growth in radii and ulnae) seen in cattle exposed 19. Marini JC Hill S Zasloff MA. Dense metaphyseal bands and growth arrest associated with isotretinoin therapy. Am J Dis Child. 1988;142:316-318. months of age, he also reportedly began a calcium supplement with vitamin D. The dose of vitamin A reportedly was complained of cold intolerance, poor appetite, difficulty swallowing, shortness of breath, easy bruisability, easy losing units per day). (24) A meta-analysis of 259 case reports of vitamin A toxicity showed the “safe upper single dose” of to excessive doses of vitamin A and vitamin D. (5,6,7) This condition has been replicated in dogs (8), rats (9, 10, 11, 12), and 20. Ecklund K Jaramillo D. Patterns of premature physeal arrest: MR imaging of 111 children. AJR Am J Roentgenol. 2002;178:967-972. 300,000 units the first day, followed by a taper (a total of 3.06 million units in 16 days). He then reportedly continued to temper, anemia, and bleeding tendency. He was still being followed elsewhere by a hepatologist, continued to take water miscible, emulsified or dried preparation of retinol was 0.4 – 0.6 mg (1300 international units to 2000 21. Peterson HA. Physeal and apophyseal injuries. In: Rockwood J, Wilkins KE, Beaty JH, eds. Fractures in children,3rd ed. Philadelphia: Lipincott-Raven, 1996:103- guinea pigs (13). In 1962, the first description of this problem in children was a report of 7 patients with growth retardation 165. receive 60,000 units of vitamin A per day until he then developed a runny nose. This, and each subsequent possible sign vitamin K under their recommendations, and had liver biopsy proven fibrosis. The family had resumed treatment by a international units) per kilogram body weight, with thresholds not varying with age. Chronic hypervitaminosis A was from vitamin A toxicity, 3 of whom had premature closure of physes (14). Early reports of vitamin A-induced physeal toxicity 22. Wobach SB. Vitamin-A deficiency and excess in relation to skeletal growth. J Bone Joint Surg Am. 1947;29:171-192. of illness, reportedly prompted another tapering dose starting at 300,000 units each time. His parents estimated that he chiropractor ½ year prior to referral for adjustments only, with no medications or vitamins dispensed. He took hot baths induced by doses as low as 0.2 mg/kg/d. The retinol in oil or liver is ~ 10 times less toxic. (25) 23. Rohde CM DeLuca H. Bone resoprtion activity of all-trans retinoic acid is independent of vitamin D in rats. J Nutr 2003;133:777-783. received a tapering dose monthly for minor illnesses, but he was not sickly until age 2½ years of age. By age 2-9/12, he for leg pains and Echinacea. were, however, somewhat unclear because the animals as well as the patients had received both vitamin A and vitamin D. 24. National Academy of Sciences on dietary reference intakes (DRIs). Dietary reference intakes for vitamin A, vitamin A, arsenic, boron, chromium, copper, iodine, iron, Nevertheless, in 1974, vitamin A was implicated as the toxic precipitant of this radiographic finding. Distal femoral epiphyses manganese, molybdenum, nickel, silicon, vanadium, and zinc. January 09, 2001. is estimated to have received 89.7 million units of vitamin A. 25. Myhre AM Carlsen MH Bøhn SK Wold HL Laake P Blomhoff R. Water-miscible, emulsified, and solid forms of retinol supplements are more toxic than oil-based His past medical history was remarkable for having no immunizations, and not having seen a dentist. and proximal tibial epiphyses were described as being impressed into a cup-shaped irregular metaphyses following chronic preparations. Am J Clin Nutr 2003;78:1152-1159. At 22 months of age, he developed nosebleeds of increasing frequency. He remained quiet in his crib, perhaps having hypervitaminosis A alone. Further reports of vitamin A (15) and vitamin A analog (16, 17, 18) induced physeal closure have 6) Do individuals have varying susceptibilities to vitamin A toxicity? 26. Doireau V Macher MA Brun P Bernard O Loirat C. [Vitamin A poisoning revealed by hypercalcemia in a child with failure] [Article in French] Arch Pediatr. Family History: There was no consanguinity. His parents were both ~ 85% in height, and in good health. He had 8 1996;3:888-890. developed headaches. He began to regress at about 24 months of age, and became unsteady while walking with since been published. Of interest, co-treatment with a antagonist can block the toxic effects of retinoic 27. Ellis JK Russell RM Makrauer FL Schaefer EJ. Increased risk for vitamin A toxicity in severe hypertriglyceridemia. Ann Intern Med. 1986;105:877-879. increased falling. 7 months later he was no longer able to walk. siblings, one of whom had died at 12 months of age from congestive heart failure due to a hemangioma. A younger acid on hypertrophic chondrocytes in rats, thus reestablishing longitudinal bone growth and producing an accelerated growth Individuals with hepatopathy, hyperlipidemia, or renal failure (26) are at increased risk for vitamin A intoxication (27). 28. Molotkov A Fan X Duester G. Excessive vitamin A toxicity in mice genetically deficient in either dehydrogenase Adh1 or Adh3. Eur J Biochem. brother had reportedly also received high doses of vitamins but took only a few doses. He reportedly had no medical 2002;269:2607-2612. rate as compared to controls. Coadministration of vitamin D confers a protective effect in dogs. (8) There may also be a genetic predisposition to 29. Carpenter, TO Pettifor, JM Russell RM Pitha J Mobarhan S Ossip MS Wainer S Anast CS. Severe hypervitaminosis A in siblings: evidence of variable tolerance to At 24 months of age, he developed sores in his mouth that looked like blisters and bled. problems. There was deforming arthritis in a paternal grandmother but no other bone or joint diseases. vitamin A toxicity. Only 1% of calves raised on a farm where the vitamin A intake was 40 times recommended retinol intake. J. Pediat. 1987;111: 507-512. developed “Hyena disease”. Mice engineered deficient in alcohol dehydrogenase, Adh1 or Adh3, are especially 30. Schurr D Herbert J Habibi E Arahamov A. Unusual presentation of vitamin A intoxication. J. Pediat. Gastroent. Nutr. 1983;2:705-707. At about 27-28 months, he stopped eating table food, took only a bottle, and stopped gaining weight. He developed shiny 31. Pittsley RA Yoder FW. Retinoid hyperostosis. Skeletal toxicity associated with long-term administration of 13-cis-retinoic acid for refractory ichthyosis. N Engl J Med Physical examination at age 6 years, showed height of 5th percentile, weight 75th percentile, sitting height 50th predisposed to vitamin A toxicity (28). In fact, there have been two reports of families who seem to have a recessive 1983;308:1012-14. skin, fingernails that bubbled up and peeled off, and hair loss. Teeth stopped erupting (he had only six baby teeth at age percentile, arm span 75th percentile, and head circumference of >> 95th percentile. He was a well-appearing dysmorphic 2) Are these effects on the physeal plate reversible? 32. Ortega JJ Madero L Martin G et al. Treatment with all-trans retinoic acid and anthracycline monochemotherapy for children with acute promyelocytic leukemia: a disorder of increased susceptibility to vitamin A toxicity (29,30). multicenter study by the PETHEMA Group. J Clin Oncol 2005;23:7632-7640. 2 and 9/12). boy with a very high forehead, a large head, and multiple telangiectasias on his face (Fig). He had cupping of his optic 33. Reynolds CP Matthay KK Villablanca JD Maure BJ. Retinoid therapy of high-risk neuroblastoma.Cancer Lett 2003;197:185-192. disc and splenomegaly measuring 17cm in span without hepatomegaly. His musculoskeletal exam revealed a small oral Narrowing of growth plates from isotretinoin can sometimes resolve (19), but two year follow- up of physeal changes in our 34. Seibert JJ Byrne WJ Golladay ES. Development of hypervitaminosis A in a patient on long-term parenteral hyperalimentation. Pediatr Radiol. 1981;10:173-174. At 2 8/12 years of age, his eyes started to look yellowish and bulging, and he could not pick himself up. Notes from the aperture (3.2cm), bilateral 30º knee flexion contractures with fibular prominence, enlarged warm ankles and knees without patient indicate that reversal is not possible if vitamin A toxicity has been sufficiently severe. 35. Lam HS Chow CM Poon WT Lai CK Chan KC Yeung WL Hui J Chan AY Ng PC. Risk of vitamin A toxicity from candy-like chewable vitamin supplements for time of his hospitalization at age 2 9/12 years indicate he had an enlarged head, shiny, hairless skin, mouth sores and children. Pediatrics. 2006;118:820-4. erythema, and bowed tibias with a bowed stance. Skin revealed multiple petechia, bruises, and telangiectasias. 7) What is the prevalence of excessive vitamin A intake? 36. Shakeel M Little SA Bruce J Ah-See KW. Use of complementary and alternative medicine in pediatric otolaryngology patients attending a tertiary hospital in the UK. bleeding from the roof of his mouth, lips, nose, and ears, pseudotumor cerebri, coagulopathy, hair loss, ataxia, rash, Studies in guinea pigs (13) showed two patterns of physeal plate closure. In more severe cases, there were apoptotic Int J Pediatr Otorhinolaryngol 2007;71:1725-1730. chondrocytes. Osteoclasts were recruited to the growth plate, the cartilage was broken, and gaps were filled with trabecular 37. Soo I, Mah JK, Barlow K, Hamiwka L, Wirrell E. Use of complementary and alternative medical therapies in a pediatric neurology clinic. Can J Neurol Sci 2005;32: dramatically regressed milestones, icterus and hepatosplenomegaly. Vitamin A is essential for growth, sight, reproduction, and epithelial differentiation. Considerable attention has been 524-528. bone that was being formed without a cartilage template. Follow up, after cessation of vitamin A, showed the closure was given worldwide to ensure that vitamin A is given in adequate amounts to decrease the prevalence of blindness. In 38. Crawford NW, Cincotta DR, Lim A, Powell CV. A cross-sectional survey of complementary and alternative medicine use by children and adolescents attending the Laboratory findings at presentation elsewhere (Table) showed a coagulopathy, hepatitis, anemia, thrombocytopenia, but irreversible. (9) University Hospital of Wales. BMC Complement Altern Med 2006;6:16. the United States, vitamin A analogs are used to treat skin diseases (31,15,17) and cancer (32,33) 39. Rothenberg AB, Berdon WE, Woodard JC, Cowles RA. Hypervitaminosis A-induced premature closure of epiphyses(physeal obliteration) in humans and a normal calcium, , magnesium. An alkaline phosphatase was elevated at 827. Hypervitaminosis A was calves(hyena disease): a historical review of the human and veterinary literature.Pediatr Radiol. 2007;7:1264-1267. diagnosed and his vitamin supplements were stopped. His and were treated with PediaSure, A radiographic skeletal survey at 6 years of age revealed growth plate fusion in distal femurs, proximal tibiae, and distal four cans a day (each containing 610 units of vitamin A, 5.4 units of vitamin E). 1 1/2 months after discharge, at age 2- tibiae (the most rapidly growing physes), but not in other growth plates. Bone shaping and mineralization was otherwise 3) Our patient prematurely fused only lower extremity growth plates. Is there a selective effect of vitamin A on Elevated vitamin A levels have been found in patients with malabsorption syndromes (34) from over 10/12 years, he developed a cephalohematoma with a skull fracture and required three weeks of hospitalization with normal. Periosteal new bone formation was not seen, presumably having resolved much earlier. A comparison with different growth plates, or an increased susceptibility of some growth plates to any insult? supplementation. A risk of hypervitaminosis A from candy-like chewable vitamin use in children has also been multiple transfusions of Factor 7, fresh frozen plasma, and red blood cells (Fig). radiographs obtained 1 year earlier showed no significant change. There was a concern that increased bowing may occur Causes of premature physeal closure include trauma, infection, and tumor. A review of the pattern of premature physeal reported. (35) Perhaps more importantly, use of “complementary and alternative medicine” (CAM), including high Acknowledgments because the fibulae with open growth plates would continue to grow. arrest by MR imaging of 111 children was conducted in 2002 (20). Some anatomic sites seem to be particularly prone to doses of vitamins, has increased significantly over the last 20 - 30 years. More than 50% of the adult population in An MRI, at age 3, showed moderately large ventricles and a mild degree of elevated intracranial pressure. the United States uses dietary supplements. Estimates of CAM use in children include 29% (36) to > 40% (37,38), However, radiographs obtained 6 months later demonstrated closure of the proximal fibular epiphysis, a delayed effect growth arrest. Premature growth arrest was more common in the lower extremities than the upper extremities, regardless of We thank our patient and his family for his participation in our studies. Angelia English provided expert secretarial assistance. Vivienne with > 50% stating their family doctor was unaware. Bowing of his legs, first noted at age 3, became progressively worse. At 5 years of age, radiographs showed premature emerging considerably later than the vitamin A exposure. cause. Growth disturbance from non traumatic causes was more often proximal. In a large series of physeal fractures (21), Lim and Dawn Russell helped with illustrations. Supported by Shriners Hospitals for Children, The Clark and Mildred Cox Inherited closure of the growth plates (physes) in the distal femurs, proximal tibiae, and distal tibiae. Metabolic Bone Disease Research Fund and the Hypophosphatasia Research Fund.