Scurvy in infantile tremor syndrome
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《美国医学杂志》
Department of Pediatrics, Karnataka Institute of Medical Sciences, Hubli, Karnataka, India
Abstract
Infantile Tremor Syndrome is a distinct clinical entity most commonly seen in Indian Subcontinent. Syndrome consists of tremors, mental and developmental retardation, abnormal skin pigmentation and anemia in children between 6 months to 2 years. The etiology is still elusive. Amongst various theories, nutritional theory is the most accepted. So far there are no cases reported of vitamin C deficiency in ITS. In this article, three cases of ITS associated with vitamin C deficiency are reported.
Keywords: ITS; Etiology; Vitamin C
Infantile tremor syndrome (ITS) is a peculiar condition most commonly seen in Indian subcontinent.[1] Though it is a well known clinical entity, the etiology, pathogenesis and management of this condition remains obscure.[2] Amongst the theories proposed for the etiology of this disorder, the nutritional theory is most accepted. Many workers have tried to correlate the symptoms with certain trace of element deficiency states without satisfactory results.[3] Though vitamin C was used in treatment of ITS, there are no reported cases of scurvy in ITS. Herewith, the authors are presenting 3 cases of ITS associated with vitamin C deficiency.
Case Report
Case 1
A 17-month-old full term male child with exclusive breast feeding presented with history of tremors of hands and head-nodding and history of delayed milestones. On examination, the child weighed 6.5 kg (< 5th centile) and measured a length of 69 cm (< 5th centile). There was pallor, dry brown colored hair along with knuckle pigmentation. There was tenderness over thigh region bilaterally without other inflammatory signs. Respiratory system examination revealed bilateral crepitations and ronchi. Abdominal examination showed hepatomegaly, and CNS examination showed apathy, hypotonia and coarse tremors.
Investigation revealed anemia (Hb 5.8 gm %), reticulocyte count (1.5%) and MCV (99.5 Cum), MCH (33.8 mmg), MCHC (33.9%), RDW (11.4%) with the peripheral smear showing macrocytic picture. The work- up for tuberculosis and HIV was negative. Cerebrospinal fluid examination was normal. X-ray of knee showed ground glass appearance of bone, with pencil thin cortex, white line of Frankel at metaphysis and signet ring appearance at epiphysial centre Figure1.
Case 2
A 10-month-old male child presented with fever, cough and refusal of feeds for 10 days along with tremors of hands and feet. The child was alright till the 5th month after birth. History of delayed milestones was present. He was a term baby and exclusively breast fed till this admission. At the time of admission, the child was in altered sensorium with respiratory distress. On examination, the child weighed 5 kg (<5th centile) and measured a length of 70 cm (< 5th centile). There was significant pallor, dry brown colored hair and tenderness over thigh region, with hyperpigmentation over abdomen, hands and feet. Respiratory examination showed bilateral crepitations and ronchi. There was tender hepatomegaly. CNS examination revealed altered sensorium, hypotonia and coarse tremors. Investigation showed severe anemia (Hb 3.5 gm %), reticulocyte count of 0.5%, MCV 82.4 Cum, MCH 25.9mmg, MCHC 31.1%, RDW 13.1% with microcytic hypochromic picture. CSF examination, stool and urine examination was normal. There was no evidence of tuberculosis and HIV. X- ray of knee showed evidence of scurvy.
Case 3
A 12-month-old male child presented with delayed milestones, recurrent chest infections, tremors of hands and feet of recent onset. The child was exclusively breast fed till the admission date. On examination, the child weighed 7.5 kg (<5th centile) and measured a length of 75 cm (<5th centile). There was pallor, dry light brown colored hair with hyper pigmentation of abdomen, back, hands and feet. Investigation revealed anemia (Hb 9.4 gm %), MCV 104Cum, MCH 31.2mmg, MCHC 31% and RDW 18.6% with macrocytic picture. CSF, stool and urine examination was normal. The work-up for HIV and tuberculosis was negative. CT head was normal. X -ray of knee showed scurvy changes.
X-ray of knee was taken in the first two cases because of painful lower limbs, whereas for the third case, X-ray of knee was taken out of curiosity which also showed scurvy changes. In all the three cases, there were no other signs of scurvy. All three cases improved with the injection of vitcofol (contains folic acid and vitamin B12, vitamin C, high protein diet and antibiotics for chest infections. The second case required blood transfusion as the child was in severe anemia with congestive heart failure. The last two cases received propranolol for control of tremors for two weeks. All three received iron therapy after control of infection. They were discharged after 4 weeks of hospitalization with control of tremors and improvement in the nutritional status.
Discussion
ITS is characterized by coarse tremors, mental and physical retardation, light-colored brown hair, skin pigmentation and anemia in a plump child.[1], [2], [4], [5] ITS has been reported in infants and children between 5 months and 3 yrs of age. The peak incidence is between 9 and 18 months. Boys are more commonly affected than girls. Most of these cases are reported from low socioeconomic status. The exact incidence of ITS is not available. However, in various series 0.87 to 1.55 % pediatric ward admissions were due to ITS.[6] The clinical picture of all three cases was comparable to other cases described in literature.
In the present cases, the striking features noticed was: all the three had vitamin C deficiency signs on radiological examination. There are no reported cases of scurvy in ITS. It has been proposed that in our cases reported the association of vitamin C deficiency may be because of (i) exclusive breast feeding for long period, (ii) since many foods that contain vitamin C also contain folic acid, a diet that causes scurvy may also cause folic acid deficiency, (iii) ascorbic acid deficiency increases the oxidation of tetrahydrofolate to inactive folate metabolites and predisposes to macrocytic/megaloblastic anemia.[7]
Varying degree of anemia is always present in ITS. Peripheral smear shows a variable picture. Normocytic normochromic cells are observed in some, and microcytic in majority and macrocytic in others.[8] In the cases under study, two babies showed macrocytic picture and one showed microcytic anemia.
The management of ITS includes supplementation with vitamin B12 , iron, multivitamin, high protein diet and vitamin C.[9], [10] For control of tremors, many drugs have been tried including phenobarbitone, chlorpromazine, propranolol[11] with varying success. All our cases received injection Vitcofol, multivitamins and vitamin C apart from other appropriate care. Propranolol was given for 2 cases for 2 weeks with good response. The total duration required for control of tremors in all the cases was three weeks.
In view of the presence of scurvy, macrocytic and microcytic anemia, and good response to vitamin C and folic acid therapy, we feel that folic acid and vitamin C play significant role in the management of ITS.
References
1. Arya L S, Singh M, Aram G N, Farahmand S. Infantile tremor syndrome. Indian J Pediatr 1988; 55(6): 913-918.
2. Misra PK, Tandon PN, Bajpai PC. Infantile tremor syndrome - probable etiology. Indian Pediatr 1971; 8(2) : 62-64.
3. Agarwal R, Singh RN, Gupta BD, Agarwal DK,Arora AK. Serum magnesium, calcium, zinc in infantile tremor syndrome. Indian Pediatr 1993; 30(3) : 374-376.
4. Kaul KK, Prasan N, Chowdhary RM. Some clinical observation and impression on asydrome of tremors in infants from India. J Pediatr 1963; 63 : 1158-1166.
5. Garg BK, Srivastava JR. Infantile tremor syndrome. Indian J Pediatr 1969; 36 : 215-218.
6. Sharada B, Bhandari B. Infantile tremor syndrome. Indian Pediatr 1987; 24(5) : 415-421.
7. Bsoul SA, Terethalmy GT. Vitamin C in health and disease. J Contemporary Dental Practice 2004; 2 (5): 1-14.
8. Mahajan CM, Walia BNS and Parkash A. Anemia in Infantile tremor syndrome. Indian Pediatr 1971; 38 : 362-364.
9. Srikantiah SG, ReddyV. Megaloblastic anemia of infancy and vitamin B[12]. Br J Hematol 1967; 13 : 949-953.
10. Mathur GP, Dayal RS, Prasad R, Mathur S. Tremors , mental and physical retardation, light colored hair and anemia in malnourished children. Indian Pediatr 1969; 6: 483-487.
11. Kalra V, Marwaha RK. Propranolol in ITS. Indian J Pediatr 1981; 48(392) : 341-343.(Ratageri Vinod H, Shepur )
Abstract
Infantile Tremor Syndrome is a distinct clinical entity most commonly seen in Indian Subcontinent. Syndrome consists of tremors, mental and developmental retardation, abnormal skin pigmentation and anemia in children between 6 months to 2 years. The etiology is still elusive. Amongst various theories, nutritional theory is the most accepted. So far there are no cases reported of vitamin C deficiency in ITS. In this article, three cases of ITS associated with vitamin C deficiency are reported.
Keywords: ITS; Etiology; Vitamin C
Infantile tremor syndrome (ITS) is a peculiar condition most commonly seen in Indian subcontinent.[1] Though it is a well known clinical entity, the etiology, pathogenesis and management of this condition remains obscure.[2] Amongst the theories proposed for the etiology of this disorder, the nutritional theory is most accepted. Many workers have tried to correlate the symptoms with certain trace of element deficiency states without satisfactory results.[3] Though vitamin C was used in treatment of ITS, there are no reported cases of scurvy in ITS. Herewith, the authors are presenting 3 cases of ITS associated with vitamin C deficiency.
Case Report
Case 1
A 17-month-old full term male child with exclusive breast feeding presented with history of tremors of hands and head-nodding and history of delayed milestones. On examination, the child weighed 6.5 kg (< 5th centile) and measured a length of 69 cm (< 5th centile). There was pallor, dry brown colored hair along with knuckle pigmentation. There was tenderness over thigh region bilaterally without other inflammatory signs. Respiratory system examination revealed bilateral crepitations and ronchi. Abdominal examination showed hepatomegaly, and CNS examination showed apathy, hypotonia and coarse tremors.
Investigation revealed anemia (Hb 5.8 gm %), reticulocyte count (1.5%) and MCV (99.5 Cum), MCH (33.8 mmg), MCHC (33.9%), RDW (11.4%) with the peripheral smear showing macrocytic picture. The work- up for tuberculosis and HIV was negative. Cerebrospinal fluid examination was normal. X-ray of knee showed ground glass appearance of bone, with pencil thin cortex, white line of Frankel at metaphysis and signet ring appearance at epiphysial centre Figure1.
Case 2
A 10-month-old male child presented with fever, cough and refusal of feeds for 10 days along with tremors of hands and feet. The child was alright till the 5th month after birth. History of delayed milestones was present. He was a term baby and exclusively breast fed till this admission. At the time of admission, the child was in altered sensorium with respiratory distress. On examination, the child weighed 5 kg (<5th centile) and measured a length of 70 cm (< 5th centile). There was significant pallor, dry brown colored hair and tenderness over thigh region, with hyperpigmentation over abdomen, hands and feet. Respiratory examination showed bilateral crepitations and ronchi. There was tender hepatomegaly. CNS examination revealed altered sensorium, hypotonia and coarse tremors. Investigation showed severe anemia (Hb 3.5 gm %), reticulocyte count of 0.5%, MCV 82.4 Cum, MCH 25.9mmg, MCHC 31.1%, RDW 13.1% with microcytic hypochromic picture. CSF examination, stool and urine examination was normal. There was no evidence of tuberculosis and HIV. X- ray of knee showed evidence of scurvy.
Case 3
A 12-month-old male child presented with delayed milestones, recurrent chest infections, tremors of hands and feet of recent onset. The child was exclusively breast fed till the admission date. On examination, the child weighed 7.5 kg (<5th centile) and measured a length of 75 cm (<5th centile). There was pallor, dry light brown colored hair with hyper pigmentation of abdomen, back, hands and feet. Investigation revealed anemia (Hb 9.4 gm %), MCV 104Cum, MCH 31.2mmg, MCHC 31% and RDW 18.6% with macrocytic picture. CSF, stool and urine examination was normal. The work-up for HIV and tuberculosis was negative. CT head was normal. X -ray of knee showed scurvy changes.
X-ray of knee was taken in the first two cases because of painful lower limbs, whereas for the third case, X-ray of knee was taken out of curiosity which also showed scurvy changes. In all the three cases, there were no other signs of scurvy. All three cases improved with the injection of vitcofol (contains folic acid and vitamin B12, vitamin C, high protein diet and antibiotics for chest infections. The second case required blood transfusion as the child was in severe anemia with congestive heart failure. The last two cases received propranolol for control of tremors for two weeks. All three received iron therapy after control of infection. They were discharged after 4 weeks of hospitalization with control of tremors and improvement in the nutritional status.
Discussion
ITS is characterized by coarse tremors, mental and physical retardation, light-colored brown hair, skin pigmentation and anemia in a plump child.[1], [2], [4], [5] ITS has been reported in infants and children between 5 months and 3 yrs of age. The peak incidence is between 9 and 18 months. Boys are more commonly affected than girls. Most of these cases are reported from low socioeconomic status. The exact incidence of ITS is not available. However, in various series 0.87 to 1.55 % pediatric ward admissions were due to ITS.[6] The clinical picture of all three cases was comparable to other cases described in literature.
In the present cases, the striking features noticed was: all the three had vitamin C deficiency signs on radiological examination. There are no reported cases of scurvy in ITS. It has been proposed that in our cases reported the association of vitamin C deficiency may be because of (i) exclusive breast feeding for long period, (ii) since many foods that contain vitamin C also contain folic acid, a diet that causes scurvy may also cause folic acid deficiency, (iii) ascorbic acid deficiency increases the oxidation of tetrahydrofolate to inactive folate metabolites and predisposes to macrocytic/megaloblastic anemia.[7]
Varying degree of anemia is always present in ITS. Peripheral smear shows a variable picture. Normocytic normochromic cells are observed in some, and microcytic in majority and macrocytic in others.[8] In the cases under study, two babies showed macrocytic picture and one showed microcytic anemia.
The management of ITS includes supplementation with vitamin B12 , iron, multivitamin, high protein diet and vitamin C.[9], [10] For control of tremors, many drugs have been tried including phenobarbitone, chlorpromazine, propranolol[11] with varying success. All our cases received injection Vitcofol, multivitamins and vitamin C apart from other appropriate care. Propranolol was given for 2 cases for 2 weeks with good response. The total duration required for control of tremors in all the cases was three weeks.
In view of the presence of scurvy, macrocytic and microcytic anemia, and good response to vitamin C and folic acid therapy, we feel that folic acid and vitamin C play significant role in the management of ITS.
References
1. Arya L S, Singh M, Aram G N, Farahmand S. Infantile tremor syndrome. Indian J Pediatr 1988; 55(6): 913-918.
2. Misra PK, Tandon PN, Bajpai PC. Infantile tremor syndrome - probable etiology. Indian Pediatr 1971; 8(2) : 62-64.
3. Agarwal R, Singh RN, Gupta BD, Agarwal DK,Arora AK. Serum magnesium, calcium, zinc in infantile tremor syndrome. Indian Pediatr 1993; 30(3) : 374-376.
4. Kaul KK, Prasan N, Chowdhary RM. Some clinical observation and impression on asydrome of tremors in infants from India. J Pediatr 1963; 63 : 1158-1166.
5. Garg BK, Srivastava JR. Infantile tremor syndrome. Indian J Pediatr 1969; 36 : 215-218.
6. Sharada B, Bhandari B. Infantile tremor syndrome. Indian Pediatr 1987; 24(5) : 415-421.
7. Bsoul SA, Terethalmy GT. Vitamin C in health and disease. J Contemporary Dental Practice 2004; 2 (5): 1-14.
8. Mahajan CM, Walia BNS and Parkash A. Anemia in Infantile tremor syndrome. Indian Pediatr 1971; 38 : 362-364.
9. Srikantiah SG, ReddyV. Megaloblastic anemia of infancy and vitamin B[12]. Br J Hematol 1967; 13 : 949-953.
10. Mathur GP, Dayal RS, Prasad R, Mathur S. Tremors , mental and physical retardation, light colored hair and anemia in malnourished children. Indian Pediatr 1969; 6: 483-487.
11. Kalra V, Marwaha RK. Propranolol in ITS. Indian J Pediatr 1981; 48(392) : 341-343.(Ratageri Vinod H, Shepur )