INCIDENCE OF RICKET CLINICAL SYMPTOMS AND RELATION BETWEEN CLINICAL AND LABORATORY FINDINGS IN INFANTS

Rickets presents osteomalacia which is developed due to negative balance of calcium and / or phosphorus during growth and development. Therefore it appears only in children. The most common reason of insufficient mineralization is deficiency of vitamin D, which is necessary for inclusion of calcium in cartilage and bones. As result, proliferation of cartilage and bone tissue appears, creating calluses on typical places. Bones become soft and curve, resulting in deformities. Our present study included 86 infants, in whom, besides other diseases, clinical and laboratory signs of rickets were identified. In our study, rickets is most common (82.5%) in infants older than 6 months. By clinical picture, craniotabes is present in 46.5% of cases, Harisson groove in 26.7%, rachitic bracelets in 17.4%, rachitic rosary in 17.4% and carpopedal spasms in 2.3% of cases. Leading biochemical signs of vitamin D deficient rickets is hypophosphatemia (in 87.3% of cases), normal calcemia (in 75.6% of cases) and increased values of alkaline phosphatase (in 93% of cases). It has been shown that rickets in infant age may later affect higher incidence of juvenile diabetes, infection of lower respiratory tract, osteoporosis, and so on.


INTRODUCTION
Rickets is bone disease which leads to improper bone development in children due to insufficient mineralization [1,2].It is a multisystem disease with predominantly bone lesions.Osteogenesis is a complicated and dynamic complex of events in which calcium and phosphorus metabolism has a dominant role.These two elements are required for the construction of hydroxyapatite, which is deposited in the osteoid tissue and provides necessary rigidity for bones.The basic condition for normal homeostasis of calcium and phosphorus is optimal activity of the main metabolite of vitamin D (25-hidroxycalciferol and 1,25-hidrooxycalciferol) of parathyroid hormone (PTH), calcitonin and intact function of digestive system and kidneys.Presence of PTH is necessary for conversion of 25(OH)D to 1,25(OH)2D.Vitamin D needs are fulfilled through endogenous synthesis and food intake.Daily needs of vitamin D during growth and development period are 400 IU.Vitamin D amounts in food, especially in milk, are insufficient, so majority of physiological needs for this micronutrient is gained from photolysis of 7-dehydro-cholesterol in skin exposed to ultraviolet rays [3].Among innfants who live in areas with temperate and cold climate, and are not exposed to sunlight whole year, vitamin D production is often insufficient and does not satisfy needs of the organism, so in past these children often contracted rickets.Provitamin D is produced in liver from cholesterol and is deposited in the skin.Since the normal diet has a sufficient amount of calcium and phosphorus, pathogenesis of rickets is most often based on insufficient interstitial absorption of these two elements as a result of deficit in vitamin D and its metabolites [4].

Image 1. Craniotabes
In a rare clinical pictures, rickets develops as primary consequence of pathological loss of calcium and phosphorus through kidney.In clinical practice, the most often type of rickets is vitamin D deficient rickets, which is diagnosed in infants in second half of first year of life.Phosphatase rickets is rarer, and is consequence of excessive loss of phosphates through kidney, which is usu-ally hereditary disease.Important part of vitamin D deficiency rickets pathogenesis is insufficient photolysis of 7dehydro-cholecterol and a diet that favors malabsorption of calcium.This rickets type is more often in children with a darker skin tone, with insufficient sun exposure and in case of diet with unmodified cow's milk or diet with superabundance of grain intake.In our environment, cases of neonatal (congenital) rickets, due to vitamin D deficiency and osteomalacia through pregnancy, is not present.Rickets of premature infants is primarily caused by inadequate intake and by insufficient intestinal absorption of calcium and phosphorus due to immaturity, while resorption and activation of vitamin D remain intact.Vitamin D deficient rickets is rare in older children, primarily because of sufficient sunlight exposure, complete nutrition and lower growth rate [5].

Image 2. Rachitic rosary Image 3. Rachitic bracelets
Clinical picture of rickets is dominated by characteristic bone deformities as a result of osteomalacia and hyperplasia of osteiod tissue.The most often visible change is behavioral change with sweating, craniotabes, Harisson groove, rachitic rosary, rachitic bracelets and carpopedal spasms.
Reliable diagnosis of rickets can be set only if, at the same time, there are clincal, laboratory and radiographic signs of disease.Diagnosis is based on characteristic clinical findings and determination of calcemia, phosphatemia and alkaline phosphatase concentration, as well as the findings of x-ray that confirms bone changes.
Sufficient intake of vitamin D and adequate physical activity during growth period, from first year to end of adolescency, are only real prevention for this significant problem in children [6].This problem may be cause of severe osteophorosis in adulthood, whose treatment is expensive and uncertain.

THE AIM
The aim of this paper is to point to frequency of clinical symptoms and the relationship between clinical and laboratory findings of rachitic infants, as well as the importance of vitamin D prophylaxis implementation.

MATERIAL AND METHODS
The retrospective analysis included 86 infants hospitalized in the pediatric department of KBC Gracanica due to other diseases, that were diagnosed rickets based on clinical and laboratory findings.Medical history, clinical findings, laboratory tests (values of calcium, phosphorus and alkaline phosphatase) and skeletal radiography were used for diagnosis.
Vitamin D prophylaxis was conducted in 65,1% of infants, although even then children rarely received doses regularly and in optimal amount.

DISCUSION
Rickets occupies an important place in pathology of children in early age.Numerous statistics show different frequencies of disease.In early 20th century, rickets become major public health problem of industrial cities in Europe and America.It is disease of the whole organism due to disorder in metabolism of calcium and phosphorus, and is bound to deficiency of vitamin D. Although is rickets disease of different organs (muscles, lungs, nervous system), it is primarily disease of the skeleton, and that is main point of interest for us [7].In our country, most common and widespread type is vitamin D deficient rickets.Even today, in some areas presents social disease, and only if understood so can lead to proper prophylaxis.Any hypothesis to explain rickets should explain a few unquestionable facts: time of ricket occurence coincides with a period of maximum and intense growth, bone lesions which are especially affecting metaphysary zones of active bone growth and biologicaly variable syndroms such as calcemia and phosphatemia.Term "variability" is one ot the proof for the complexity of the rickets mechanisms.If we take only vitamin D deficiency and its impact on bone development, we wouldn't understand why children of given age, in same enviromental conditions, who haven't been taking vitamin D, don't have bone lessions and roughly the same biological disorders [5,8].The difference is huge.Some will have minimal radiological changes, other will have demineralised and disorted skeleton, some will be hypocalcemic, while other won't be.Futhremore, some children will be rachitic, others won't.We must accept that other etiological factors contributes to rickets being polymorphic and having varying degrees of intensity.
In addition to the deficiency of vitamin D, as important etiological factor, many other constitutinal and enviromental factors contribute to various aspects of rickets [9].In most traditional textbooks differences be-tween clinical presentation of vitamin D deficiency depending of age at which first symptoms appear are emphasized [10].Such divisions have more didactic importance, as sharp boundaries between certain types of vitamin D deficient rickets cannot be drawn.
The research included 86 infants with signs of rickets.Highest incidence of rickets (70.9%) were in children older than 6 months.Male children shows signs or rickets earlier.The changes are usually observed at the headcraniotubes are most often symptom, in 46.5% of cases, as consequence of osteomalacia and hyperplasia of osteoid tissue.Other common symptoms are rachitic rosaries (17.4%), which are consequence of osteoid thickening on crossing between cargtilage and bone in ribs, rachitic bracelets (17.4%), behavioral changes (irritability or reduced interest for enviroment) and sweating (40.7%), carpopedal spasms (2.3%).
Normocalcemia was found in 75.6% of cases, hypophosphatemia in 87.3% and increased values of alkaline phosphatase in 93.0% of cases.
Due to adequate therapy, vitamin D deficient rickets is rarely seen today in our society.

CONCLUSION
Our observations lead to conclusion that problem of vitamin D deficient rickets is still present in today pediatric practice.For proper early diagnosis of rickets full attention should be given to the symptoms that are more or less characteristic for this disease, as well as laboratory testing, primarily alkaline phosphatase in serum and values of calcium and phosphate, in order to timely apply appropriate therapy.Concern for children's health contribute to sucsessfull raising of future healthy generations.

Table 1 .
Incidence by age and sex

Table 3 :
Calcemia, phosphotamia and alkaline phosphatase values in examined infants