|Year : 2017 | Volume
| Issue : 1 | Page : 227-233
Evaluation of cases of rickets that presented to the outpatient clinic of rickets in the National Institute of Neuromotor System in Giza
Ali M El Shafie1, Mohamed A Samir1, Zein O Abd El Latif1, Mohamed H El Sabagh2, Radwa G Mahmoud MBBCH 2
1 Department of Pediatric, Faculty of Medicine, Menoufiya University, Egypt
2 Department of Pediatric, National Institute of Neuromotor System, Shebin Elkom, Egypt
|Date of Submission||25-May-2016|
|Date of Acceptance||26-Jun-2016|
|Date of Web Publication||25-Jul-2017|
Radwa G Mahmoud
4 Sabri Abo Allam Street, Hamdy Kandil Buildings, Shebin El Kom
Source of Support: None, Conflict of Interest: None
The aim of this study was to assess clinical findings in different types of rickets, nutritional or resistant rickets.
Rickets is a metabolic disease of growth plate mineralization and ossification commonly occurring in children and adolescents. Vitamin D deficiency may result in bone diseases, such as rickets in children and osteomalacia and osteoporosis in adults.
Patients and methods
This study included 100 cases that presented with rickets in the rickets outpatient clinic of the National Institute of Neuromotor System. The initial search presented 100 cases of rickets aged from 4 months to adolescence. Cases less than 4 months of age or those above 18 years of age or with other bone diseases such as osteogenesis imperfecta, and hyperparathyroidism cases were excluded from the study. Comparisons were made by means of structured review with the results tabulated.
Of the 100 cases, 85% of cases were nutritional, whereas refractory rickets represented 15% of our cases. The incidence of refractory rickets was as follows: 26.7% hypophosphatemic rickets, 20% vitamin D-dependent type II, 20% vitamin D-dependent type I, 6.7% renal osteodystrophy, 13.3% renal tubular acidosis, 6.7% Fanconi syndrome, and 6.7% hypophosphatasia.
We found that the most common nonnutritional form of rickets was hypophosphatemic rickets. These results indicate the necessity to look for the diagnosis of renal tubular acidosis and hypophosphatemic rickets among children with rickets, especially in older-aged children, those with severe clinical features and poor response to therapy.
Keywords: hypophosphatemic, nutritional rickets, renal tubular acidosis, resistant rickets
|How to cite this article:|
El Shafie AM, Samir MA, Abd El Latif ZO, El Sabagh MH, Mahmoud RG. Evaluation of cases of rickets that presented to the outpatient clinic of rickets in the National Institute of Neuromotor System in Giza. Menoufia Med J 2017;30:227-33
|How to cite this URL:|
El Shafie AM, Samir MA, Abd El Latif ZO, El Sabagh MH, Mahmoud RG. Evaluation of cases of rickets that presented to the outpatient clinic of rickets in the National Institute of Neuromotor System in Giza. Menoufia Med J [serial online] 2017 [cited 2019 Aug 23];30:227-33. Available from: http://www.mmj.eg.net/text.asp?2017/30/1/227/211491
| Introduction|| |
Rickets is a metabolic disease of growth plate mineralization and ossification commonly occurring in children and adolescents .
Vitamin D deficiency may result in bone diseases, such as rickets in children and osteomalacia and osteoporosis in adults .
The source of vitamin D during fetal life and in the postnatal period is through placental passage, mother's milk, and synthesis in the skin by way of sunlight. Diet and sunlight determine the levels in the later months and years of life. On the basis of these facts, the insufficiency of vitamin D storage in mothers as well as exclusive breastfeeding without vitamin D supplementation constitute important risks for nutritional rickets in early life .
In rickets, severe lack of vitamin D3 is followed by inhibition of calcium absorption in the intestine, excessive phosphate and calcium excretion in the kidney, and consequently decrease in serum calcium concentration. In the aim to maintain proper calcium level, parathyroid hormone is secreted. It stimulates release of calcium from the bones. This process results in bone decalcification and subsequently symptoms of active rickets .
Rickets occurs in young children, and its first characteristic symptom is occipital malacia. Softening of the skull bones is usually recognized during palpation. In consequence of malacia, the occiput becomes flattened and the skull bones form a square shape with enlarged circumference .
In children who start to walk, varus or valgus deformities of the knees and also pelvis defects may occur. They may be accompanied by skeletal muscle flaccidity, which results in a delay in motor development, increase in abdominal circumference, abdominal distension, and constipation. The abovementioned early symptoms usually disappear in the later life. Late symptoms that remain in adulthood are flat feet, defects of the spine, and chest constriction .
Tetany is another rickets symptom. It results from hypocalcemia and is characterized by excessive electrical and mechanical excitability of the neuromuscular system and is followed by tonic cramps .
The initial phase of rickets is characterized by decreased serum concentration of vitamin D3 metabolite [25(OH)D3] and increased alkaline phosphatase activity, followed by increased excretion of phosphate in urine. In addition, in advanced rickets, a decreased level of serum phosphorus is observed. Calcium concentration is usually in the lower normal range. Prevention of rickets is based on the exposure to ultraviolet rays, and application of vitamin D3 preparations .
Vitamin D-dependent rickets (VDDR) type I is secondary to a defect in the gene that codes for the production of renal 25(OH)D3–1-α-hydroxylase. VDDR type II is a rare autosomal disorder caused by mutations in the vitamin D receptor .
Renal tubular disorders are an important cause of refractory rickets. In patients who are refractory to a replacement of vitamin D, a detailed search for other etiologies of rickets, such as hypophosphatemic rickets, including renal tubular acidosis, renal osteodystrophy, and vitamin D-resistant rickets, is warranted. Proximal renal tubular acidosis when accompanied by other proximal tubular defects such as glucosuria, aminoaciduria, uricosuria, and phosphaturia is referred to as Fanconi's syndrome and is a rare but important cause of short stature, such as caused by hypophosphatemic rickets. Fanconi's syndrome can either be a primary abnormality in the renal tubular cells or secondary to prerenal disorders in which toxic metabolic substances lead to the derangement of tubular functions such as cystinosis, Wilson's disease, tyrosinemia, galactosemia, and Lowe's syndrome .
Lowe syndrome (oculocerebrorenal syndrome of Lowe) is an X-linked, recessive disorder characterized by congenital cataracts, mental retardation, and proximal renal tubular dysfunction .
| Patients and Methods|| |
This study included 100 cases that presented with rickets in the rickets outpatient clinic of the National Institute of Neuromotor System.
Patients with different types of rickets aged from 4 months to adolescence were included in the study.
Patients younger than 4 months, those older than 18 years, those with other bone diseases such as osteogenesis imperfecta, and those with hyperparathyroidism were excluded from the study.
All studied infants were subjected to the following: history taking, physical examination, and laboratory investigations.
Motor developmental history included delayed sitting, teething, and walking.
One of the major indicators of motor development in a child is the age when the child starts to stand without support and walk .
Walking is considered to be delayed if it has not been achieved by 18 months .
Delayed tooth eruption is classified by the absence of any teeth by 13 months of age; possible causes of this include hypothyroidism, hypoparathyroidism, rickets, or idiopathic delayed eruption (most common) .
At this study, children with complaints of delayed walking, sitting, and teething were investigated for rickets by means of appropriate history, clinical examination, serum biochemistry, and radiology.
Exposure to sunlight
For how long does the mother expose her infant to sunlight?
One of the main sources of vitamin D is the endogenous synthesis from the skin 7-dehydrocholesterol by the action of ultraviolet B radiation. It was found that sunshine exposure either for 30 min/week of a naked infant wearing only a diaper or 2 h/week in fully clothed but without a hat was sufficient to prevent vitamin D deficiency irrespective of the maternal vitamin D status .
Family history of similar condition included bowlegs or other limb deformities.
Physiologic genu varum improves with growth, whereas pathologic bowing of the legs increases with skeletal growth .
Symptoms that develop with hypocalcemia are carpopedal spasm characterized by flexion of the hands at the wrists and of the fingers at the metacarpophalangeal joints and extension of the fingers at the phalangeal joints; the feet are dorsiflexed at the ankles and the toes plantar flexed .
VDDR patient complain of alopecia. Alopecia represents a form of end-organ resistance to 1,25-vitamin D . Approximately 50–70% of children have alopecia, which tends to be associated with a more severe form of the disease and can range from alopecia areata to alopecia totalis .
Genu valgum (knock-knees) is a condition in which the knees angle in and touch one another when the legs are straightened. The intermalleolar distance with the knees approximated is normally less than 2 cm, and in a severe valgus deformity it could measure more than 10 cm. Pathologic conditions leading to valgus are metabolic bone disease (rickets and renal osteodystrophy), skeletal dysplasia, post-traumatic physeal arrest, tumors, and infection .
Examination for signs of rickets was carried out.
The important clinical features searched for were as follows:
- Delayed closure of the fontanels
An infant has two fontanels at birth: a diamond-shaped anterior fontanel at the junction of the frontal and parietal bones that is open at birth, and a triangular posterior fontanel at the junction of the parietal and occipital bones that can admit the tip of a finger or may be closed at birth. The anterior fontanel varies greatly in size, but it usually measures ∼2 × 2 cm. The average time of closure is 18 months, but the fontanel can close normally as early as 9 months 
- Parietal and frontal bossing with caput quadratum: box-shaped skull
- Enlargement of the costochondral junction along the anterolateral aspects of the chest ('rachitic rosary'), which feels like the beads of a rosary as the examiner's fingers move along the costochondral junctions from rib to rib
- Harrison's sulcus groove at the lower margin of the thorax caused by muscular pull of diaphragmatic attachments to the lower ribs
- Sternum may be pulled into a pigeon-breast deformity
- Widening of the wrist (broad epiphysis) caused by growth plate widening
- Bowing of distal radius and ulna (coxa vera)
- Lateral bowing of the femur and tibia (genu valgum and varum)
- Double malleoli (Marfan's sign)
- Pot belly and vsisceroptosis .
Signs were as follows: delayed closure of the fontanels, rachitic rosary, Harrison's sulcus, broad epiphysis, Marfan's sign, and genu valgum and varum.
Measurement of weight and length
The measurement of length in children 2 years and younger is most accurate when two people can assist: one to position the child and one to measure. The child is placed supine on a measuring board, and the measurement should be reported to the nearest 0.1 cm.
In children older than 2 years, standing height rather than recumbent length was measured. The measurement was performed without shoes using a stadiometer and the head aligned so that the auditory canal and lower rim of the orbit were in a horizontal plane. Of note, length is about 1 cm greater than standing height .
The infant/toddler was weighed without clothing or diaper, and the measurement reported to the nearest 0.1 kg on a spring scale Laica Baby Scale 20 k (Laica, Italy). Older children's weight was measured without shoes and little/no outer clothing .
These measurements can also be plotted on Egyptian growth chart :
- Normal weight or length: for all cases their weight or length lies between third and 97th percentile
- Low weight or length: for all cases their weight or length lies below third percentile according to standard Egyptian growth charts 2015 .
Head circumference was measured. It was measured using a flexible tape measure at the maximum diameter through the supraorbital ridge to the occiput in the path that leads to the largest possible measurement .
- Total serum calcium using the colorimetric method.
- Serum alkaline phosphatase evaluation.
- Total serum phosphorus evaluation.
Radiography of the wrist and both lower limbs were obtained for all cases.
A structured systematic review was performed with the results tabulated [Table 1],[Table 2],[Table 3],[Table 4],[Table 5],[Table 6],[Table 7].
| Results|| |
We studied 100 patients, with a mean age of 2.42 years, who presented with rickets in the rickets outpatient clinic of the National Institute of Neuromotor System.
Our study showed that the most common cause of rickets was nutritional rickets (vitamin D deficiency rickets) representing 85% of cases, whereas refractory rickets represented 15% of our cases.
Refractory rickets in our study was represented as follows: 26.7% hypophosphatemic rickets, 20% vitamin D-dependent type II, 20% vitamin D-dependent type I, 6.7% renal osteodystrophy, 13.3% renal tubular acidosis, 6.7% Fanconi syndrome, and 6.7% hypophosphatasia.
| Discussion|| |
Our study showed that the most common cause of rickets was nutritional rickets (vitamin D deficiency rickets) representing 85% of cases, whereas refractory rickets represented 15% of our cases. Refractory rickets in our study was represented as follows: 26.7% hypophosphatemic rickets, 20% vitamin D-dependent type II, 20% vitamin D-dependent type I, 6.7% renal osteodystrophy, 13.3% renal tubular acidosis, 6.7% Fanconi syndrome, and 6.7% hypophosphatasia.
Thus, the most common nonnutritional form of rickets was hypophosphatemic rickets.
The findings of Alon  is in agreement with our results; he reported that the most commonly encountered nonnutritional form of rickets is familial hypophosphatemia.
Hypophosphatemic rickets was an important cause of refractory rickets in the Indian study by Bajipai and colleagues ,.
In contrast, Oduwole et al.  found that renal tubular acidosis was found in 38% of cases in Subsaharan Africa. These results are in disagreement with ours. Oduwole and colleagues aimed to determine the prevalence of idRTA among a cohort of participants with rickets to show a relationship between rickets and incomplete distal renal acidosis.
Our results showed that clinically the percentage of patients who had chest deformities at time of presentation was as follows: 20% had Harrison's sulcus and 19% had rosary beads.
Lower limb deformities in the form of bowlegs (genu varum) were very common (70%), whereas genu valgum accounted for 14% of cases. Broad epiphysis was present in 84% of patients, and Marfan's sign in 33% of our patients.
Anterior fontanel was abnormal in 9% of patients; they showed wide fontanel.
Hypotonia was present in 1% of cases.
Moreover, Agarwal et al.  showed symptoms of swollen wrists (76%) and bowlegs (48%) in their patients.
Al-Atawi et al.  documented the most frequent clinical signs in their patients to be wide wrist (29%), rachitic rosary (28%), wide anterior fontanel (15%), bowlegs (10%), and hypotonia (2%). These results are in disagreement with ours, specifically in terms of wide wrist and bowleg.
In contrast to our result, in another study, it was reported that rachitic rosary (62.1%) and enlargement of the wrists (27.1%) were the most common physical examination findings for the age group 0–6 months .
Moreover, Nadia  found swollen wrists in 38.3% of their patients and bowlegs in 28.3%, whereas Ladhani et al.  found swollen joints in three of the 65 patients (4.6%) and bowlegs in 15.3% in their retrospective study.
The study revealed that 59% of our patients were male and 41% were female. Moreover, in the study by Agarwal et al. , there were 25 patients with nutritional rickets. Of these, 15 were male (60%) and 10 were female (40%).
A study conducted at Alexandria University  on the vitamin D status of exclusively breastfed infants and their vitamin D stores in 120 infants suggested that there was no significant relationship between sex and infant vitamin D status.
Alopecia was present at diagnosis in two patients (2% of cases).
According to Orphanet, two-third of patients with VDDR have alopecia. Some children have alopecia either at birth or develop it in months after birth, which is an early sign of the disease and helps in the diagnosis especially in families that already have an affected child. In our study we observed two brothers who presented with alopecia totalis with vitamin D-dependent Type II.
Delayed walking was seen in 14% of patients and there was a high statistically significant difference between resistant and nutritional rickets; 26.7% of the resistant type complained of delayed walking (P < 0.0005).
Bowing was presented by 81% of our patients and there was a high statistically significant difference between resistant and nutritional rickets; 85.9% of cases of the nutritional type complain of bowing (P < 0.0005). Rickets is a disease of growing bone.
Rickets is the disease of a growing organism; therefore, the deformities and clinical findings are more specific to the bone tissue that is undergoing rapid growth at the age of onset of rickets ; hence, finally, in our study nutritional rickets cases presented more with bowing, whereas resistant rickets cases presented with delayed walking.
| Conclusion|| |
Rickets is not a disease only of the past, nor is it limited to developing countries. Rickets develops when growing bones fail to mineralize. In most cases, the diagnosis is established with a thorough history and physical examination and confirmed by laboratory evaluation.
Rickets is a preventable disease and prevention should start in pregnancy. The simplest measure for prevention is adequate sunlight exposure; however, in populations where this is impracticable or implausible, vitamin D supplementation should be instituted.
Vitamin D 400 IU per day is sufficient to maintain vitamin D status in the range in which adverse skeletal consequences are very unlikely, suggesting that a daily supplement ensures that irrespective of skin color, latitude, sunlight exposure, pollution, and societal or cultural pressures to cover up, the growing skeleton will get what it needs.
The most physiological method to prevent vitamin D insufficiency/deficiency is to educate society, and thus to ensure that mothers and infants are sufficiently exposed to sunlight and eat a balanced diet rich in calcium and vitamin D. Then again, detection of the maternal factors causing vitamin D insufficiency and taking measures to target these factors is essential in preventing cases of early rickets.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]