Editorial note: In this case we have questioned the diagnosis the authors have made. The idea of this is not to criticize the efforts of the authors, but to point out an obvious flaw or error made in the diagnosis in this case. If you disagree with our explanation please feel free to send me an email on firstname.lastname@example.org
A 11 years old girl of a consanguineous parents belonging to a low socioeconomic status, hailing from Nazirabazar, Dhaka, was admitted at Dhaka Medical College Hospital on 07/03/07 with inward bending of both legs for last 4 years, not gaining height in comparison to other children of same age and dental caries for 2-3 years.
She had no history of polyuria, dysuria, jaundice, recurrent chest infections or recurrent attacks of diarrhoea and not on long term anticonvulsant drugs.
Q What is the importance of Polyuria in case of Rickets ?
- Polyuria with rickets is suggestive of Renal tubular acidosis, Barrter’s syndrome and certain cases of CKD.
Birth history was uneventful and was partially immunized as per EPI schedule. After birth she was predominantly breast fed for only 5 successive months and currently she is on family diet, i.e., rice, vegetable, fruits but low quantity of fish, meat, milk and egg as they are unable to afford those.
Q Are any of these good sources of vitamin D ?
- Since this case is from Bangladesh, food fortification status of general foods is not known.
- However, fatty fishes are good source of vitamin D , so the child may be receiving some vitamin D
Though her milestones of development were normal, her linear growth and also weight were not satisfactory as compared to that of other children of her age. Exposure to sunlight was adequate as she used to play along with other children in open air. Her father did not have the same disease and died of kidney disease two years back. Her mother and sibs are healthy
On examination, her pulse was 40/min, BP-100/60 mm Hg and temperature was normal.
Anthropometric measurement revealed height – 108 cm (74.2% of
NCHS median), weight – 18 kg (55.3% of NCHS median) and weight for height – 98.5% of NCHS median.
Both wrist and knee joints were widened , knocked knee was obvious on standing.
The chest examination demonstrated pegion chest deformity, mild rachitic rosary but there was no Harrison’s sulcus or other deformities of the limbs or joints.
However, dental caries were present in both upper and lower molar teeth
Radiologically, cupping, fraying and widening of growing lower ends of femur as well as radius and ulna, thinning of cortex and generalized osteopenia were revealed.
Q What are X-ray features of Hypophosphatemic rickets ?
- Hypophosphatemic rickets will show metaphyseal changes like widening and splaying, but calcipenic changes like fraying and osteopenia will not be seen.
- Sclerosis may be seen.
Laboratory investigations showed TC of WBC 8000/cmm, DC: polymorph 60%, lymphocyte 37%, monocyte 2%, basophil 1%, eosinophil 2%. Total platelet count was within normal range. Anisocytosis and poikilocytosis of RBC and mature WBC were showed in peripheral blood film.
Biochemical investigations showed near serum calcium (Ca++) level of 8.4 mg/dL (N: 8.8-10.8 mg/dL), serum phosphate 2.5 mg/dL (N: 4-7 mg/dL), while alkaline phosphatase was 630 IU/L which was much higher than normal range (N: 115-431 IU/L). Serum creatinine was 0.8 mg/dL and SGPT 40 IU/dL. The parathyroid hormone level was within normal limit 11 pg/mL (N: 7-53 pg/mL). Urine examination showed phosphaturia and its level was 24.5 mg/dL. Urinary creatinine was 22.5 mg/dL (N: 15-20mg/dL). As there is no definite range of the urinary phosphate level of 11 years old girl, tubular reabsorption of phosphorus (TRP) was calculated
The TRP was 68% (N: 78-98%) which confirmed loss of excess phosphate through urine. However, serum 1-α-hydroxylase level could not be done. All parameters of electrolytes were normal. Benedict’s test showed no glucosuria.
Both the clinical features and laboratory parameters were consistent with familial hypophosphatemic rickets.
Q Do you agree with the diagnosis ?
- Infact in my opinion the diagnosis in this case is most likely nutritional rickets due to vitamin D deficiency
Q What is the most important investigation that has been missed out in this analysis ?
- A 25-hydroxy- vitamin D level is not done.
Q What are the points in favour of this being a nutritional rickets ?
- Osteopenia in X-ray is a features of nutritional rickets and it is NOT seen in XLRH
- 25(OH) vitamin D is not obtained
- Serum calcium levels are low. XLRH patients generally have normal serum calcium levels.
Q if it is nutritional rickets, what explains the phosphate wasting ?
- Vitamin D deficiency typically produces secondary hyperparathyroidism.
- Increase PTH typically causes phosphate loss.
- The increase TRP can be very well explained by the secondary hyperparathyroidism.
Q You say it is secondary hyperparathyroidism , but the PTH levels is normal !
- PTH assay depends much on the transport.
- Improper transport of sample in cold chain can lead to reduction in PTH values and hence false low PTH.
- This is a well known fact and activation of thrombin is responsible for lowering of PTH values in the sample.
- Hence I believe that the PTH levels were false low.
Both the clinical features and laboratory parameters were consistent with familial hypophosphatemic rickets. So, she was treated with Joulie solution, an oral phosphate suspension made up of sodium phosphate (136 gm/L) and phosphoric acid (58.8 gm/L)5 1.5 tsf every 4 hourly. Active form of vitamine D (1-25 dihydroxy cholecalciferol) was also given in the form of Dicatrol capsule (0.25mcg) 6 hourly.
Along with treatment we consulted with orthopaedic department. She was advised to continue the treatment and for regular follow up. After 2 weeks of treatment with oral phosphate and dicatrol, significant radiological improvement was documented. Genetic counseling was also done. As the disease is X-linked, the defective gene may come either from father or from mother. Unfortunately, the genetic study is not possible in Bangladesh. As the father died two years back, there is no chance to have any more children.
Q So if the diagnosis was probably incorrect, why did the child respond to treatment ?
- The child was given active vitamin D supplementation.
- If the child truly has vitamin D deficiency as we are thinking, she would have responded to active vitamin D supplementation as well.
- When dealing with a case of rickets, it is always important to rule out common things first. Vitamin d deficiency (nutritional rickets) is far more common compared to other forms of rickets and must always be ruled out before further investigations are considered.
- Vitamin D deficiency with secondary hyperparathyroidism ALSO causes loss of urine phosphate and hence TRP will be reduced in such cases.