Case presentation
A 4-year-7month-old girl (currently 18-month-old girl) presented with hypotonia, weakness, impaired mobility, and poor growth. The patient had laboratory findings supporting hypocalcemia. Her hospitalization history was associated with severe shortness of breath noted by the impression of pneumonia. The patient was the second child in a family with a positive family history of metabolic disorders. She had never had a seizure before. The patient was delivered by cesarean section, weighed 3.3 kg at birth. There were no reports of miscarriage in the family history. The first child died of hypophosphatemic rickets. Perhaps her illness was misdiagnosed, resulting in a case of VDDR. Her parents were consanguineous and asymptomatic. The patient was normal regarding nutrition and perinatal care. The patient had no complaints of constipation and lost her appetite recently. Her weight and height were 8.800g and 73.5cm, respectively, both of which were below the 3rd percentile.
Examination of linear growth revealed a slow progression in height growth trend and inappropriate weight gain. Her developmental assessment noted that the patient was beginning to walk with assistance. Vision, cognition, perception, motor skills and expressive language comprehension were normal. At initial assessment; the patient was able to crawl and stand, and no pathological signs such as abnormal head circumference or impaired tooth development were observed. Her skull examination was normal. No evidence of alopecia was observed and hair distribution was normal. On her musculoskeletal assessment; her wrists were wide and her left ankle was slightly deviated. The patient was able to lift limbs in supine and upright positions. Pretreatment radiographs of her wrists and ankles were consistent with rickets. Muscle assessment; muscle weakness, reduced subcutaneous fat, and global hypotonia have been observed. Pathologic findings after patient exposure; small chest wall with normal expansion. Rachitic rosary was observed on her skin examination. Her chest inspection showed no harrison’s sulcus.
Laboratory profile at baseline; hemoglobin : 11.2 mg/dl, mean corpuscular volume : 75.7 fL, calcium : 8.9 mg/dl and Phosphorus: 3.4 mg/dl. Based on her symptoms, a treatment regimen was initiated according to her medical history and her first clinical evaluation; Rocaltrol capsule 0.25 microgram every 12 hours, Calmerz syrup 5 cc every 4 hours, PHOSPHATE SANDOZ tablet 500 mg every 6 hours, ferrous sulfate tablet 50 mg and folic acid 1 mg. After two months, she was referred to our center and treated with a diagnosis of hypophosphatemic rickets. On her next visit; she was mobile and had no problems for walking or running. The patient had a normal appetite and no history of constipation. The patient’s mental status was normal, and examination of the lower extremities showed no evidence of Coxa vara and Coxa valga. Her weight and height were and , respectively, both of which were below the 3rd percentile. Lab tests included PTH: 95.4 pg/ml, ferritin: 64 micg/L, ALP: 780 U/L, Hb: 11.7 mg/dl, MCV: 77.1 fL, thyroid stimulating hormone : IU/L, Free T4 m IU/L: 1.20, Ca: 10.2 mg/dl, phosphorus: 4.3 mg/dl and vitamin D: 25.7 ng/ml. Only Calmerz syrup was changed to 5 cc every 6 hours compared to her previous regimen.
At the next visit in 2 months; she had no trouble walking. She has no signs of a rachitic rosary. The patient has a normal appetite and does not complain of constipation. Also, she had flat feet and suffered from orthopnea. The patient’s weight and height were 9 kg and 77.5 cm, respectively, both of which were below the 3rd percentile. In her lab tests; PTH: 7.66 pg/ml, creatinine (Cr): 0.4 mg/dl, ALP: 343 U/L, Ca: 11.1 mg/dl, phosphorus: 5 mg/dl and vitamin D: 20.6 ng/ml. The patient’s diet was thus changed compared to the previous treatment regimen; PHOSPHATE SANDOZ 500 mg tablets every 6 hours, Calmerz syrup 5 cc every 8 hours and Rocaltrol capsule(5 capsules) every 12 hours. The patient complained of anorexia and polydipsia and was referred to our hospital one month later. Her mobility was acceptable and she had no problems with her gait. Evaluation of her renal and urinary tract ultrasound; Grade 3 hydronephrosis has been reported in her left kidney. Lab tests included; PTH: 22.1 pg/ml, ferritin: 79.6 micg/L, fasting blood sugar ( FBS): 88 mg/dl, 2-hpp glucose: 106 mg/dl, Bun: 44 mg/dl, Cr: 0.6 mg/dl, ALP: 337 U/L, Hb: 10.5 mg/dl, MCV: 71.5 fL, Ca: 10.3 mg/dl, phosphorus: 4 mg/dl, vitamin D: 36.1 ng/ml , growth hormone (GH): 4.3 IU/L and insulin-like growth factor 1 (IGF-1): 51 IU/L. The possibility of renal tubular acidosis (RTA) was ruled out based on no history of polyuria and normal blood potential of hydrogen (pH).
Vitamin D 1-alpha hydroxylase deficiency was suspected on the basis of clinical and laboratory findings, and balance according to therapy, and a complete exome sequencing (WES) plan was considered. The results was the known c.195 + 2T> G homozygous mutation in the CYP27B1 gene, which has an autosomal recessive inheritance. This mutation is located in exon 1 of chromosome 12q13 and is a Splice Site Pathogenic variant. Based on her clear diagnosis of VDDRIA and the patient’s symptoms, Rocaltrol capsules were administrated once in the morning and twice in the evening. PHOSPHATE SANDOZ 500 mg tablets were administered once every 8 hours, and vitamin D drops prescribed 2 drops daily. Calmerz syrup was also discontinued. The patient was followed up regularly and her symptoms improved. A follow-up radiograph showed her findings to be resolve. Due to persistent hydronephrosis during follow-up, periodic nephrology visits were considered. Her final weight and height were 10.8 kg and 89 cm, respectively, both of which were in the 3th percentile. She also had normal serum levels of vitamin D, calcium, phosphorus, and ALP. Her appetite was normal. She did not experience walking problem anymore.