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.