Backround: Vitamin D dependent rickets type 1 (VDDR-1) is an autosomal recessive disorder caused by 1a hydroxylase enzyme deficiency, that leads to low or undetectable levels of 1,25 dihydroxyvitamin D despite normal levels of 25-hydroxyvitamin D levels. Additional laboratory findings include hypocalcemia and increased levels of parathyroid hormone. Clinically, it presents as early onset rickets and severe hypotonia.
Presenting problem: A 6-year-old Caucasian girl was referred to our Clinic after a 6 months history of hypotonia. Rickets was diagnosed at the age of 9 months, based on typical laboratory and radiological findings. Severe hypophosphatemia and generalized aminoaciduria were identified then. The levels of 25-hydroxyvitamin D were normal. She was started on 1α hydroxyvitamin D with prompt clinical and laboratory improvement. Under medication, the biochemical findings normalized and the child remained asymptomatic. That misled the parents into discontinuing treatment 3.5 years after diagnosis and for the next 2 years.
Clinical management: Physical examination on admission revealed genu valgum, short stature and generalized hypotonia. Laboratory workup revealed hypocalcemia, hypophosphatemia, marked elevation of alkaline phosphatase and parathormone, with normal levels of 25-hydroxyvitamin D and low levels of 1,25 dihydroxyvitamin D. Based on these findings and the fact that she had previously responded well to 1α hydroxyvitamin D, VDDR-1 was diagnosed. Awaiting genetic confirmation she was restarted on 1α hydroxyvitamin D. Biochemical and radiographic improvement was achieved within 3 and 6 months respectively.
Discussion: Clinical and radiological findings of VDDR-1 are indistinguishable from those of other forms of rickets. Distinction between the two can be based on characteristic biochemical findings. Normal levels of 25-hydroxyvitamin D exclude nutritional rickets, while normal serum calcium combined with elevated PTH excludes hypophosphatemic rickets.
Patients with DDR-1 should receive life long replacement treatment with 1α hydroxyvitamin D or calcitriol.
22 - 25 Jun 2013