Seizure as a presenting manifestation of vitamin D dependent rickets type 1.

There are two types of vitamin D dependent rickets (VDDR) that cause rickets in children. VDDR type 1 (VDDR-I) is caused by an inborn error of vitamin D metabolism, which interferes with renal conversion of calcidiol (25OHD) to calcitriol (1,25(OH)2D) by the enzyme 1-α-hydroxylase. Patients with VDDR-I have mutations of chromosome 12 that affect the gene for the enzyme 1-α-hydroxylase, resulting in decreased levels of 1,25(OH) vitamin D. Clinical features include growth failure, hypotonia, weakness, rachitic rosary, convulsions, tetany, open fontanels and pathologic fractures. We report a case of VDDR-I in 14-month-old male child. Establishing an early diagnosis of these genetic forms of rickets is challenging, especially in developing countries where nutritional rickets is the most common variety of the disease where genetic diagnosis is not always possible because of financial constraints. A prompt diagnosis is necessary to initiate adequate treatment, resolve biochemical features and prevent complications, such as severe deformities that may require surgical intervention.

INTRODUCTION

Rickets is still a common health problem and is considered to be a challenge even in developed countries. Epidemiological data are not available in many countries, etiology is sometimes difficult to establish and vitamin D supplementation and rickets treatment have been debated for a long time.

CASE REPORT

A child aged 10 months old was admitted in pediatric emergency department with focal seizures with secondary generalization. The child has, delay in motor developmental mile stones and hypotonia and poor gain in height. He had widening of wrist, potbelly, Harrison sulcus and rachitic rosary. Biochemical and radiologic signs were suggestive for rickets. Biochemical profile showing low serum calcium-6.1 mg/dl (9.2-11 mg/dl), low phosphorus-3.9 mg/dl (3.4-6.2 mg/dl), elevated alkaline phosphatase-4116 U/L (<269 U/L) parathyroid hormone was 233.6 pg/ml (15-65 pg/mL) 25-OH vitamin D was 40 ng/dl. Work-up for renal tubular acidosis was normal. Radiographic images of the wrist showed fraying and cupping of the distal radius and ulna, as well as bone demineralization; the metaphyses are widened, irregular and cupped. Physical examination, biochemical data (hypocalcemia, mild hypo-phosphatemia, high serum concentration of alkaline phosphatase) and rachitic changes on X-ray, were compatible with the diagnosis of rickets. The child was started on sodium valproate 20 mg/kg/day, calcium 500 mg/day and vitamin D 6 lakh IU following which there was no improvement in the serum calcium level and there was recurrence of seizures. Then endocrinologist opinion sought following which the child was initiated on 0.5 μg/day of active vitamin D (α cacidiol) along with 1000 mg of calcium. There was no seizure recurrence in the last 15 months and serum calcium normalized. In view of response to 1 α calciferol the diagnosis of vitamin D dependent rickets (VDDR) was made. Biochemical parameters and anthropometry on regular follow-up are shown in Table 1. 1,25 OH vitamin D and enzyme studies were not done in view of financial constraints and lack of availability.

Table 1

Anthropometry and biochemical parameters

DISCUSSION

VDDR usually manifests clinically during the 1st year of life. A total of 10 different allelic variants of VDDR have been identified, exhibiting little or no clinical differences.[1]

Prominent clinical manifestations of VDDR-I include growth failure, short stature, skeletal abnormalities, genu valgum, rachitic rosary, open fontanels, pathologic fractures, muscle weakness and convulsions.[234] Radiologic findings usually include fractures, generalized osteopenia, growth failure and arched or curved legs.[234] The most common laboratory findings include hypocalcemia, hypophosphatemia, elevated parathormone levels and high alkaline phosphatase.[234] Moreover, the serum levels of 25(OH) vitamin D are normal or raised while the levels of 1,25(OH) vitamin D are low or undetectable.[4]

Vitamin D is intimately involved in a wide variety of biologic processes, including calcium homeostasis, bone formation and cellular differentiation. In order to exert its effects, vitamin D must be activated by a metabolic pathway that requires the enzymatic activity of 25-hydroxylase and 1-α-hydroxylase.[56] VDDRI is inherited as an autosomal recessive disorder. The gene for VDDRI has been recently mapped to the long arm of chromosome 12, region one bands 2-4 (12q12-q14), representing the location of the 1-α-hydroxylase gene. A deficiency in the enzyme 1-α-hydroxylase causes a decrease in 1,25(OH)2 vitamin D production.[57] Hence, it has been suggested that the disease should be referred to as 1-α-hydroxylase deficiency.[57]

CONCLUSION

Stong clinical suspicion is required for the clinical diagnosis of VDDR and therapeutic challenge with 1 α calciferol will prove the diagnosis.