ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2006) 12 OC14

The metabolic basis of a severe rickets-like deformity in Nigerian children

OA Couppis, W-K Emmert, K Kitz, W Van’t Hoff & WM Drake Stich

1St Bartholomew’s Hospitals, London, United Kingdom; 2Great Ormond Street Hospital, London, United Kingdom; 3Mission-Medical Institut, Würzburg, Germany.

A high prevalence of rickets in the Gbagyi tribe around Kaduna, Northern Nigeria, has been noted. Multiple affected children born to one wife, but not others, of polygamous men suggests a genetic aetiology.

With ethical approval, children with deformities characteristic of rickets (genu varum/valgum, rachitic rosary) were identified, clinical histories obtained and examination points documented included genu valgus/varus distances and other limb deformities.

Flash frozen serum from each family member was analysed for: serum corrected calcium, phosphate, alkaline phosphatase, albumin, 25(OH) and 1,25(OH)2 vitamin D (Diasorin RIA) and intact PTH (Nichols Advantage). Whole blood/EDTA was stored for genetic analysis. Data from 66 subjects (7 families) are presented and divided into the following groups: severely affected siblings (valgus/varum deformity >4 cm); unaffected siblings (no signs of rickets or varus deformity <4 cm); mildly affected cases (varus/valgus deformity <4 cm but another feature suggestive of rickets, e.g. bone pain at a young age); and parents.

Affected children demonstrated hypocalcaemia compared to unaffected siblings (1.9±0.3 mmol/l, vs 2.2±0.1 mmol/l, P=0.0003); higher PTH concentrations (27.1±11.8 vs 17.4±9.3 pmol/l, P=0.0001); and higher 1,25(OH)2 D concentrations (413.0±110.0 pmol/l, vs 266.0±102.0 pmol/l, P=0.0002). No differences between affected and unaffected siblings were noted in dietary intake of calcium.

The combination of hypocalcaemia, secondary hyperparathyroidism and significantly higher levels of 1,25(OH)2 D concentrations in affected children suggest a vitamin D receptor (VDR) defect, or an abnormality in vitamin D signalling as the cause of clinical rickets. 25(OH) D was comfortably within the reference range in all children, arguing against nutritional deficiency as the cause. Alopecia is commonly observed in rickets due to a VDR defect but was not observed here. Mutation analysis of the vitamin D receptor is currently in progress.

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