# Hypophosphataemia and X-Linked Hypophosphataemic Rickets

> Hypophosphataemia and X-linked hypophosphataemic rickets for NEET-PG Medicine, covering FGF23 excess, tumour-induced osteomalacia, lab patterns and burosumab.

- Canonical URL: https://prepelephant.com/topics/neet-pg/medicine/hypophosphataemia-and-x-linked-hypophosphataemic-rickets
- Exam / course: NEET-PG · Subject: Medicine
- Publisher: PrepElephant (https://prepelephant.com) — Prepared and reviewed by the PrepElephant Academic Review Team
- First published: 2026-10-14
- Last updated: 2026-10-14
- Reference basis: Williams Textbook of Endocrinology; Harrison's Principles of Internal Medicine
- How to cite: "Hypophosphataemia and X-Linked Hypophosphataemic Rickets", PrepElephant, https://prepelephant.com/topics/neet-pg/medicine/hypophosphataemia-and-x-linked-hypophosphataemic-rickets

## Direct answer

Hypophosphataemia is low serum phosphate, and its commonest inherited form, X-linked hypophosphataemic rickets, results from PHEX loss-of-function mutations that raise FGF23. Excess FGF23 causes renal phosphate wasting and inappropriately low 1,25-dihydroxyvitamin D, producing rickets in children and osteomalacia in adults. Raised FGF23 with inappropriate phosphate loss is the key laboratory pattern, and burosumab, an anti-FGF23 antibody, is now available.

## What you must remember

- **Mechanism:** FGF23 excess reduces sodium-phosphate cotransporter activity in the proximal tubule and suppresses 1-alpha hydroxylase.
- **Genetics:** XLH is caused by PHEX mutations and is inherited in an X-linked dominant pattern.
- **Lab pattern:** low or low-normal serum phosphate, normal calcium, raised alkaline phosphatase, inappropriately low 1,25-dihydroxyvitamin D and raised or inappropriately normal FGF23.
- **Tumour-induced osteomalacia:** a phosphaturic mesenchymal tumour secretes FGF23; the tumour is often small and hard to find, and resection usually corrects the biochemistry.
- **Clinical clues:** bowing of the legs, short stature, spontaneous dental abscesses and enthesopathy.
- **Conventional treatment:** oral phosphate with active vitamin D, monitored for nephrocalcinosis and secondary hyperparathyroidism.
- **Burosumab:** a monoclonal antibody against FGF23, given by subcutaneous injection, used in XLH and tumour-induced osteomalacia.

## Separating the causes on biochemistry

Low serum phosphate with bone disease in a child needs a clear separation between genetic, renal and tumour causes. The table sets out the main causes and their distinguishing features. Clinicians look at the urine as well as the blood, because the pattern of phosphate loss is what separates renal from tumour causes.

| Cause | Mechanism | Key clue |
|---|---|---|
| XLH | PHEX loss, so FGF23 excess | Family history, bowing, dental abscesses |
| Autosomal dominant hypophosphataemic rickets | FGF23 resistant to cleavage | Dominant inheritance, similar biochemistry |
| Hypophosphatasia (rickets mimic) | ALPL mutations, low ALP activity | Low alkaline phosphatase; phosphate normal or high |
| Tumour-induced osteomalacia | Phosphaturic tumour secreting FGF23 | Adult onset, fractures, tumour localisation |
| Fanconi syndrome | Proximal tubular dysfunction | Glycosuria and aminoaciduria |

Raised FGF23 with phosphate wasting points to XLH or a tumour, while low alkaline phosphatase points away from both towards hypophosphatasia. Measuring FGF23 alongside phosphate and alkaline phosphatase narrows the list quickly. Renal tubular disease is tested for separately, because glycosuria and aminoaciduria change the treatment plan.

## Where students lose marks

These points are repeatedly tested in biochemistry and paediatric medicine questions.

- **Trap:** treating XLH with calcium and vitamin D alone. — **Correct:** calcium and calcitriol do not correct renal phosphate loss, so phosphate supplementation is also needed.
- **Trap:** labelling every child with rickets-like bone disease as XLH. — **Correct:** hypophosphatasia, renal tubular causes and tumours must be excluded, since the alkaline phosphatase level, serum phosphate and urinary phosphate differ.
- **Trap:** missing a tumour in adult-onset osteomalacia. — **Correct:** raised FGF23 with adult hypophosphataemic osteomalacia should prompt a search for a phosphaturic mesenchymal tumour.

## Frequently asked questions

### What is the main laboratory pattern of X-linked hypophosphataemic rickets?

X-linked hypophosphataemic rickets shows low or low-normal serum phosphate, normal calcium, raised alkaline phosphatase and inappropriately low 1,25-dihydroxyvitamin D. Urinary phosphate loss is inappropriate for the low serum level, and FGF23 is raised. This pattern separates it from hypophosphatasia, where alkaline phosphatase is low.

### How does burosumab work in X-linked hypophosphataemia?

Burosumab is a monoclonal antibody that binds and neutralises FGF23. Blocking FGF23 restores renal phosphate reabsorption and raises 1,25-dihydroxyvitamin D. It is given by subcutaneous injection and is used in XLH and tumour-induced osteomalacia.

### Why does tumour-induced osteomalacia cause hypophosphataemia?

Tumour-induced osteomalacia occurs because a phosphaturic mesenchymal tumour secretes excess FGF23. This causes renal phosphate wasting and reduced active vitamin D, which leads to osteomalacia. Complete surgical removal usually corrects the biochemistry. The tumour can be small and hard to locate, so functional imaging is often used.

### How is hypophosphatasia distinguished from XLH on biochemistry?

Hypophosphatasia is distinguished from XLH by low alkaline phosphatase, whereas XLH has raised alkaline phosphatase. Hypophosphatasia results from ALPL gene mutations that reduce tissue-nonspecific alkaline phosphatase activity. Both can cause rickets-like bone disease, but phosphate is low in XLH and usually normal or high in hypophosphatasia, so the enzyme level is the key test.