X-linked hypophosphatemia

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

X-linked hypophosphatemia is characterized by low levels of phosphate in the blood (hypophosphatemia), which can lead to skeletal abnormalities. Phosphate is a mineral that is essential for the normal development of bones and teeth. Without adequate amounts of phosphate, the bones can weaken or soften, leading to a condition called rickets in growing children or a similar condition called osteomalacia in adults.

The features of X-linked hypophosphatemia vary widely, even among members of the same family. Mildly affected individuals may have hypophosphatemia without other signs and symptoms. More severely affected individuals typically experience slow growth beginning in early childhood, and they may be shorter than their peers. They often develop bone abnormalities that can impair movement and cause pain, such as legs that are abnormally curved (bowed) because the bones are too weak to bear weight. These abnormalities tend to worsen over time.

In adults with X-linked hypophosphatemia, osteomalacia can make the bones more prone to a type of fracture called a stress fracture, which can be painful. Affected adults may also have abnormal calcium deposits that occur near the joints where the ligaments and tendons attach (enthesopathy) and a painful joint disorder called osteoarthritis.

Other signs and symptoms of X-linked hypophosphatemia can include premature fusion of the skull bones (craniosynostosis) and hearing loss. Affected individuals may also have dental abnormalities, which can include pus caused by a bacterial infection (abscess). In rare cases, people with X-linked hypophosphatemia have abnormalities of the spine, which can include a narrowing of the spinal canal that can pinch the upper part of the spinal cord (spinal stenosis) and the formation of fluid-filled cysts (syrinx) within the spinal cord.

With early treatment, people with X-linked hypophosphatemia may have less-severe skeletal signs and symptoms and fewer long-term health issues.

ORPHANET DEFINITION A rare hereditary renal phosphate-wasting disorder characterized by hypophosphatemia, rickets and/or osteomalacia, and diminished growth.

Frequency in the source

From: MedlinePlus Genetics, National Library of Medicine

Point prevalence: 1-9 / 100 000; Norway; Value and class. Point prevalence: 1-9 / 100 000; United Kingdom; Value and class. Annual incidence: 1-9 / 100 000; Worldwide; Value and class. Point prevalence: 1-9 / 100 000; Worldwide; Value and class.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Elevated circulating alkaline phosphatase concentration · Very frequent (99-80%)

Abnormally increased serum levels of alkaline phosphatase activity.

Hypocalciuria · Very frequent (99-80%)

An abnormally decreased calcium concentration in the urine.

Hypophosphatemia · Very frequent (99-80%)

The concentration of phosphate ion in the blood circulation is below the lower limit of normal.

Renal phosphate wasting · Very frequent (99-80%)

High urine phosphate in the presence of hypophosphatemia.

Rickets · Very frequent (99-80%)

Rickets is divided into two major categories including calcipenic and phosphopenic. Hypophosphatemia is described as a common manifestation of both categories. Hypophosphatemic rickets is the most common type of rickets that is characterized by low levels of serum phosphate, resistance to ultraviolet radiation or vitamin D intake. There are several issues involved in hypophosphatemic rickets such as calcium, vitamin D, phosphorus deficiencies. Moreover, other disorder can be associated with its occurrence such as absorption defects due to pancreatic, intestinal, gastric, and renal disorders and hepatobiliary disease. Symptoms are usually seen in childhood and can be varied in severity. Severe forms may be linked to bowing of the legs, poor bone growth, and short stature as well as joint and bone pain. Hypophosphatemic rickets are associated with renal excretion of phosphate, hypophosphatemia, and mineral defects in bones. The familial type of the disease is the most common type of rickets.

Abnormality of lower-limb metaphyses · Very frequent (99-80%)

Abnormality of dentin · Frequent (79-30%)

Any abnormality of dentin.

Abnormality of epiphysis morphology · Frequent (79-30%)

An anomaly of epiphysis, which is the expanded articular end of a long bone that developes from a secondary ossification center, and which during the period of growth is either entirely cartilaginous or is separated from the shaft by a cartilaginous disk.

Arthralgia · Frequent (79-30%)

Joint pain.

Bone pain · Frequent (79-30%)

An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) localized to bone.

Bowing of the legs · Frequent (79-30%)

A bending or abnormal curvature affecting a long bone of the leg.

Bowing of the long bones · Frequent (79-30%)

A bending or abnormal curvature of a long bone.

Delayed ability to stand · Frequent (79-30%)

A failure to achieve the ability to stand up at an appropriate developmental stage. Most children begin to walk alone at 11 to 15 months of age. On average, children can stand while holding on at the age of 9 to 10 months, can pull up to stand and walk with one hand being held at 12 months, and can stand alone and walk well at 18 months.

Delayed ability to walk · Frequent (79-30%)

A failure to achieve the ability to walk at an appropriate developmental stage. Most children learn to walk in a series of stages, and learn to walk short distances independently between 12 and 15 months.

Other findings in the same source

From: Orphanet

Additional reported features include Disproportionate short stature (Frequent (79-30%)); Genu valgum (Frequent (79-30%)); Genu varum (Frequent (79-30%)); Growth delay (Frequent (79-30%)); Nephrocalcinosis (Frequent (79-30%)); Odontodysplasia (Frequent (79-30%)); Rachitic rosary (Frequent (79-30%)); Reduced bone mineral density (Frequent (79-30%)); Tooth abscess (Frequent (79-30%)); Upper limb metaphyseal widening (Frequent (79-30%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: MedlinePlus Genetics, National Library of Medicine

Childhood; Infancy

Inheritance in the source

From: MedlinePlus Genetics, National Library of Medicine

X-linked

Frequency and the population described

From: MedlinePlus Genetics, National Library of Medicine

Point prevalence: 1-9 / 100 000; Norway; Value and class. Point prevalence: 1-9 / 100 000; United Kingdom; Value and class. Annual incidence: 1-9 / 100 000; Worldwide; Value and class. Point prevalence: 1-9 / 100 000; Worldwide; Value and class.

Which doctor should you see?

The suggested department for discussing X-linked hypophosphatemia is Orthopaedics, with a orthopaedic specialist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• What explains the change in pain, movement or function?
• Which activities need adjustment while the diagnosis is being clarified?
• What are the roles of rehabilitation, observation and surgery in this situation?

Treatment discussions and follow-up

Where the source describes treatments, these are an overview of possible care, not a prescription for an individual. Ask which option applies to the confirmed diagnosis, what benefit is expected, what adverse effects to watch for and how progress will be assessed. Availability, approvals and local practice can differ from the country described in the source.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.