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PubMed This is a summary of 20 peer-reviewed journal articles Updated
Endocrinology

Long-Term Monitoring and Managing Complications

At a Glance

People with autosomal recessive hypophosphatemic rickets need lifelong, individualized monitoring of blood and urine tests, kidneys, bones, and, in the ENPP1-related subtype, heart, hearing, and vision to catch complications early.

Managing Autosomal Recessive Hypophosphatemic Rickets (ARHR) requires lifelong partnership with a multidisciplinary medical team. Because both the condition and its treatment can affect multiple organ systems, regular “surveillance”—monitoring for complications before they cause symptoms—is standard practice [1][2].

Monitoring the Effects of Treatment

The conventional treatment (oral phosphate and calcitriol) requires a careful balancing act. If doses are poorly balanced, they can cause specific complications:

  • Nephrocalcinosis and Stones: This is the buildup of calcium in the kidneys. In one small study of patients with ARHR2, roughly half developed nephrocalcinosis while on conventional therapy [3]. Doctors monitor this using regular renal ultrasounds and by testing the urine for a high calcium-to-creatinine ratio [4][5].
  • Hyperparathyroidism: If phosphate doses are high but vitamin D (calcitriol) is too low, the parathyroid glands may become overactive (secondary hyperparathyroidism). Over time, these glands can become permanently stuck in the “on” position (tertiary hyperparathyroidism), which worsens bone loss [6][5]. Regular blood tests for Parathyroid Hormone (PTH) are essential to catch this early [4].

Specialized Monitoring for ENPP1 (ARHR2)

Patients with ENPP1 mutations (ARHR2) face unique risks beyond bone health. In some reported cohorts, up to 70% of individuals with this subtype may develop complications outside the skeleton [7][8].

  • Cardiovascular Health: Calcium can deposit in the heart valves and arteries (ectopic calcification). Long-term care should include blood pressure monitoring and periodic echocardiograms or vascular imaging [9][10]. Your specialist will determine the exact imaging schedule based on genotype and symptoms, rather than a universal interval for everyone. Note that a normal echocardiogram cannot exclude vascular disease elsewhere.
  • Hearing and Vision: A lifetime risk of hearing loss as high as 75% has been estimated in select cohorts for those with ENPP1 deficiency [11]. Hearing tests (audiology) are recommended [12]. Occasionally, changes at the base of the skull can cause pressure in the head, requiring monitoring for papilledema (swelling of the optic nerve) [13].

Dental and Orthopedic Maintenance

  • Preventive Dental Care: Spontaneous dental abscesses (infections at the root) are a reported complication of ARHR, occurring even in teeth without cavities [14][15]. Patients should have individualized dental care plans and see a dentist who understands metabolic bone disease [2].
  • Orthopedic Alignment: While medical treatment helps heal the rickets, some patients develop persistent bowing or “twisting” of the legs that interferes with walking [16]. Orthopedic surgeons may use “guided growth” (small plates that gently straighten the bone as it grows) or osteotomies (surgically resetting the bone) to improve alignment [17][18].

Red Flags: When to Seek Immediate Care

Seek emergency evaluation promptly if you experience any of the following symptoms:

  • Spinal Cord Warning Signs: New limb weakness or numbness, balance problems, or sudden changes in bowel or bladder control. (Do not ignore these, as they may indicate OPLL, a hardening of a spinal ligament compressing nerves) [13][19].
  • Hypercalcemia Toxicity: Persistent vomiting, severe constipation, excessive thirst or urination, marked weakness, or sudden confusion.
  • Renal: Sharp pain in the side or back (flank pain) or blood in the urine, which may indicate a kidney stone [4].
  • Cardiovascular (ARHR2): Shortness of breath, unexplained fainting, severe chest pain, or sudden vision loss [7].

Sample Surveillance Checklist

(Note: Exact intervals are determined by your specialist.)

System Recommended Monitoring
Blood/Urine Phosphate, Calcium, PTH, Alkaline Phosphatase, and Vitamin D levels; Urine calcium/creatinine ratio [4][6].
Kidneys Regular renal ultrasounds to screen for nephrocalcinosis [3].
Heart (ARHR2) Periodic echocardiograms or vascular imaging as directed by phenotype; regular blood pressure checks [9][10].
Skeletal Growth tracking and X-rays of the legs to monitor rickets and alignment [4][20].
Sensory Periodic hearing tests and individualized preventive dental exams [11][2].

Common questions in this guide

What tests are used to monitor ARHR over time?
Your care team may check blood phosphate, calcium, parathyroid hormone (PTH), alkaline phosphatase, and vitamin D, along with urine calcium compared with creatinine. Kidney ultrasounds and, when appropriate, growth checks or leg X-rays look for treatment effects and changes in bone alignment. The timing is individualized, especially during growth or dose changes.
What is the purpose of kidney monitoring during ARHR treatment?
Oral phosphate and calcitriol can contribute to calcium buildup in the kidneys (nephrocalcinosis) or kidney stones if treatment is not well balanced. Urine calcium-to-creatinine testing and renal ultrasound help detect these problems early. Sharp flank pain or blood in the urine needs prompt medical evaluation.
Why does my doctor check PTH while I take phosphate and calcitriol?
If phosphate and calcitriol doses are not balanced, the parathyroid glands can become overactive, first causing secondary hyperparathyroidism and sometimes a lasting form called tertiary hyperparathyroidism. Regular PTH blood tests help the team adjust treatment and reduce the risk of worsening bone loss.
What extra screening is needed for ENPP1-related ARHR2?
ENPP1-related ARHR2 can affect more than the bones, so monitoring may include blood pressure checks, an echocardiogram or vascular imaging, hearing tests, and individualized evaluation of vision or pressure affecting the optic nerve. Your specialist sets the schedule based on the gene change and symptoms; a normal echocardiogram does not rule out blood-vessel disease elsewhere.
Which symptoms mean I should seek urgent care with ARHR?
Seek emergency evaluation for new weakness or numbness, balance trouble, or sudden bowel or bladder changes; these can signal pressure on the spinal cord. Persistent vomiting, severe constipation, excessive thirst or urination, confusion, flank pain, blood in the urine, shortness of breath, fainting, severe chest pain, or sudden vision loss also need prompt assessment.
Can ARHR cause dental problems even if I have no cavities?
Yes. Dental abscesses can occur in ARHR even when a tooth has no cavity, so preventive dental visits and an individualized care plan are important. Tell your dentist that you have a metabolic bone condition.
When might orthopedic surgery be considered for leg bowing in ARHR?
If leg bowing or twisting continues and interferes with walking despite medical treatment or bracing, an orthopedic surgeon may discuss guided growth or an osteotomy. The best option depends on growth status, bone alignment, symptoms, and the specialist’s assessment.

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Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.How frequently should we be doing blood and urine tests during this phase of growth (or treatment)?
  2. 2.What is our plan for monitoring my (or my child's) kidneys for calcium deposits (nephrocalcinosis)?
  3. 3.For ENPP1-related ARHR2, which specific cardiovascular tests (like an echocardiogram or blood pressure check) do you recommend for baseline and long-term screening?
  4. 4.Is my parathyroid hormone (PTH) level rising, and does our current dose of calcitriol need to be adjusted to prevent hyperparathyroidism?
  5. 5.Should we schedule a baseline hearing test or neuroimaging based on the specific gene mutation identified?
  6. 6.What are the criteria for considering orthopedic surgery versus continuing with bracing or medical management for leg bowing?

References

References (20)
  1. 1

    Optimizing diagnosis and management of patients with ENPP1 deficiency: an expert opinion.

    Bruno I, De Sanctis L, Foligno NE, et al.

    Journal of endocrinological investigation 2026; doi:10.1007/s40618-026-02843-1.

    PMID: 41770448
  2. 2

    Consensus Recommendations for the Diagnosis and Management of X-Linked Hypophosphatemia in Belgium.

    Laurent MR, De Schepper J, Trouet D, et al.

    Frontiers in endocrinology 2021; (12()):641543 doi:10.3389/fendo.2021.641543.

    PMID: 33815294
  3. 3

    Response of the ENPP1-Deficient Skeletal Phenotype to Oral Phosphate Supplementation and/or Enzyme Replacement Therapy: Comparative Studies in Humans and Mice.

    Ferreira CR, Kavanagh D, Oheim R, et al.

    Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 2021; (36(5)):942-955 doi:10.1002/jbmr.4254.

    PMID: 33465815
  4. 4

    Rickets guidance: part II-management.

    Haffner D, Leifheit-Nestler M, Grund A, Schnabel D

    Pediatric nephrology (Berlin, Germany) 2022; (37(10)):2289-2302 doi:10.1007/s00467-022-05505-5.

    PMID: 35352187
  5. 5

    Phosphatonins: From Discovery to Therapeutics.

    Kritmetapak K, Kumar R

    Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists 2023; (29(1)):69-79 doi:10.1016/j.eprac.2022.09.007.

    PMID: 36210014
  6. 6

    FGF23 and Associated Disorders of Phosphate Wasting.

    Gohil A, Imel EA

    Pediatric endocrinology reviews : PER 2019; (17(1)):17-34 doi:10.17458/per.vol17.2019.gi.fgf23anddisordersphosphate.

    PMID: 31599133
  7. 7

    Phenotypic characterization of ENPP1 deficiency: generalized arterial calcification of infancy and autosomal recessive hypophosphatemic rickets type 2.

    Ferreira CR, Hackbarth ME, Nitschke Y, et al.

    JBMR plus 2025; (9(5)):ziaf019 doi:10.1093/jbmrpl/ziaf019.

    PMID: 40176950
  8. 8

    Ectopic Calcification and Hypophosphatemic Rickets: Natural History of ENPP1 and ABCC6 Deficiencies.

    Ferreira CR, Kintzinger K, Hackbarth ME, et al.

    Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 2021; (36(11)):2193-2202 doi:10.1002/jbmr.4418.

    PMID: 34355424
  9. 9

    Autosomal recessive hypophosphatemic rickets type 2 due to ENPP1 deficiency (ARHR2).

    Edouard T, Linglart A

    Archives de pediatrie : organe officiel de la Societe francaise de pediatrie 2024; (31(4S1)):4S27-4S32 doi:10.1016/S0929-693X(24)00154-4.

    PMID: 39343470
  10. 10

    Autosomal recessive hypophosphatemic rickets type 2 (ARHR2): Is phosphate supplementation safe?

    Munteanu M, Rutsch F, Nitschke Y, et al.

    Bone 2026; (202()):117698 doi:10.1016/j.bone.2025.117698.

    PMID: 41176198
  11. 11

    Prospective phenotyping of long-term survivors of generalized arterial calcification of infancy (GACI).

    Ferreira CR, Hackbarth ME, Ziegler SG, et al.

    Genetics in medicine : official journal of the American College of Medical Genetics 2021; (23(2)):396-407 doi:10.1038/s41436-020-00983-0.

    PMID: 33005041
  12. 12

    Early onset hearing loss in autosomal recessive hypophosphatemic rickets caused by loss of function mutation in ENPP1.

    Steichen-Gersdorf E, Lorenz-Depiereux B, Strom TM, Shaw NJ

    Journal of pediatric endocrinology & metabolism : JPEM 2015; (28(7-8)):967-70.

    PMID: 25741938
  13. 13

    Base of Skull & Spinal Canal Narrowing in an Adolescent with Autosomal Recessive Hypophosphatemic Rickets Type 2.

    Gokul PR, Jarvis C, Kassab G, et al.

    Calcified tissue international 2025; (116(1)):20 doi:10.1007/s00223-024-01324-y.

    PMID: 39751914
  14. 14

    Expanding the Autosomal Recessive Hypophosphatemic Rickets Type I Carrier Phenotype and Adult Treatment with Burosumab.

    Sawalha NA, Sampaio ML, Liu D, et al.

    Calcified tissue international 2026; (117(1)).

    PMID: 41820620
  15. 15

    Oral assessment of patients with X-linked hypophosphatemic rickets.

    Buzato J, De Castro Santos VL, Botelho Pires de Campos MC, et al.

    Journal of the American Dental Association (1939) 2026; doi:10.1016/j.adaj.2026.03.002.

    PMID: 42047649
  16. 16

    Changes of the lower limb deformity in children with FGF23-related hypophosphatemic rickets treated with Burosumab: a single-center prospective study.

    Sawamura K, Hamajima T, Izawa M, et al.

    Journal of pediatric orthopedics. Part B 2024; (33(1)):90-96 doi:10.1097/BPB.0000000000001054.

    PMID: 36728857
  17. 17

    Persistent Lower Limb Deformities Despite Amelioration of Rickets in X-Linked Hypophosphatemia (XLH) - A Prospective Observational Study.

    Mindler GT, Stauffer A, Kranzl A, et al.

    Frontiers in endocrinology 2022; (13()):866170 doi:10.3389/fendo.2022.866170.

    PMID: 35399930
  18. 18

    Case Report and Review of Literature: Autosomal Recessive Hypophosphatemic Rickets Type 2 Caused by a Pathogenic Variant in ENPP1 Gene.

    Choe Y, Shin CH, Lee YA, et al.

    Frontiers in endocrinology 2022; (13()):911672 doi:10.3389/fendo.2022.911672.

    PMID: 35966073
  19. 19

    Chronic hypophosphatemia leading to the diagnosis of autosomal recessive hypophosphatemic rickets type 2 caused by a novel pathogenic variant in ENPP1.

    Tsai P, Maalouf NM

    Bone 2026; (213()):118086 doi:10.1016/j.bone.2026.118086.

    PMID: 42735739
  20. 20

    Approach to Hypophosphatemic Rickets.

    Ackah SA, Imel EA

    The Journal of clinical endocrinology and metabolism 2022; (108(1)):209-220 doi:10.1210/clinem/dgac488.

    PMID: 35981346

This page is for informational purposes only and does not constitute medical advice. Your ARHR specialist team should determine your monitoring schedule and evaluate warning signs, especially for a child or a person with ENPP1-related ARHR2.