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Hypophosphatemic rickets, autosomal recessive, 1(ARHR1)

MedGen UID:
1632314
Concept ID:
C4551495
Disease or Syndrome
Synonyms: ARHR1; HYPOPHOSPHATEMIA, AUTOSOMAL RECESSIVE
 
Gene (location): DMP1 (4q22.1)
 
Monarch Initiative: MONDO:0009430
OMIM®: 241520

Definition

Hereditary hypophosphatemic rickets is a disorder related to low levels of phosphate in the blood (hypophosphatemia). Phosphate is a mineral that is essential for the normal formation of bones and teeth.

In most cases, the signs and symptoms of hereditary hypophosphatemic rickets begin in early childhood. The features of the disorder vary widely, even among affected members of the same family. Mildly affected individuals may have hypophosphatemia without other signs and symptoms. More severely affected children experience slow growth and are shorter than their peers. They develop bone abnormalities that can interfere with movement and cause bone pain. The most noticeable of these abnormalities are bowed legs or knock knees. These abnormalities become apparent with weight-bearing activities such as walking. If untreated, they tend to worsen with time.

Other signs and symptoms of hereditary hypophosphatemic rickets can include premature fusion of the skull bones (craniosynostosis) and dental abnormalities. The disorder may also cause abnormal bone growth where ligaments and tendons attach to joints (enthesopathy). In adults, hypophosphatemia is characterized by a softening of the bones known as osteomalacia.

Researchers have described several forms of hereditary hypophosphatemic rickets, which are distinguished by their pattern of inheritance and genetic cause. The most common form of the disorder is known as X-linked hypophosphatemic rickets (XLH). It has an X-linked dominant pattern of inheritance. X-linked recessive, autosomal dominant, and autosomal recessive forms of the disorder are much rarer.

Another rare type of the disorder is known as hereditary hypophosphatemic rickets with hypercalciuria (HHRH). In addition to hypophosphatemia, this condition is characterized by the excretion of high levels of calcium in the urine (hypercalciuria). [from MedlinePlus Genetics]

Clinical features

From HPO
Sensorineural hearing loss disorder
MedGen UID:
9164
Concept ID:
C0018784
Disease or Syndrome
A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.
Craniosynostosis syndrome
MedGen UID:
1163
Concept ID:
C0010278
Disease or Syndrome
Craniosynostosis refers to the premature closure of the cranial sutures. Primary craniosynostosis refers to the closure of one or more sutures due to abnormalities in skull development, and secondary craniosynostosis results from failure of brain growth.
Increased bone mineral density
MedGen UID:
10502
Concept ID:
C0029464
Disease or Syndrome
An abnormal increase of bone mineral density, that is, of the amount of matter per cubic centimeter of bones which is often referred to as osteosclerosis. Osteosclerosis can be detected on radiological examination as an increased whiteness (density) of affected bones.
Rickets
MedGen UID:
48470
Concept ID:
C0035579
Disease or Syndrome
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.
Hypophosphatemic rickets
MedGen UID:
309957
Concept ID:
C1704375
Disease or Syndrome
Rickets due to low serum phosphate concentrations, the cause of which can be nutritional or genetic. This condition is characterized by normal parathyroid hormone concentrations, usually caused by renal phosphate wasting occurring in isolation or as part of a renal tubular disorder, and characterized by resistance to treatment with ultraviolet radiation or vitamin D.
Hypophosphatemia
MedGen UID:
39327
Concept ID:
C0085682
Disease or Syndrome
An abnormally decreased phosphate concentration in the blood.

Professional guidelines

PubMed

Bai X, Levental M, Karaplis AC
J Clin Endocrinol Metab 2022 Sep 28;107(10):2777-2783. doi: 10.1210/clinem/dgac433. PMID: 35896139Free PMC Article

Recent clinical studies

Etiology

Ni X, Gong Y, Jiang Y, Li X, Pang Q, Liu W, Chi Y, Jiajue R, Wang O, Li M, Xing X, Xia W
J Clin Endocrinol Metab 2023 Mar 10;108(4):791-801. doi: 10.1210/clinem/dgac640. PMID: 36334264

Diagnosis

Ni X, Gong Y, Jiang Y, Li X, Pang Q, Liu W, Chi Y, Jiajue R, Wang O, Li M, Xing X, Xia W
J Clin Endocrinol Metab 2023 Mar 10;108(4):791-801. doi: 10.1210/clinem/dgac640. PMID: 36334264
Mercurio SA, Chunn LM, Khursigara G, Nester C, Wray K, Botschen U, Kiel MJ, Rutsch F, Ferreira CR
Hum Mutat 2022 Dec;43(12):1673-1705. Epub 2022 Oct 8 doi: 10.1002/humu.24477. PMID: 36150100
Bitkin EÇ, Aymelek HS
Turk J Pediatr 2022;64(3):585-591. doi: 10.24953/turkjped.2021.829. PMID: 35899574
Kato H, Ansh AJ, Lester ER, Kinoshita Y, Hidaka N, Hoshino Y, Koga M, Taniguchi Y, Uchida T, Yamaguchi H, Niida Y, Nakazato M, Nangaku M, Makita N, Takamura T, Saito T, Braddock DT, Ito N
J Bone Miner Res 2022 Jun;37(6):1125-1135. Epub 2022 Apr 11 doi: 10.1002/jbmr.4550. PMID: 35340077Free PMC Article
Brachet C, Mansbach AL, Clerckx A, Deltenre P, Heinrichs C
Horm Res Paediatr 2014;81(1):63-6. Epub 2013 Nov 6 doi: 10.1159/000354661. PMID: 24216977

Therapy

Bai X, Levental M, Karaplis AC
J Clin Endocrinol Metab 2022 Sep 28;107(10):2777-2783. doi: 10.1210/clinem/dgac433. PMID: 35896139Free PMC Article

Prognosis

Kato H, Ansh AJ, Lester ER, Kinoshita Y, Hidaka N, Hoshino Y, Koga M, Taniguchi Y, Uchida T, Yamaguchi H, Niida Y, Nakazato M, Nangaku M, Makita N, Takamura T, Saito T, Braddock DT, Ito N
J Bone Miner Res 2022 Jun;37(6):1125-1135. Epub 2022 Apr 11 doi: 10.1002/jbmr.4550. PMID: 35340077Free PMC Article

Clinical prediction guides

Kato H, Ansh AJ, Lester ER, Kinoshita Y, Hidaka N, Hoshino Y, Koga M, Taniguchi Y, Uchida T, Yamaguchi H, Niida Y, Nakazato M, Nangaku M, Makita N, Takamura T, Saito T, Braddock DT, Ito N
J Bone Miner Res 2022 Jun;37(6):1125-1135. Epub 2022 Apr 11 doi: 10.1002/jbmr.4550. PMID: 35340077Free PMC Article

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