Rathbun syndrome has six forms: odontohypophosphatasia, adult monophasic and biphasic, childhood, infantile and perinatal [1]. The more early clinical signs appear, the more severe the disease is. Thus, an adult suffering from this condition may have no complaints other than a pathologic fracture, whereas a fetus with severe hypophosphatasia may be stillborn, with no mineralized bone tissue. Children with less severe forms lose their deciduous teeth earlier than normal, therefore a dentist may be the first to diagnose the disease. Infantile Rathbun syndrome cases present with complaints during the first six months of life, consisting of failure to thrive, rachitic chest, hypotonia, seizures, vomiting, constipation, poor feeding, weakness, respiratory complications, waddling gait or irritability [2]. Seizures may progress to severe epileptic encephalopathy but respond to vitamin B6 administration [3]. Bone deformities like metaphyseal cupping, craniosynostosis, brachycephaly or bowed and short limbs may be noticed and the child may learn how to walk later than his healthy peers. Intracranial hypertension follows head deformities and causes headaches, papilledema, and proptosis. The bone tissue has an increased risk of fracture and skeletal ossification is delayed. Rib deformities and fractures predispose to pulmonary disease, potentially progressing to life-threatening respiratory distress, especially in cases where the lungs are underdeveloped. Bone pain in affected children is often noticed [4].

In adults, the ailment may have a biphasic course, with mild symptoms during childhood that remain unnoticed and more severe signs during middle age or a monophasic pattern, with complaints appearing later in life. Patients have osteomalacia, metatarsal or femoral fractures due to decreased mineralization may lose their permanent teeth early. Spine fractures, as well as calcific periarthritis, chondrocalcinosis, pseudogout, and sterile osteomyelitis, have also been documented [5].

• Failure to Thrive

  Infantile Rathbun syndrome cases present with complaints during the first six months of life, consisting of failure to thrive, rachitic chest, hypotonia, seizures, vomiting, constipation, poor feeding, weakness, respiratory complications, waddling gait [symptoma.com]

  Other features in this inherited inborn error of metabolism include failure to thrive, movement disorders, and low plasma levels of alkaline phosphatase. HPP is an extremely variable disorder. [accesspediatrics.mhmedical.com]

  The initial problem may be the baby’s failure to gain weight and grow as expected, referred to as “failure to thrive.” Sometimes the skull bones fuse, called craniosynostosis, which can lead to a deformed head (brachycephaly). [rarediseases.org]

• Strabismus

  […] retardation Short stature Squint Telecanthus Premature closure of a skull bone Communicating hydrocephaly Corneal clouding Frontal bossing Corneal opacity Hypotonia Small jaw Recessed jaw Cognitive impairment Craniosynostosis Renal hypoplasia/aplasia Strabismus [checkorphan.org]

• Osteoporosis

  This is not the same as osteoporosis, another bone disorder that also can lead to bone fractures. [softbonescanada.ca]

  Your doctor might suspect other bone, joint, or teeth problems, like osteoporosis, arthritis, rickets, or gum disease. If your doctor doesn't think you have HPP, but their diagnosis doesn’t seem to fit, don't be afraid to get a second opinion. [webmd.com]

  Hadju–Cheney syndrome (OMIM 102500) Idiopathic juvenile osteoporosis Renal osteodystrophy Adult and odontohypophosphatasia Osteoarthritis and pseudogout Osteopenia/osteoporosis Diseases with paraspinal ligament ossification (Forestier disease, arthropathy [nature.com]

  Osteoporosis International. 28 (9): 2653–2662. doi:10.1007/s00198-017-4087-z. PMID 28547134. S2CID 25864719. ^ "Hypophosphatasia". NORD (National Organization for Rare Disorders). [en.wikipedia.org]

  Antibodies that act against sclerostin have been shown to increase bone mass in osteoporosis. For additional information regarding HPP contact: Michael P. [rarediseases.org]

• Irritability

  Infantile Rathbun syndrome cases present with complaints during the first six months of life, consisting of failure to thrive, rachitic chest, hypotonia, seizures, vomiting, constipation, poor feeding, weakness, respiratory complications, waddling gait or irritability [symptoma.com]

  May have trouble changing activities, resist redirection (disregulation, state rigidity), show irritability, stubbornness or repetitive speech or behavior (perseveration) as signs of distress. [come-over.to]

  […] reveal progressive improvement of the skeletal anomalies and mineralization during the third trimester of the pregnancy.12, 13 Clinical signs of the infantile form appear during the first 6 months of life, including rickets, premature craniosynostosis, irritability [nature.com]

Blood workup is especially important in Rathbun syndrome. Typical findings include decreased alkaline phosphatase level and increased phosphoethanolamine (now considered to be a non-specific finding) and inorganic pyrophosphate blood and urinary levels, as well as hypercalcemia [6]. The alkaline phosphatase value must be interpreted according to the patient's age; keeping in mind that decreased values can be encountered in other diseases too. Serum level of vitamin B6 must also be measured and will found to be elevated. Additional useful tests include magnesium, phosphorus, creatinine, vitamin D, and parathyroid hormone determinations.

Radiographic features of Rathbun syndrome can include premature closure of skull sutures, hyperostosis, calcific periarthritis and chondrocalcinosis [7]. Mineralization is often found to be diminished, in addition to pathological fractures, pseudofractures, stress fractures and rachitic changes. A renal ultrasound may reveal the presence of nephrocalcinosis. A bone biopsy, although seldom needed, can differentiate this disease from osteomalacia.

The diagnosis can be suspected before birth by ultrasonography and confirmed using ALPL gene analysis. Alkaline phosphatase can also be measured in the amniotic fluid and cultured amniotic cells.

In addition to taking asfotase alta, you or your child will have a care team who will come up with other treatments and lifestyle changes to help with symptoms. [webmd.com]

[edit] As of October 2015, asfotase alfa (Strensiq) has been approved by the FDA for the treatment of hypophosphatasia. [en.wikipedia.org]

Supportive treatments for HPP are directed toward specific symptoms and complications. Treatment may require a team of specialists. [rarediseases.org]

In February 1999, claimant sought medical treatment for wrist and elbow pain that was related to her work. [nycourts.gov]

The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment. [orpha.net]

Prognosis - Sommer Rathbun Battles syndrome Not supplied. Treatment - Sommer Rathbun Battles syndrome Not supplied. Resources - Sommer Rathbun Battles syndrome [checkorphan.org]

Conclusions: Patients with upper extremity DVT may be treated safely with either dalteparin sodium followed by warfarin or dalteparin sodium monotherapy for 3 months with a good prognosis. Enhanced PDF Standard PDF (153.3 KB) [onlinelibrary.wiley.com]

What’s the prognosis for me (or my child)? To get the most out of your visits, don’t be afraid to ask lots of questions. Ask your doctor to clarify anything you don’t understand. Keep a record of symptoms, tests, and surgeries. [webmd.com]

Prognosis The perinatal form is considered lethal. The infantile form is believed to be fatal in approximately 50% of patients. Longevity studies have not been conducted for the infantile and childhood forms. [emedicine.medscape.com]

Mundle Springer Science & Business Media, 06.12.2012 - 280 Seiten Myelodysplastic syndromes are to the bone marrow what pneumonia is to the lungs; the response of an organ to a variety of etiologic insults like aging, toxic exposure, infections and auto-immunity [books.google.de]

They are organised into groups, and further divided into clinical, etiological or histopathological sub-types. [orpha.net]

Many theories have been developed since the discovery of KTWS; however, the etiology of the syndrome is still unknown. [jmedicalcasereports.biomedcentral.com]

Etiological approach to characterization of diabetes type: the SEARCH for Diabetes in Youth Study. Diabetes Care. 2011; 34:1628–1633. Article PubMed PubMed Central Google Scholar Bell DSH and Ovalle F. [link.springer.com]

STONER, Biostatistics and Epidemiology, College of Public Health, University of Oklahoma Health Sciences Center Search for more papers by this author T. L. [onlinelibrary.wiley.com]

Epidemiology Frequency United States Incidence of the severe form is believed to be approximately 1 case per 100,000 live births. [2] In some inbred populations, such as Canadian Mennonites, the frequency is as high as 1 case per 2500 newborns. [emedicine.medscape.com]

Epidemiology Abacavir hypersensitivity has been reported in both children and adults. The incidence in clinical trials has a range of 0%–14% [ 7–18, 32 ]. [academic.oup.com]

"Epidemiological, Clinical and Genetic Study of Hypophosphatasia in A Spanish Population: Identification of Two Novel Mutations in The Alpl Gene". Scientific Reports. 9 (1): 9569. Bibcode:2019NatSR...9.9569G. doi:10.1038/s41598-019-46004-2. [en.wikipedia.org]

Pathophysiology Deficient activity of tissue-nonspecific alkaline phosphatase, one of the four isomers of alkaline phosphatase (each of which has its own gene locus). [accesspediatrics.mhmedical.com]

The pathophysiology of SPS involves the impairment of GABAergic neurotransmission. While 6 separate autoantigens have been identified,9 the presence of anti-GAD antibodies has been reported in 43%9 to 85%2,4 of patients. [link.springer.com]

In all probability, the intrinsic and the extrinsic theories coexist and explain the pathophysiology of rotator cuff degeneration. [emedicine.medscape.com]

"Pathophysiology of hypophosphatasia and the potential role of asfotase alfa". Therapeutics and Clinical Risk Management. 12: 777–786. doi:10.2147/TCRM.S87956. PMC 4876073. [en.wikipedia.org]

This is interesting for genetic counseling and may help to prevent/delay the onset of clinical symptoms. [nature.com]

Prevention - Sommer Rathbun Battles syndrome Not supplied. Diagnosis - Sommer Rathbun Battles syndrome Not supplied. Prognosis - Sommer Rathbun Battles syndrome Not supplied. Treatment - Sommer Rathbun Battles syndrome Not supplied. [checkorphan.org]

Prevention of pulmonary embolism and deep vein thrombosis with low dose aspirin: Pulmonary Embolism Prevention (PEP) trial. Lancet. 2000 Apr 15. 355(9212):1295-302. [Medline]. Prevention of thromboembolism in spinal cord injury. [medscape.com]

One of the other men who stepped in to prevent Rinder’s death said: “I, along with others, pulled Rathbun off of Rinder. He speaks of violence, there’s your violence.” [freedommag.org]

Scott 9800 – S E Sunnyside Clackamas, OR 97015 Phone: (503) 652-2880 Fax: (503) 571-3494 Contact: Richard Konkol, M.D. www.kaiser-permanente.org Prevention Programs, including Treatment for Women University of Washington – CARE/ Northwest Box 357920, [nofas.org]

1. Fraser D. Hypophosphatasia. Am J Med. 1957;22:730–746.
2. Gurenlian JR. Hypophosphatasia. Access. 2001;15:38-41.
3. Balasubramaniam S, Bowling F, Carpenter K, et al. Perinatal hypophosphatasia presenting as neonatal epileptic encephalopathy with abnormal neurotransmitter metabolism secondary to reduced co-factor pyridoxal-5'-phosphate availability. J Inherit Metab Dis. 2010;33(3):S25-33.
4. Jenny C. Evaluating infants and young children with multiple fractures. Pediatrics. 2006;118(3):1299-303.
5. Girschick HJ, Mornet E, Beer M, et al. Chronic multifocal non-bacterial osteomyelitis in hypophosphatasia mimicking malignancy. BMC Pediatr. 2007;7:3.
6. Whyte MP. Hypophosphatasia and the role of alkaline phosphatase in skeletal mineralization. Endocr Rev. 1994;15:439–61.
7. Krohn-Grimberghe B, Ludwig B, Furkert D. Rathbun syndrome (hypophosphatasia). Clinical aspects: dwarfism and Bechterew symptoms. Z Rheumatol. 1991;50(6):387-91.