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Rathbun Syndrome

HPP

The Rathbun syndrome, also known as hypophosphatasia, is a congenital, autosomal recessive disease caused by defective encoding of tissue-nonspecific alkaline phosphatase leading to peripheral (serum and tissue) deficiency of this enzyme. The illness has several degrees of severity, causing symptoms at various ages. The most serious form manifests during the newborn period and leads to death.


Presentation

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].

Respiratory Distress
  • 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.[symptoma.com]
Poor Feeding
  • 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]
  • Infantile hypophosphatasia [ edit ] Infantile hypophosphatasia presents in the first 6 months of life, with the onset of poor feeding and inadequate weight gain. Clinical manifestations of rickets often appear at this time.[en.wikipedia.org]
Epistaxis
  • Battle\'s sign may be the only outward sign of basilar skull fracture, or it may be accompanied by periorbital ecchymosis (raccoon eyes), conjunctival hemorrhage, nystagmus, ocular deviation, epistaxis, anosmia, a bulging tympanic membrane (from CSF or[checkorphan.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]
Papilledema
  • 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.[symptoma.com]

Workup

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.

Treatment

  • Apply the latest treatments, rehabilitation protocols, and expertise of leading surgeons and therapists to help your patients regain maximum movement after traumatic injuries or to improve limited functionality caused by chronic or acquired conditions[books.google.de]
  • There is no treatment, and prognosis depends on the age of onset. Severe hypophosphatasia may be fatal in infancy.[britannica.com]
  • [ edit ] As of October 2015, asfotase alfa (Strensiq) has been approved by the FDA for the treatment of hypophosphatasia.[en.wikipedia.org]
  • Treatment - Sommer Rathbun Battles syndrome Not supplied. Resources - Sommer Rathbun Battles syndrome[checkorphan.org]
  • Whyte MP, Greenber CR, Ozone K, Riese R, Moseley S, Melian A, Thompson D, Hofmann C: Asfotase Alfa Treatment Improves Survival For Preinatal And Infantile Hypophosphatasia. Journal of Clinical Endocrinology and metabolism 2016;101: 334-42.[rarediseases.org]

Prognosis

  • There is no treatment, and prognosis depends on the age of onset. Severe hypophosphatasia may be fatal in infancy.[britannica.com]
  • 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]
  • Prognosis Patients with significant venous reflux are at high risk for progression to chronic venous ulcers that can be very difficult to treat effectively. With appropriate treatment, the vast majority of patients have a good outcome.[emedicine.medscape.com]

Etiology

  • Mundle Springer Science & Business Media , 06.12.2012 - 280 Seiten 0 Rezensionen 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[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]
  • Hence, there is an urgent need for increasing physician awareness about risk factors, etiology and the management of this unique and relatively infrequent disorder.[westjem.com]

Epidemiology

  • 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]
  • 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 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]
  • Epidemiology United States Approximately 23% of adults in the United States have varicose veins.[emedicine.medscape.com]
  • Epidemiologi Insidensi OMSK tampaknya tergantung pada ras dan faktor sosioekonomi.[duableg.blogspot.com]
Sex distribution
Age distribution

Pathophysiology

  • Pathophysiology Alkaline phosphatase is present as 4 isomers, each with its own gene locus. Three of these isoforms are tissue specific and are known as germ cell, placental, and intestinal alkaline phosphatase.[emedicine.medscape.com]
  • In all probability, the intrinsic and the extrinsic theories coexist and explain the pathophysiology of rotator cuff degeneration.[emedicine.medscape.com]
  • At the ACMG Annual Meeting in Tampa, Florida, we talked with Mari Mori, MD, from Duke University Medical Center about the pathophysiology of ...[kinder-surprise-video.ru]
  • Pathophysiology Varicose veins and spider veins are normal veins that have dilated under the influence of increased venous pressure. In healthy veins, one-way valves direct the flow of venous blood upward and inward.[emedicine.medscape.com]

Prevention

  • 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]
  • 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]
  • When the weakened cuff cannot prevent the humeral head from rising under the pull of the deltoid, the residual cuff becomes squeezed between the humeral head and the coracoacromial arch, contributing to further cuff degeneration.[emedicine.medscape.com]
  • Soft Tissues Rheumatic Pain: Recognition, Management and Prevention. Pine J Williams & Wilkins, Maryland. 1996. Pag 89-99. 10.Peinado JM. Peinado JE. Estudio de la vascularización tendinosa del hombro.[sisbib.unmsm.edu.pe]
  • Genetic screening is a good tool to improve health, but what happens if there was another way to prevent a genetic disease for future generation.[123helpme.com]

References

Article

  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.

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Last updated: 2018-06-22 08:42