Work participation in adults with rare genetic diseases - a scoping ...
What Is Hypocalcemia?
Hypocalcemia is when you have too little calcium in your blood. Calcium is essential for your body to function normally. Your hormones control your blood calcium levels.
It can be challenging to know if you have hypocalcemia, as usually it is only discovered through medical tests. Nonetheless, it is essential to treat due to the health problems it can cause.
Hypocalcemia can be caused by certain genetic factors, or due to other deficiencies or conditions.
Usually, hypocalcemia happens when large amounts of calcium are put out when you urinate, or too little calcium enters your blood from your bones. This could be caused by certain genetic factors, vitamin deficiencies, or other conditions.
Some of the reasons either these things can happen include:
Some of the symptoms of hypocalcemia include:
Often, by simply treating hypocalcemia, these symptoms will immediately go away. However, hypocalcemia is usually caused by another condition, so you might experience additional symptoms. In that case, you will need to treat the first condition to treat your hypocalcemia.
The way to find out whether or not you have hypocalcemia is by taking a blood test. This test will be able to find out whether or not you have hypocalcemia. It can also help tell you whether or not it is caused by your kidneys or parathyroid.
If your blood test comes with a blood calcium level of fewer than 8.8 milligrams per decilitre (Mg/dL), that means that you have hypocalcemia. Sometimes you might need further testing to fully understand what is causing your hypocalcemia.
Some of the additional tests could be an ultrasound of your kidneys or genetic testing. An ultrasound is when high-frequency sound waves make a picture of the inside of your body. This allows a doctor to see your organs and other body systems to see any possible problems or abnormalities. However, many different conditions can cause hypocalcemia, so it depends on your unique medical situation.
If you simply just have hypocalcemia, usually vitamin C or vitamin D supplementation is all you need to treat it and take away any symptoms. Usually, if symptoms of hypocalcemia spontaneously happen, your provider will give you intravenous (IV) supplementation.
If your hypercalcemia is due to hyperparathyroidism, your provider might give you a synthetic version of HTP.
After getting diagnosed with hypocalcemia, you will need to get regular testing after being treated. This will ensure your safety and make sure that your blood calcium levels do not get too low ever again. This is especially true for children.
Southwest Florida Geneticist Discovers Chromosome Disorder
Genetic disorders are caused by an abnormality or mutation in one or more genes. Down's syndrome is one of the better-known examples, but more are being discovered all the time. A geneticist with Florida Cancer Specialists & Research Institute knows—she discovered one.
In 1988, Dr. Katy Phelan was introduced to a little boy who presented as a medical mystery. A genetic sleuth, she was part of a team who dove into his DNA.
"And we found that he had a deletion, a small piece of chromosome 22 that was missing, and we hadn't seen that literature before," Phelan said.
After publishing her findings, several families came forward, hoping this would explain similar traits they saw in their own children. Carla D'Imperio and her husband noticed something unusual about Matthew, their 8-year-old middle child. "He was very unique from the start, and there were some little things right off the bat that were different."
D'Imperio family. CREDIT: WINK NewsOutward signs included: poor muscle tone, droopy and puffy eyes, along with long eyelashes. There are also associated cognitive and speech impairments, in addition to medical conditions including epilepsy and autism.
The degree of traits depends on the length of deletion in chromosome 22. Dr. Phelan knows better than anyone how this condition manifests.
"I think I have talked to more individuals with this syndrome than anyone else in the world," she said.
It is why impacted families chose to name the condition after her, calling it Phelan-McDermid syndrome.
Giving it an official name and diagnosis helps families understand and process the syndrome.
"We had a reason for some of the things that have been going on with [Matthew]," Carla D'Imperio said. "We also found great support in knowing that we had a community where there were people working on answers."
They are still learning things about Matthew. Slow to walk and non-verbal, the family said he is happy, enjoys his siblings and watching videos on his digital devices. He also has a wicked sense of humor. "There's a little bit of a mischief element to Matthew," said D'Imperio, "where he kind of likes to see people's reactions with different things and see what he can get away with."
Dr. Phelan, who helped connect and establish the Phelan-McDermid Foundation, tells WINK News there is research being done to find treatments for some of the related medical conditions.
"Some of it is repurposing already FDA-approved therapy, so some therapy that might be used for diabetes might be able to be repurposed for some issue in these children," Phelan said.
There is no way to correct this mutated gene, but the families like to say they are "Phelan lucky."
PTEN-RELATED DISORDERS
PTEN-RELATED DISORDERSComprehensive Test - Test 1
DESCRIPTION
Mendelian Inheritance in Man number: *601728 (PTEN gene); 158350 (Cowden syndrome, CS); 153480(Bannayan-Riley-Ruvalcaba syndrome, BRRS); 176920 (Proteus syndrome, PS); 605309 (Macrocephaly/Autism syndrome)
Click here forGene Reviews Clinical Summary.
PTEN hamartoma tumor syndrome (PHTS) includes Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome (BRRS), Proteus syndrome (PS), and Proteus-like syndrome. This group of disorders shares significant clinical overlap [Eng, 2003]. Each of these disorders is inherited in an autosomal dominant manner, and de novo mutations are common.
1. CS is a multiple hamartoma syndrome with a high risk of benign and malignant tumors of the thyroid (10%), breast (25-50%), and endometrium (10%). Most patients usually have macrocephaly and pathognomonic mucocutaneous lesions, including trichilemmomas, papillomatous papules, and acaral and plantar keratoses. Other tumors include harmartomatous polyps of the GI tract, fibrocystic disease of the breast, fibromas, cerebellar dysplastic gangliocytoma (Lhermitte-Duclos disease), skin cancers, renal cell carcinomas, uterine leiomyoma, and brain tumors as well as vascular malformations affecting any organ.
2. BRRS is characterized by macrocephaly, intestinal polyposis, lipomas, and pigmented macules of the glans penis. Other common features include developmental delay, mental retardation, hamartomatous polyps of the GI tract, a myopathic process in proximal muscles, joint hyperextensibility, pectus excavatum, and scoliosis. Individuals with BRRS who have PTEN gene mutations are thought to have the same cancer risks as individuals with CS.
3. PS is a complex, highly variable disorder consisting variably of disproportionate, asymmetric overgrowth of body parts; cerebriform connective tissue nevi; epidermal nevi; vascular malformations of the capillary, venous, and lymphatic types; dysregulated adipose tissue; and hyperostoses[Cohen, 2005]. Unusual tumor types have been observed, such as cystadenoma of the ovary, various types of testicular tumors, central nervous system tumors, and parotid monomporphoic adenomas. Somatic mosaicism, lethal in the nonmosaic state, is the present hypothesis for PS.
4. Proteus-like syndrome is undefined but refers to individuals with significant clinical features of PS who do not meet the diagnostic criteria for PS.
5. Macrocephaly/Autism Syndrome is one of PTEN-related disorders. Autism is associated with macrocephaly in approximately 20% of cases. Several studies have shown that PTEN mutations can be found in a subset of individuals who present with autism and macrocephaly, with or without the presence of other features of PTEN-related tumor syndrome [Butler et al. 2005, Buxbaum et al. 2007, Goffin et al. 2001, Herman et al. 2007]. Therefore, PTEN sequence analysis may be considered as additional testing when other genetic causes of autism have been ruled out through the autism panel.
INDICATIONS FOR DIRECT TESTING
TESTING METHODOLOGY
From a fresh EDTA blood sample, DNA is extracted and used as the starting material for direct sequencing of the entire coding region.MLPA analysis to detect copy number changes is performed. Mutations screened for include truncating mutations (nonsense, frameshift, splicing mutations), missense mutations, multi-exon deletions and total gene deletions.
Test sensitivity varies depending on the clinical diagnosis. The sequencing approach used by MGL will identify >99% of intragenic minor lesion mutations in the PTEN gene. Partial or whole gene deletions/duplications can be detected by MLPA copy number analysis.
SPECIMEN REQUIREMENTS
We require 10 milliliters of whole blood. Blood samples must be collected in EDTA (purple topped) tubes. For pediatric patients or those for whom venipuncture is very difficult, please send a minimum of 3 ml in EDTA. Please note that if you order PTEN gene testing in addition to Fragile X testing for pediatric patients, we require a minimum of 5 milliliters of whole blood.
TRANSPORT
If specimen is from clinics within UAB or Kirklin Clinic, please call 934-5562 for pick-up. If specimens are being sent from some other location, please ship via UPS or Federal Express.
IMPORTANT!
Blood specimens must be kept at room temperature and received within 60 hours of collection.
1. DO NOT SHIP ON ICE.2. Be sure that the shipping air bill is marked "Priority", either Domestic or International.3. Specimens must be packaged to prevent breakage and absorbent material must be included in the package to absorb liquids in the event that breakage occurs. Also, the package must be shipped in double watertight containers (e.G. A specimen pouch + the shipping companies Diagnostic Envelope). You can use our collection kits, which we will send to physicians directly upon request.4. Please contact us (Emailmedgenomics@uabmc.Edu, Phone – 205-934-5562) prior to sample shipment and provide us with the date of shipment and the tracking number of the package, so that we can better ensure receipt of the samples within the 60-hour window. Please include the form for customs. This is especially important for samples sent from outside the US.
TURN AROUND TIME
25 working days
REQUIRED FORMS
PTEN Test Requisition including the phenotypic data form.
Form for customs (International shipment)
Note: Requests for Molecular Genetic testing for PTEN will not be accepted for the following reasons:
No label (patient's full name and date of collection) on the specimens
For more information, test requisition forms, or sample collection and mailing kits, please call: 205-934-5562.
REFERENCES
Barker K, Martinez A, Wang R, Bevan S, Murday V, Shipley J, Houlston R, Harper J (2001) PTEN mutations are uncommon in Proteus syndrome J Med Genet. 38: 480-1 (PubMed)
Buxbaum JD, Cai G, Chaste P, Nygren G, Goldsmith J, Reiehert J, et al. (2007) Mutation Screening of the PTEN gene in patients with autism spectrum disorders and macrocephaly. Am J Med Genet. 144B:484-91. (PubMed)
Butler MG, Dasouki MJ, Zhou XP, Talebizadeh X, Brown M, Takahashi TN, et al. (2005) Subset of individuals with autism spectrum disorders and extreme macrocephaly associated with germline PTEN tumor suppressor gene mutations. J Med Genet. 42:318-21. (PubMed)
Cohen MM Jr. (2005) Proteus syndrome: An update. Am J Med Genet. 137C:38-52. (PubMed)
Eng C. (2003) PTEN: one gene, many syndromes. Hum Mutat. 22(3):183-98. (PubMed)
Eng C, Thiele H, Zhou XP, Gorlin RJ, Hennekam RC, Winter RM (2001) PTEN mutations and proteus syndrome. Lancet. 358: 210-1 (PubMed)
Goffin A, Hoefsloot LH, Bosgoed E, Swillen A, Fryns JP. (2001) PTEN Mutation in a Family With Cowden Syndrome and Autism. Am J Med Genet 105(6):521-24. (PubMed)
Herman GE, Butter E, Enrile B, Matthew P, Prior TW, Sommer A. (2007) Increasing knowledge of PTEN germline mutations: two additional patients with autism and macrocephaly. Am J Med Genet. 143A:589-93. (PubMed)
Pezzolesi MG, Zbuk KM, Waite KA, Eng C (2007) Comparative genomic and functional analyses reveal a novel cis-acting PTEN regulatory element as a highly conserved functional E-box motif deleted in Cowden syndrome Hum Mol Genet. 16: 1058-71 (PubMed)
Smith JM, Kirk EP, Theodosopoulos G, Marshall GM, Walker J, Rogers M, Field M, Brereton JJ, Marsh DJ (2002) Germline mutation of the tumour suppressor PTEN in Proteus syndrome J Med Genet. 39: 937-40 (PubMed)
Zhou XP, Waite KA, Pilarski R, Hampel H, Fernandez MJ, Bos C, Dasouki M, Feldman GL, Greenberg LA, Ivanovich J, Matloff E, Patterson A, Pierpont ME, Russo D, Nassif NT, Eng C (2003) Germline PTEN promoter mutations and deletions in Cowden/Bannayan-Riley-Ruvalcaba syndrome result in aberrant PTEN protein and dysregulation of the phosphoinositol-3-kinase/Akt pathway. Am J Hum Genet. 73: 404-11 (PubMed)
Zhou XP, Marsh DJ, Hampel H, Mulliken JB, Gimm O, Eng C (2000) Germline and germline mosaic PTEN mutations associated with a Proteus-like syndrome of hemihypertrophy, lower limb asymmetry, arteriovenous malformations and lipomatosis Hum Mol Genet. 9: 765-8 (PubMed)
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