FAQ/Glossary of Terms

Frequently Asked Questions

Get answers to the most frequently asked questions about GACI and ARHR2!  If you don’t see the answer to your question here, you could try navigating via the sitemap at the bottom of the page or using the search option.  If you still have unanswered questions, please email us at info@gaciglobal.org.

There is a lot of variabilities that affect survival odds – the age at diagnosis, the severity of the disease at diagnosis, treatment, etc.  Taking these things into consideration, survival rates for GACI are estimated at around 50%.

With proper medical care and treatment, your child can live a very full and happy life.  They will likely have to take medication daily and have regular follow-up appointments with their medical care team, but this should not stop them from attending school, participating in sports or activities, etc.  You can read more here.

There is currently an enzyme replacement therapy in clinical trials.  We are hopeful that this therapy will be life changing for patients affected by GACI / ARHR2.  You can learn more here.

ARHR2 typically presents in early childhood, but there is no exact age of onset.

Bone pain and bone deformities may be the first externally visible signs of ARHR2.  However, ARHR2 can be diagnosed, before any bone changes occur, by plasma (blood) test.  ARHR2 does not always show up on an X-ray in the way that normal rickets would.  Therefore patients with GACI Type 1 should have routine blood tests to ensure any elevated plasma alkaline phosphatase levels are investigated.

Medication for ARHR2 is required daily for life.

Rickets develops when growing bones fail to mineralize.  There are many different forms of rickets.  Some forms of rickets are caused by nutritional deficits while other forms of rickets are caused by genetic defects.  Researchers have described several forms of genetic hypophosphatemic rickets, which are distinguished by their pattern of inheritance and the gene responsible.  The most common form of the disorder is known as X-linked Hypophosphatemic Rickets (XLH).  It has an x-linked dominant pattern of inheritance.  Autosomal recessive forms of rickets, such as ARHR2, are much rarer, but the main point of difference is the genetic cause of the disease.  They are similar in the fact that both conditions lead to elevated FGF23 levels.  FGF23 is a protein that is responsible for phosphate and vitamin D metabolism.

Please contact us at info@gaciglobal.org.

Depending on their symptoms and what type of complications they are diagnosed with, patients with GACI are usually followed by a team of specialists that may include cardiology, endocrinology, nephrology, orthopedics, audiology, ophthalmology, pulmonology, otolaryngology, physical therapy, dental, and gastroenterology.

There is some clinical evidence that heart transplants can be successful in patients with GACI, without recurrence of calcification.  Heart transplant for individuals with GACI has occurred in at least 4 known cases in the US, Italy, and Spain, with the youngest patient being 4 months old.

For patients with ARHR2, there are some surgical options available if treatment with medication was not started soon enough or did not produce the desired results.  The two surgical options to correct the bone deformities caused by ARHR2 are eight-plate surgery or osteotomy.  Read more here.

In at least one case, surgery was successfully performed to remove the periarticular calcification of a patient with GACI to improve the range of motion and function of the joint.

We have a private Facebook group specifically for families and patients.  Please keep in mind that this group is strictly for families directly impacted by GACI/ARHR2.  It is not a group for extended relatives, friends, etc.  This group exists to provide a place for these families to connect, communicate, commiserate, and support each other.

Pyrophosphate (PPi) is important in controlling calcification and other mineralization in the body.

The ENPP1 gene provides instructions for making a protein that helps to break down a molecule called ATP (adenosine triphosphate) when it is found outside the cell (extracellular). Extracellular ATP is broken down into AMP (adenosine monophosphate) and pyrophosphate. Mutations in the ENPP1 gene result in low levels of pyrophosphate.

The ABCC6 gene provides instructions for making a protein called MRP6 (ABCC6 protein). Mutations in the ABCC6 gene lead to non-functional or absent MRP6 protein. It is thought that the lack of MRP6 protein impedes the release of ATP from cells and as a result, pyrophosphate production is limited.

Glossary of Terms

Below you will find a glossary of terms related to Generalized Arterial Calcification of Infancy and Autosomal Recessive Hypophosphatemic Rickets Type 2.

ABCC6 Deficiencyis an inherited genetic condition caused by mutations in the ABCC6 gene.

ABCC6 gene – ATP-binding cassette sub-family C member 6.

Angioid Streak – small breaks in Bruch’s membrane, an elastic tissue containing membrane of the retina that may become calcified and crack.

ARHR2 – Autosomal Recessive Hypophosphatemic Rickets Type 2

Atherosclerosis – is a condition where the arteries become narrowed and hardened due to a buildup of plaque around the artery wall.

Audiology – the branch of science that studies hearing, balance, and related disorders.

Bisphosphonates – This is a class of drug that prevents the loss of bone density, usually used to treat osteoporosis and similar diseases.  Etidronate, Risedronate, and Pamidronate are examples of bisphosphonates that have shown some success in treating patients with GACI.

Calcific Enthesopathy – a problem with the attachment of tendons, ligaments, or components of a joint onto the bone.

Calcinosis – deposition of calcium in the skin, subcutaneous tissue, muscles, and visceral organs.

Cardiology – the branch of medicine that deals with diseases and abnormalities of the heart.

Cardiomegaly – a medical condition in which the heart is enlarged.

Cardiomyopathy – a disease of the heart muscle that makes it harder for the heart to pump blood to the rest of the body.

Cardiovascular – relating to the circulatory system, which comprises the heart and blood vessels.

Craniosynostosis – the premature fusion of the skull bones.

CT scan – Computed Tomography scan – A CT scan combines a series of X-ray images taken from different angles around your body and uses computer processing to create cross-sectional images (slices) of the bones, blood vessels, and soft tissues inside your body.

Cyanosis – bluish cast to the skin and mucous membranes. Peripheral cyanosis is when there is a bluish discoloration to your hands or feet. It’s usually caused by low oxygen levels in the red blood cells or problems getting oxygenated blood to your body.

DEXA scan – dual-energy x-ray absorptiometry – a scan to measure bone density.  The scan is fast and the dose of radiation used is low.

Echocardiograms – often referred to as an echo is a sonogram of the heart.

Echogenicity – the brightness of the major arteries.

Edema – a medical term for swelling.

Eight-Plate Surgery – a surgical procedure where a plate is attached to one side of the growth plate above or below the knee or sometimes both above and below the knee.  Over time, as the patient grows, this helps to realign the legs.

EKG/ECG’s – Electrocardiogram – a recording/graph of voltage versus time – of the electrical activity of the heart using electrodes placed on the skin.

Endocrinology – the branch of physiology and medicine concerned with endocrine glands and hormones.

ENPP1 Deficiency – is an inherited genetic condition caused by mutations in the ENPP1 gene.

ENPP1 gene – ectonucleotide pyrophosphatase/phosphodiesterase 1

ERT – Enzyme Replacement Therapy

FGF23 – Fibroblast growth factor 23 is a protein that in humans is encoded by the FGF23 gene. It is a member of the fibroblast growth factor (FGF) family which is responsible for phosphate and vitamin D metabolism.

GACI – Generalized Arterial Calcification of Infancy

Hypercalciuria – a condition of elevated calcium in the urine.  Kidneys that put out higher levels of calcium than normal.

Hyperphosphaturia – the presence of excess phosphate in the urine.

Hypertension – high blood pressure.

Hypophosphatemia – low level of phosphate in the blood.

Infraocclusion – This is a condition frequently associated with primary molars, where primary teeth remain in a fixed position, while teeth adjacent to them continue to erupt.

Inorganic Pyrophosphate (PPi) – essential for preventing harmful soft tissue calcification and for regulating normal bone mineralization.

Intima – the inner layer of artery or vein.

Intimal Hyperplasia – the thickening of the innermost layer of the blood vessels.

Lamina– The internal elastic lamina is a layer of elastic tissue that forms the outermost part of the blood vessels.

MRI – Magnetic Resonance Imaging is a scan that uses powerful magnets, radio waves, and a computer to make detailed pictures inside your body.  MRI scans typically take longer, are louder, and do not use x-rays or other radiation.

Mutation – a permanent alteration in the DNA sequence that makes up a gene, such that the sequence differs from what is found in most people.

Nephrocalcinosis – a condition in which calcium levels in the kidneys are increased.

Nephrology – the branch of medicine that deals with the physiology and diseases of the kidneys.

Ophthalmology – the branch of medicine and surgery, which deals with the diagnosis and treatment of eye disorders.

Orthopedics – the branch of medicine dealing with the correction of deformities of bones or muscles.

Osteotomy – a surgical procedure where a bone is cut to change its alignment.

Otolaryngology – the branch of medicine that deals with conditions of the ear, nose, and throat and related structures of the head and neck.

Periarticular – situated or occurring around a joint of the body.

Pericardial Effusion – fluid around the heart.

PGD – preimplantation genetic diagnosis.

Polyhydramnios – excess amniotic fluid.

Pyrophosphate (PPi) – is a chemical that is important for controlling calcification and other mineralization in the body.

Sodium Thiosulfate (STS) – STS is a calcium-chelating agent that is used by patients who have excess calcium in their arteries due to kidney disease.  It has also shown some success in patients with GACI.

Soft-tissue calcification – a process in which tissue becomes hardened by deposition of calcium salts, which normally occurs only in bone and teeth.

Stapedovestibular Ankyloses – immobility of an ear bone.

Stenosis – narrowing of an artery.

Tendinopathy – also known as tendinitis or tendinosis, is a type of tendon disorder that results in pain, swelling, and impaired function.  Can be related to calcium deposits.

Vascular – relating to, affecting, or consisting of a vessel or vessels, especially those which carry blood.