CHAPTER 1
Symptoms and Diagnosis
Symptoms and Diagnosis of Rickets
Rickets is a disease where the growth of new bone is impaired. Most commonly, rickets is associated with defects in the metabolism of vitamin D (Figure 1.1), and for this reason most common types of rickets are called vitamin Dâdependent rickets (VDDR). VDDR is thought to impact approximately 50 percent of the population worldwide. Vitamin D can be made by our bodies, but only when we have been exposed to sunlight. Early reports of rickets correlate to the industrial revolution where pollution restricted access to sunlight, and for this reason rickets is a candidate disease for one of the first to be caused by environmental pollution. When VDDR is thought to result primarily from deficiency of vitamin D in the diet (rather than a problem with using the vitamin D that is in the body), it is called nutritional rickets (NR). While NR is a serious disease, it is preventable with appropriate diet changes. Currently, reports suggest that the global incidence of rickets is rising, particularly in dark skinned immigrant populations as compared to native populations, though the prevalence of the disease worldwide is not well recorded.
Rickets is characterized by symptoms of defective bone growth. Both calcium and phosphorous are important minerals found in bone and are responsible for the bone stiffness. Absorption of these minerals depends upon vitamin D, so low levels of vitamin D can lead to osteomalacia, or âsofteningâ of the bone. Because most bone growth occurs during childhood, rickets frequently is first observed during infancy or childhood. General symptoms include pain or tenderness in the bone; tendency to fracture bones; and deformities in areas such as wrists, ribs, knees, or elbows. Rickets can also cause curvature of the legs because the bones are too weak to bear weight, as well as large forehead, abnormally shaped ribs, abnormally curved spine, large abdomen, stunted growth, and teeth abnormalities. In rare cases of VDDR, hair loss can also occur; at times, to the extent that the patient has no body hair at all. Calcium and phosphorous can also be important for neuromuscular function too, so varied symptoms may include defects in muscle function, leading to muscle weakness, at times accompanied by seizures.
Figure 1.1 The chemical structure of vitamin D3
Source: By Sbrools [GFDL (http://www.gnu.org/copyleft/fdl.html), CC-BY-SA-3.0 (http://creativecommons.org/licenses/by-sa/3.0/), or CC BY-SA 2.5 (https://creativecommons.org/licenses/by-sa/2.5)], modified from Wikimedia Commons. J. Org. Chem. (1976) 41, 3476â8.
Rickets can also cause an increase in the amount of parathyroid hormone (PTH), which plays a role in maintaining calcium levels in the body. Changes in PTH can lead to a condition called secondary parahyperthryoidism, which causes the parathyroid glands to become larger than normal. Usually the parathyroid are four small glands, each about the size of a grain of rice, located in the neck. Parathyroid glands control calcium levels in the body by several mechanisms. If blood calcium levels drop, parathyroid glands release PTH into the body. PTH stimulates the release of calcium by regulating the breakdown of bone and increased absorption of calcium in the intestines. PTH also lowers the excretion of calcium in urine by altering kidney function. In this sense, PTH helps maintain the proper balance of calcium available in the body.
If symptoms of rickets are noted, both x-rays of bone structure and blood tests can be used to diagnose the patient. Blood tests are used to detect the amount of the vitamin D, specifically a modified version of vitamin D called 25-hydroxyvitamin D (25OHD). The 25OHD form of vitamin D is freely circulating in the blood stream and is thought to be a good indicator of vitamin D levels for diagnostic tests that can give an early indication of rickets. Specifically, deficiency would be a serum 25OHD concentration less than 12 ng/mL (or 30 nmol/L), and insufficiency would be 12 to 20 ng/mL (30 to 50 nmol/L). The U.S. Institute of Medicine has recently recommended that an individual also be described as being vitamin D insufficient if 25OHD levels fall between 21 and 29 ng/mL. The blood test for 25OHD can also be used to screen for rickets in those cases where children have other bone diseases or are on medications that might interfere with vitamin D production or absorption. The diagnosis of rickets can also include x-rays to detect atypical bone formation and areas of calcium or bone density loss. Although the method is rarely used, bone biopsies can confirm a rickets diagnosis. Phosphate levels are also influenced by vitamin D, so low phosphate levels, hypophosphatemia, can occur in rickets patients. Vitamin D resistant forms of hypophosphatemic rickets can occur, where phosphate levels are too low but for reasons other than vitamin D metabolism.
Other conditions can be associated with healthy levels of vitamin D in the body. Since vitamin D is a fat-soluble vitamin that acts as a steroid hormone, it potentially can influence physiology of many cell types and tissues. Correlations between healthy vitamin D levels and varying health conditions have been identified including anti-inflammatory defects and reduction of colon cancer risk. One study found that patients with lower vitamin D levels were at 60 percent higher risk of heart disease. The third National Health and Nutrition Examination Survey (NHANES-III) found that high blood pressure was also associated with lower vitamin D levels. Increased vitamin D intake is associated with reduced diabetes progression, and in some populations vitamin D intake is correlated with reduction in symptoms of depression. Other nonskeletal diseases associated with vitamin D include polycystic ovary syndrome, thyroid disease, and new-onset Graves disease. A person with rickets may or may not also have these diseases.
Symptoms and Diagnosis of Scurvy
Scurvy is a serious health concern that results from a nutritional deficiency of vitamin C, also known by its chemical name ascorbic acid (Figure 1.2). Scurvy was originally described by Dr. James Lind in 1753 as treatable with citrus fruits, and scurvy was likely the cause of recorded disease as early as the 1500s. Although scurvyâs significance is mostly historical, some resurgence of scurvy can be observed in areas of the world where nutritional access is restricted, or dietary habits do not include sources of ascorbic acid. The Centers for Disease Control and Prevention (CDC) published a study in 2009 finding that 10 to 17 percent of low-income people in the United States suffer from scurvy-level vitamin C deficiency. Scurvy can occur at any age, to any population of individuals with nutritional deficiencies.
The initial symptoms of scurvy can be subtle, making diagnosis at early stages of disease progression more difficult. Initially symptoms may include general weakness, fatigue, and aching limbs. As the disease progresses, the symptoms can include anemia, myalgia (muscle pain), bone pain, easy bruising, swelling, petechiae (skin bleeding), perifollicular hemorrhages (bleeding around the edges of hair follicles), corkscrew hairs, gum disease, poor wound healing, mood changes, and depression. More advanced symptoms include the accumulation of fluids in body tissues (edema), excess levels of the pigment bilirubin (jaundice), bursting of blood cells, (hemolysis), acute spontaneous bleeding, neuropathy (nerve dysfunction), fever, convulsions, and eventually death.
Figure 1.2 Chemical structure of ascorbic acid
Source: By Ben Mills [Public domain], from Wikimedia Commons. https://upload.wikimedia.org/wikipedia/commons/c/ca/Ascorbic-acid-from-xtal-1997-3D-balls.png
Early symptoms of scurvy can be observed in a patient after approximately 8 to 12 weeks of insufficient vitamin C intake, when the bodyâs reserves of vitamin C drop from the standard total body content of 1,500 mg to the pathological threshold of 350 mg. Symptoms will progress as vitamin C levels continue to drop in the patient. This drop in vitamin C levels can be associated with intake below 60 mg of vitamin C per day. Diagnosis usually occurs with physical examination and the determination that the patient has a history of insufficient vitamin C intake. Broad symptoms consistent with the breakdown of blood vessel function, such as hematologic abnormalities, ulcerative gum disease (gingivitis), or blood clotting in deep veins (deep vein thrombosis) can be consistent with scurvy. Since the disease can impact many different organ systems, diagnosis is complicated because it can be confused with other disorders. Despite similarities with other causative disorders, only scurvy can be resolved by increasing dietary consumption of vitamin C.
Symptoms and Diagn...