Medical Features

Living with Lowe Syndrome

III. Medical Features, cont'd.

E. Bones and joints

1. Rickets and soft bones. Many children with Lowe syndrome have a history of soft bones or rickets. This condition probably results from a combination of problems. As bones grow and form they need to "ossify" or become solid. Phosphate, along with calcium, vitamin D, and other nutrients and hormones, as well as proper acid-base balance, are needed for proper ossification and bone remolding with growth. Vitamin D is normally converted to its active metabolite, 1,25-dihydroxy vitamin D or calcitriol, in the kidney tubules. Since the kidney tubules are abnormal in Lowe syndrome, some patients may not make enough calcitriol to keep the bones strong and to enhance intestinal absorption of phosphate supplements. In addition, muscle tension on the bones due to exercise and movement is also thought to be necessary to keep the bones strong. When the muscles are weak (hypotonia), they do not perform this function well. Low blood phosphate, acidosis, hypotonia, and other kidney problems in Lowe syndrome all place the boys at risk of developing soft bones, rickets (in the growing child) or osteomalacia (in the adult). Problems associated with these conditions include fractures and scoliosis.

Rickets or osteomalacia can often be improved by giving oral preparations of neutral phosphate in addition to the potassium and bicarbonate preparations mentioned above. A side effect of oral phosphate is loose stools, so the dosage must be started low and carefully monitored. Occasionally, vitamin D metabolite preparations, such as calcitriol or dihydrotachysterol, are needed. Therapy with these medications should be carefully monitored to prevent the complications of kidney stones or calcium deposits in the kidney tissue (see "Nephrocalcinosis" in Kidneys). Since patients with Lowe syndrome may be predisposed to developing kidney calcifications even without vitamin D metabolite therapy, the kidneys should be checked for this condition by ultrasound or x-ray before starting, and at intervals during, any therapy with vitamin D metabolites. Plain vitamin D (parent compound) may not be effective as therapy because it may not be converted by the kidneys to the active metabolite.

All medications and dosages must be individualized for each child by his physician. Blood and urine tests and X-rays are usually ordered periodically. Blood tests may be done to measure calcium, phosphorus, bicarbonate, alkaline phosphatase, vitamin D metabolites, and parathyroid hormone.

Alkaline phosphatase is an enzyme made in bone. When the bone is actively breaking down as in rickets, or when the bone is actively growing and forming new bone as during healing of rickets, the blood level of alkaline phosphatase will be elevated.

The metabolites of vitamin D that are measured are 25-hydroxy vitamin D, which is made in the liver, and 1,25-dihydroxy vitamin D or calcitriol, which is made in the kidney. The 25-hydroxy vitamin D level indicates whether the dietary intake of vitamin D is adequate, while the calcitriol level indicates whether the kidney is making adequate amounts of this substance for bone growth and prevention of rickets.

Parathyroid hormone is a hormone made in a gland in the neck near the thyroid. Parathyroid hormone regulates calcium levels in the body and may be elevated when a patient has rickets or is receiving too much phosphorus supplementation.

Urine tests may be done to measure phosphorus, calcium, albumin, creatinine, and pH and will indicate the severity of the urinary losses of calcium, phosphorus, albumin, and bicarbonate.

Changes for all medications should be made only by the physician since medical problems may develop if the medication doses are too high or too low.

2. Fractures. About half of boys experience bone fractures, which often involve the upper leg when they are learning to walk at about 6 years of age. One-third have more than one fracture, usually involving the arms and/or legs. Some fractures can probably be prevented if careful attention is paid to early diagnosis and treatment of hypophosphatemia, acidosis, and rickets or osteomalacia.

3. Scoliosis. About half of boys develop scoliosis, or curvature of the spine, by adolescence or adulthood. The severity of this condition varies from mild to severe. In severe cases, scoliosis can adversely affect mobility and cause back pain and diminished lung capacity. In some cases, this condition is treated effectively through the use of a brace or cast or surgery.

4. Short stature. Boys with Lowe syndrome are generally of normal length at birth but by one year of age, most have fallen well below the normal range of height (see Figures 2 and 3 below). Growth continues, but at a slower ratethan normal. The average adult height is about 5 feet, 1 inch or 155 cm. The underlying cause of the short stature is unknown. Studies are being done to determine the effectiveness and safety of human growth hormone therapy. Reportedly, several children with Lowe syndrome have been successfully treated with human growth hormone. However, the effectiveness and the benefits of the supplementation must be balanced against the significant expense of the therapy and the potential social and psychological factors.

Figure 2. Growth Chart Ages 0-36 Months
The colored lines represent normal growth patterns for boys ages 0-36 months. The black, dashed line represents the average growth pattern of boys with Lowe syndrome ages 0-3 (based on data from the Lowe Syndrome Comprehensive Survey, 1991).

Figure 3. Growth Chart Ages 3-18 Years
The colored lines represent normal growth patterns for boys ages 3-18 years old. The black, dashed line represents the average growth pattern of boys with Lowe syndrome ages 3-18 (based on data from the Lowe Syndrome Comprehensive Survey, 1991).

5. Joint swelling and arthritis. Other orthopedic problems associated with Lowe syndrome include joint swelling, arthritis, and benign growths called fibromas (especially on the feet and hands). These problems are particularly prevalent in the teenage and adult years. In some cases these problems can be quite severe and debilitating. The underlying cause is unknown and there is no effective therapy except treatment for pain.

6. Teeth. Many individuals with Lowe syndrome require extensive dental care. A high palate, small mouth, rickets, and other bone and metabolic factors often result in crowding, poor alignment, the susceptibility to decay, and delayed shedding of primary teeth. Many children require teeth extraction. A few have successfully worn braces. Dental cysts (sometimes called "eruption cysts") appear to be quite common with teething but usually resolve after permanent teeth are in. Regular dental care should be started when the first baby teeth have erupted.