Galactosemia

Galactosemia is a rare genetic metabolic disorder which affects an individual's ability to properly metabolize the sugar galactose.

Goppert first described the disease in 1917, with its cause as a defect in galactose metabolism being identified by a group led by Herman Kalckar in 1956.

Its incidence is about 1 per 47,000 births (classic type). It is much rarer in Japan and much more common in Italy, specifically the traveler region.

Cause

Lactose in food (such as dairy products) is broken down by the body into glucose and galactose.In individuals with galactosemia, the enzymes needed for further metabolism of galactose are severely diminished or missing entirely, leading to toxic levels of galactose to build up in the blood, resulting in hepatomegaly (an enlarged liver), renal failure, cataracts, and brain damage. Without treatment, mortality in infants with galactosemia is about 75%.

Types

Galactose is converted into glucose by the action of three enzymes, known as the Leloir pathway. Accordingly, there are 3 known types of Galactosemia; type 1, 2 and 3:

Type	Diseases Database	OMIM	Gene	Locus	Enzyme	Name
Type 1	5056	230400	GALT	9p13	galactose-1-phosphate uridyl transferase	classic galactosemia
Type 2	29829	230200	GALK1	17q24	galactokinase	galactokinase deficiency
Type 3	29842	230350	GALE	1p36-p35	UDP galactose epimerase	galactose epimerase deficiency, UDP-Galactose-4-epimerase deficiency

The order of these three types is not the same as the order that the enzymes are encountered by galactose on its metabolic path (which is closer to GALK, GALT, and then GALE, though many variations can occur.)

Treatment

The only treatment for classic galactosemia is eliminating lactose and galactose from the diet. Even with an early diagnosis and a restricted diet, however, some individuals with galactosemia experience long-term complications such as speech difficulties, learning disabilities, neurological impairment (e.g. tremors, etc), and in girls, ovarian failure. These complications are treated if they appear in a manner similar to the way they would be treated in a non-galactosemic. Such complications have not been associated with Duarte galactosemia, and many individuals with Duarte galactosemia do not need to restrict their diet at all. Infants with classic galactosemia cannot be breast-fed due to lactose in human breast milk and are usually fed a soy-based formula.^[3]

Galactosemia is sometimes confused with lactose intolerance, but galactosemia is a more serious condition. Lactose intolerant individuals have an acquired or inherited shortage of the enzyme lactase, and experience abdominal pains after ingesting dairy products, but no long-term effects. In contrast, a galactosemic individual who consumes galactose can cause permanent damage to their bodies.

Long term complication of galactosemia includes:

• Speech deficits
• Ataxia
• Dysmetria
• Diminished bone density
• Premature ovarian failure
• Cataract

For a thorough scientific overview of galactosemia, one can consult chapter 72 of OMMBID. For more online resources and references, see inborn error of metabolism.

Osteoporosis

Osteoporosis is a reduction in bone mass per unit volume. Osteoporosis leads to literally abnormally porous bone that is more compressible like a sponge, than dense like a brick. This disorder of the skeleton weakens the bone causing an increase in the risk for breaking bones (bone fracture). The fracture can be either in the form of cracking (as in a hip fracture), or collapsing (as in a compression fracture of the vertebra of the spine). The spine, hips, and wrists are common areas of bone fractures from osteoporosis, although osteoporosis-related fractures can also occur in almost any skeletal bone.

A = NORMAL BONE
B = OSTEOPOROTIC BONE

OSTEOPOROSIS

Primary:
Type I Postmenopausal osteoporosis (50 to 75 years) due to decrease oestrogen. Affects spine and wrist

Type 2 Seniele osteoporosis (70years and above). Affects hip and spine

Induced by : smoking, alcohol, less intake of calcium, white ras, less activity,thin

Secondary:
caused by: hyperthyroid,hyperparathyroid,
corticosteroid, multiple myeloma, malnutrition,
hypogonadism, chronic renal failure,
medications

Symptoms

Osteoporosis is a silent disease, it can be present without any symptoms for decades, because osteoporosis doesn't cause symptoms unless bone fractures.

The symptoms of generalizes of oteoporosis include chronic intermitten back pain (which is probably related to repeated microscopic fractures)


Risk factors

Radiographic Diagnosis
The radiographic features include a generelized rarefaction of all bones (but most marked in cancellous bone), thin cortices, and evidence of deformity, particularly in vertebral bodies.

A relatively recent development is bone densiometry to quantitate accurately the bone mineral density of a given patient. The current method of choice is dual energy X-ray absorptiometry (DEXA)

Dual energy X-ray absorptiometry (DXA, formerly DEXA) is considered the gold standard for the diagnosis of osteoporosis. Osteoporosis is diagnosed when the bone mineral density is less than or equal to 2.5 standard deviations below that of a young adult reference population. This is translated as a T-score. The World Health Organization has established the following diagnostic guidelines:

• T-score -1.0 or greater is "normal"
• T-score between -1.0 and -2.5 is "low bone mass" (or "osteopenia")
• T-score -2.5 or below is osteoporosis

When there has also been an osteoporotic fracture (also termed "low trauma-fracture" or "fragility fracture"), defined as one that occurs as a result of a fall from a standing height, the term "severe or established" osteoporosis is used.

The International Society for Clinical Densitometry takes the position that a diagnosis of osteoporosis in men under 50 years of age should not be made on the basis of densitometric criteria alone. It also states that for pre-menopausal women, Z-scores (comparison with age group rather than peak bone mass) rather than T-scores should be used, and that the diagnosis of osteoporosis in such women also should not be made on the basis of densitometric criteria alone.

Treatment

1. Medication

Bisphosphonates are the main pharmacological measures for treatment. However, newer drugs have appeared in the 1990s, such as teriparatide and strontium ranelate.

Estrogen replacement therapy remains a good treatment for prevention of osteoporosis but, at this time, is not recommended unless there are other indications for its use as well. There is uncertainty and controversy about whether estrogen should be recommended in women in the first decade after the menopause.

Some SERMs such as raloxifene (Evista), act on the bone by slowing bone resorption by the osteoclasts. Others, such as Femarelle (DT56a), achieve a significant effect by stimulating osteoblast activity thus inducing new bone formation.

2. Nutrition

Calcium, Vitamin D

3. Exercise