6 Low Alkaline Phosphatase Causes and Symptoms (Doctor Explains)

Low alkaline phosphatase can be asymptomatic or have symptoms depending on the cause and its severity.

Common symptoms of low alkaline phosphatase include poor bone health, easy fractures, bone pain, symptoms of zinc or magnesium deficiency, etc.

1. Hypophosphatasia:

Hypophosphatasia is a rare genetic disease resulting from a gene mutation responsible for the most common type of alkaline phosphatase (Tissue nonspecific alkaline phosphatase or TNSALP) (reference).

As a result of this genetic disorder, the activity and levels of alkaline phosphatase become persistently low.

The deficient enzyme (TNSALP) is present normal in:

• Bones.
• Developing teeth.
• The kidneys, lungs, and liver are affected to a lesser extent.

The low alkaline phosphatase results in defective bone and teeth development. The disease is rare; severe forms affect one in every 100,000 people.

Symptoms of low alkaline phosphatase due to hypophosphatasia:

• Chronic joint pain, bone pain.
• Muscle pain
• Pathological fractures (easy fractures after minimal trauma such as falling on the ground).
• Delayed fracture healing or non-union of the fractures.
• In children, poor dentition and premature loss of teeth.
• Loss of fully rooted teeth in children and adults (recurrent).
• Calcium deposition in the joints (chondrocalcinosis) (painful & limited joint movement).
• Calcium deposition in the kidney tissues and tubules (nephrocalcinosis) (kidney pain).
• In severe cases, seizures may occur.

The table below summarizes the skeletal (bone) and extra-skeletal symptoms of low alkaline phosphatase due to hypophosphatasia (reference).

The severity of the disease is variable. And it may present at any age according to its severity (reference):

• At birth (perinatal): it is often very severe and leads to the death of the newborn.
• Infancy: early rickets (at 6th month of age). About 50% of infants presenting with hypophosphatasia die during infancy.
• Childhood: present as premature loss of deciduous teeth and delayed walking. The deficiency is milder, and the symptoms often improve spontaneously after puberty but may occur later in life.
• Adulthood presentation: It presents with poor fracture healing, easy fractures, bone pain, etc.

2. Zinc deficiency:

Approximately 17% of people worldwide risk inadequate zinc intake (reference).

Zinc deficiency is one of the common causes of low alkaline phosphatase levels in adults and children.

One study found that 47.6% of patients with low alkaline phosphatase are deficient in zinc (reference)

Causes (reference):

• Nutrition deficiency: insufficient intake or excess phytates (in whole grains, legumes, seeds, and soy products) or oxalates (in spinach, nuts, tea, and okra).
  – Phytates and oxalates decrease zinc absorption.
• Severe chronic illnesses include chronic Gut disease, diabetes, sickle cell disease, kidney disease, etc.
• Excess alcohol drinking.
• Chronic infections.
  

   

• Aging.
  

   

• Some medications: Penicillamine, some antibiotics, evaporates, etc.
• Excess loss as with burns, hemodialysis, diuretics, and hemolytic anemias.
• Inherited zinc deficiency (Acrodermatitis enteropathica).

Symptoms of low alkaline phosphatase due to zinc deficiency.

• Diarrhea.
• Skin symptoms include rash, dermatitis, and cheilitis (inflamed, cracked lips).
• Delayed wound healing.
• Recurrent infections such as diarrhea, pneumonia, etc.
• Poor bone health (decreased bone density) and easy fractures.
• Chronic loss since childhood may lead to growth failure and hypogonadism.

3. Magnesium deficiency.

One study found that more than one-half (52.4%) of the patients with low alkaline phosphatase have a magnesium deficiency.

Causes of magnesium deficiency (reference)

• Poor diet (especially in older ages).
• Diabetes mellitus.
• Persistent diarrhea or vomiting for weeks or months.
• Chronic digestive diseases such as Crohn’s disease.
• Some medications include diuretics, proton pump inhibitors (such as omeprazole and esomeprazole), and some antibiotics.
• Kidney diseases.
• Diuretics (medications that increase urine excretion).
• Excess alcohol intake.
• In critically ill patients.
• Gastric bypass surgery.
• Inherited disorders such as familial hypomagnesemia.

Symptoms of low alkaline phosphatase due to low magnesium.

• Hand tremors.
• Abnormal muscle spasms (tetany).
• In severe cases, seizures may occur.
• Poor concentration, apathy, headaches.
• Irregular or rapid heartbeat (arrhythmias).
• Chest pain (heartattacks).
• Profound loss may lead to loss of consciousness (coma).
• Mild cases may present with asymptomatic low alkaline phosphatase.

4. Hypothyroidism.

Diseases that lead to an underactive thyroid gland may cause low alkaline phosphatase levels.

Hypothyroidism is one of the common diseases (particularly in females). Studies estimate that one in every 20 persons (5%) has an underactive thyroid.

However, low alkaline phosphatase is not present in every patient with hypothyroidism. The low alkaline phosphatase is present in a minority of those patients.

Symptoms of low alkaline phosphatase due to hypothyroidism:

• Generalized fatigue, depression, and low energy.
• Increased sensitivity to cold.
• Puffy, apathetic face.
• Gut symptoms such as chronic constipation.
• Horses of voice.
• Slow heartbeats.
• Weight gain.
• Thick, dry skin.
• Impaired memory.
• Enlarged thyroid gland.

Learn more.

5. Anemia (leads to low alkaline phosphatase).

Severe anemia is often associated with low alkaline phosphatase levels. Also, a specific type of anemia  (pernicious anemia) is more frequently associated with low alkaline phosphatase levels.

Anemia-related alkaline phosphatase causes:

• Pernicious anemia.
• Aplastic anemia (due to bone marrow failure to produce red blood cells).
• Severe hemolytic anemia.
• Celiac disease-related iron deficiency anemia.

• Any other forms of severe anemia.

Symptoms of anemia include:

• Easy fatigue.
• Chronic headache, dizziness, and lightheadedness.
• Shortness of breath on exertion.
• Fast heartbeats (especially with exertion).
• Pale face, lips, and tongue.
• Severe cases may present with extreme tiredness, shortness of breath, and vertigo.
• Hemolytic anemias present with jaundice (yellowish skin and eye whites.

6. Malnutrition.

Malnutrition with low or absent protein in the diet is a common cause of low alkaline phosphatase levels.

Common causes of malnutrition include:

• Severe or long-term health conditions include chronic diarrhea, vomiting, Crohn’s disease, etc.
• Eating disorders such as Anorexia Nervosa.
• Inability to take oral diet (patients with major abdominal, cardiac, or pulmonary surgery).
• Dementia.
• Mental health diseases such as depression, schizophrenia, etc.

Symptoms of malnutrition leading to low alkaline phosphatase:

• Progressive weight loss.
• Lack of appetite.
• Persistent fatigue, weakness.
• Poor skin health.
• Recurrent infections and poor wound healing.
• Poor concentration.
• Feeling cold most of the time.
• Mood changes (depression).

7. Other symptoms of low alkaline phosphatase:

• Wilson’s disease is a rare liver disease due to copper overload. Patients with Wilson’s disease have liver symptoms (jaundice, liver pain, swollen limbs, and belly) and neurological symptoms such as depression, psychosis, tremors, etc.

• Vitamin C deficiency leads to low alkaline phosphatase levels and presents skin bruising, rashes, recurrent infections, poor wound healing, internal bleeding, etc.
• Many medications such as oral contraceptives, cinacalcet, and others cause low alkaline phosphatase levels. Therefore, always remember and report any recent or chronic use of medications to your doctor. 

MORE: Drugs Causing Low & High Alkaline Phosphatase (Chemo, Azathioprine, Thyroid hormone, Tylenol, Metformin, & more).