bubble_chart Overview

Vitamin D deficiency-induced tetany, also known as infantile tetany, is most commonly seen in infancy. It is primarily caused by a lack of vitamin D, leading to low serum calcium levels and increased neuromuscular excitability, resulting in symptoms such as convulsions and tetany. In recent years, the incidence of this condition has been decreasing annually.

bubble_chart Etiology

The etiology is the same as rickets, but the clinical manifestations and changes in blood generation and transformation differ. Although this condition is often accompanied by grade I rickets, the skeletal changes are not severe, with low blood calcium and mostly normal blood phosphorus, while alkaline phosphatase is elevated.

The decrease in serum calcium ions is the direct cause of this condition. Under normal circumstances, diffusible calcium accounts for about 60% of the total calcium. If the total serum calcium drops to 1.75–1.88 mmol/L (7–7.5 mg/dl) or the calcium ion level falls below 1 mmol/L (4 mg/dl), spasm symptoms may appear. In cases of low blood calcium, the parathyroid glands are stimulated, leading to secondary hyperfunction, which increases the secretion of parathyroid hormone. This results in increased phosphorus excretion in the urine and bone decalcification to compensate for the calcium deficiency. If the compensatory function of the parathyroid glands is insufficient, blood calcium cannot be maintained at normal levels.

Normal serum calcium is divided into diffusible calcium (about 60% of the total calcium) and non-diffusible calcium, the latter being the portion bound to proteins (about 40%). Most non-diffusible calcium is bound to albumin, with the remainder bound to globulin. When the serum H⁺

concentration increases, the calcium bound to proteins decreases. About 80% of diffusible calcium exists in an ionized state (i.e., Ca⁺⁺), while the rest is bound to phosphate, bicarbonate, or citrate Genjie. The main factors affecting serum calcium ion (Ca⁺⁺) concentration are hydrogen ion concentration, phosphate ion concentration, and protein concentration. According to the formula [Ca⁺⁺][HCO^3-][HPO=4]/[H⁺] = k, the higher the hydrogen ion concentration in the blood, the more calcium ions there are, whereas alkalosis has an antagonistic effect. The more phosphate there is, the fewer calcium ions there are. The higher the plasma protein level, the less diffusible calcium and calcium ions there are. Conversely, when plasma protein levels are low, calcium ions are relatively higher. Therefore, in children with nephrotic syndrome, if plasma albumin is significantly reduced, bound calcium also decreases. Even if the total serum calcium drops below the level typically seen in convulsion disorders, the ionized calcium level may not be low enough to cause spasm symptoms. In clinical practice, directly measuring serum calcium ion concentration is challenging, but charts can be used to estimate ionized calcium levels based on total serum calcium and total plasma protein.

Factors that promote a decrease in blood calcium include: (1) Season: The incidence is highest in spring, with the peak number of cases in Beijing occurring from March to May. After winter, infants have little direct exposure to sunlight, and vitamin D deficiency reaches its peak by this time. When spring arrives and sunlight exposure increases, vitamin D levels in the body rise sharply, blood phosphorus increases, and the calcium-phosphorus product reaches 40. A large amount of calcium is deposited in the bones, causing a temporary drop in blood calcium and triggering the condition. (2) Age: Most cases occur in infants under 6 months old. Among the 1,297 cases observed at Beijing Children's Hospital from 1950 to 1955, 41.3% were under 3 months, 25.0% were 4–6 months, 20.4% were 7–12 months, 10.7% were 1–3 years, and 2.6% were 3–14 years old. Infants under 6 months grow the fastest and require more calcium. If dietary intake is insufficient and vitamin D is deficient, the condition is more likely to develop. Early onset is often related to maternal vitamin D deficiency during pregnancy, as the vitamin D stored in a typical infant is sufficient for the first 3 months. (3) Premature infants and formula-fed infants are more susceptible. (4) Chronic diarrhea or obstructive jaundice can reduce the absorption of vitamin D and calcium, leading to low blood calcium.

bubble_chart Clinical Manifestations

1. Manifest Symptoms

(1) Convulsions: These are the most common manifest symptoms in infancy. The characteristic is that the child suddenly experiences convulsions without fever or any other apparent cause. Most patients have multiple convulsions, occurring and stopping repeatedly, with the frequency ranging from 1 to 20 episodes per day, each lasting from a few seconds to about half an hour. When not convulsing, the child appears almost normal. During convulsions, consciousness is usually lost, with rhythmic twitching of the hands and feet, spasms of the facial muscles, upward rolling of the eyes, and incontinence of urine. All these symptoms are indistinguishable from convulsions caused by other diseases. In very young infants, sometimes only facial muscle twitching is observed, which may be the initial symptom of this condition. As for the location of the spasms, they are mostly seen on both sides, occasionally more pronounced on one side.

(2) Hand and Foot Spasms: Hand and foot spasms (Figures 14-22, 14-23) are a distinctive symptom of this disease, characterized by bending of the wrists, straightening of the fingers, the thumb pressing close to the palm, stiff toes with slight bending of the metatarsus, forming an arch-like shape. This symptom is often seen in older infants and children, and rarely occurs in infants under 6 months of age.

(3) Laryngospasm: This mainly occurs in infants under 2 years of age. Laryngospasm causes difficulty in breathing, with prolonged inhalation leading to a hoarse cry. It can result in sudden death due to suffocation. It should be noted that intramuscular injections in children with severe hand and foot spasms may occasionally induce laryngospasm.

(4) Other Symptoms: These often include signs of nervous excitement such as restless sleep, easy startling and crying, and sweating. Fever is not a symptom of the disease itself but is caused by other preceding or concurrent illnesses.

2. Latent Symptoms Common signs are as follows. When only signs are present without the aforementioned symptoms, it may be referred to as latent hand and foot spasm disease.

(1) Facial Nerve Tap Test (Chvostek's Sign): Tapping the exit point of the seventh cranial nerve in front of the ear with a fingertip or small hammer can cause facial muscle contraction, mainly in the upper lip or eyelid. Positive results are obtained in children under 2 years old, except for newborns, as this sign is commonly seen in normal newborns during the first few days or even the first month, even without calcium deficiency. In children over 2 years old, it is occasionally seen in other neurological diseases. With appropriate treatment, all symptoms and signs gradually disappear, except for the facial muscle response, which may persist longer.

(2) Peroneal Reflex: Tapping the peroneal nerve on the outer side of the knee (above the fibular head) with a small hammer causes the foot to contract outward if positive.

(3) Artificial Hand Spasm Sign (Trousseau's Sign): Wrapping the upper arm with a blood pressure cuff and inflating it to temporarily stop the radial pulse can induce hand spasms within 5 minutes if positive.

3. Disease Course With early diagnosis and treatment, most cases can stop convulsions within 1 to 2 days. However, severe laryngospasm can lead to sudden death due to difficulty in breathing, and severe convulsions also carry certain risks. If accompanied by serious infections or infantile diarrhea, the condition may worsen or become prolonged.

bubble_chart Diagnosis

To diagnose hand-foot convulsion syndrome, in addition to noting factors in the medical history such as age, season, and premature labor as disease causes, the following three aspects should be considered. (1) Active symptoms: Convulsions are the most critical in infancy. If there are multiple consecutive convulsions without symptoms or signs of pestilence, this condition should be considered first. In older children, hand-foot convulsions are the most common manifestation. Hand-foot convulsions are a distinctive symptom of this condition, and the diagnosis can be confirmed even in the absence of other symptoms. (2) Signs: As described in the previous section. (3) Qualitative urine calcium tests are mostly negative. This method is simple and practical, making it worth utilizing. (4) When necessary, serum calcium levels can be tested, which are typically reduced to below 1.88 mmol/L (7.5 mg/dL) or even as low as 1–1.25 mmol/L (4–5 mg/dL). At the same time, serum alkaline phosphatase levels are elevated. As for serum inorganic phosphorus, it may be low, normal, or even higher than 2.26 mmol/L (7 mg/dL) (commonly seen in premature infants). This differs from rickets, where blood phosphorus levels are generally reduced. Currently, serum free calcium can be measured quickly and accurately using modern instruments, and its clinical application should be promoted.

bubble_chart Treatment Measures

First is first aid to stop dangerous symptoms such as convulsions or laryngospasm. Next is calcium supplementation to rapidly increase blood calcium levels and prevent the recurrence of convulsions and other symptoms. Then, administer large doses of vitamin D to normalize calcium and phosphorus metabolism, thereby curing the disease.

1. First Aid Measures Convulsions can cause respiratory arrest in children, and laryngospasm is even more dangerous, so they must be quickly controlled. Common methods include immediate intramuscular injection of an adequate dose of phenobarbital sodium, approximately 8mg/kg; or paraldehyde at 1ml per year of age, with a maximum single dose not exceeding 5ml; or a 10% chloral hydrate solution, 4–10ml, administered as a retention enema. Simultaneously, acupuncture therapy can be applied, commonly targeting the philtrum, Hegu (LI4), Shaoshang (LU11), and Yintang (EX-HN3). For laryngospasm, first pull out the tongue tip and perform artificial respiration; if necessary, proceed with endotracheal intubation and artificial ventilation.

2. Calcium Therapy Rapid calcium supplementation is a critical step in emergency management of convulsive syncope cases. Do not delay calcium therapy while waiting for blood calcium test results, as this could endanger the patient’s life. Administer calcium gluconate (10% solution diluted by half) intravenously. Generally, for newborns, use a 5% solution, 10ml per dose; for older infants, use a 10% solution, 10ml per dose, 1–3 times daily, continuing for 2–3 days if necessary. If convulsions stop, switch to oral calcium supplements. For intravenous injection, use a small needle and dilute the calcium gluconate solution with an equal amount of saline or 10–25% glucose solution, then inject slowly (the full dose should take 10 minutes or longer). Rapid IV injection may lead to excessive calcium excretion in urine, reducing efficacy, and could cause temporary hypercalcemia, leading to heart block or even life-threatening complications. For intramuscular injection in infants, divide the 10ml of 10% solution and inject deeply into both gluteal muscles to avoid local reactions like induration or necrosis due to excessive dosage.

While administering calcium gluconate, also give oral calcium chloride. Initially, provide a larger dose (about 1.5–2g), dissolved in 30ml of sugar water or fruit juice to avoid gastric mucosal irritation. After the initial large dose, administer a 10% solution, 5–10ml per dose, 3–4 times daily. The dosage can be adjusted based on symptom severity and age. Calcium chloride therapy should continue for at least one week, switching to calcium gluconate or lactate if necessary. For newborns, follow the same protocol. In severe cases with recurrent convulsions, administer calcium gluconate intravenously, 5–10ml, 2–3 times daily. After convulsions cease, provide oral vitamin D, 1000–2000 IU daily, reducing to 400 IU daily after 3–4 weeks.

Calcium chloride contains 27% calcium and has two effects in the body: (1) increasing blood calcium levels; (2) its strong acidifying effect promotes calcium ionization, rapidly raising blood calcium ion levels and reducing the likelihood of recurrent convulsions.

If a young infant also has diarrhea or concurrent illnesses (e.g., upper respiratory infections) or if an older child has kidney disease, caution is required when using calcium chloride to avoid acidosis. In outpatient settings, prescribe only 2–3 days’ worth of calcium chloride at a time, reassessing before renewing the prescription to prevent

acidosis from prolonged use. Additionally, lactating mothers should generally receive appropriate calcium and vitamin D supplements.

Calcium lactate contains 13% calcium, calcium gluconate contains 9%, and calcium hydrogen phosphate contains 23%. When prescribing calcium supplements, calculate the elemental calcium content.

If the above treatments are ineffective, administer 100,000 IU of vitamin D orally or intramuscularly, with a maximum dose not exceeding 200,000 IU to avoid vitamin D toxicity from excessive dosage.

The methods for preventing hand-foot convulsion are the same as those for preventing rickets. For infantile diarrhea, prompt treatment is necessary to prevent electrolyte imbalance. When infants suffer from various viral hepatitis, liver cells are damaged, leading to impaired formation of 25-hydroxy D, which can easily result in hypocalcemia. Therefore, vitamin D2 or D3 should be supplemented as early as possible.

bubble_chart Prognosis

The methods for preventing hand-foot convulsion are the same as those for preventing rickets. Diarrhea in infants and young children should be treated promptly to prevent electrolyte imbalances. When infants suffer from various types of viral hepatitis, liver cells are damaged, leading to impaired formation of 25-hydroxy D, which can easily result in hypocalcemia. Vitamin D2 or D3 should be supplemented as early as possible.

bubble_chart Differentiation

Differential diagnosis mostly falls into two categories.

The first category is the differential diagnosis of convulsions, details of which can be found in the chapter on convulsions. In the neonatal period, special attention should be paid to birth injuries, congenital brain dysplasia, and sepsis during differentiation. For older infants, particular attention should be given to cerebral symptoms at the onset of various acute sexually transmitted diseases (such as pneumonia and upper respiratory infections), encephalitis, meningitis with low-grade fever (e.g., tuberculous meningitis, and occasionally meningococcal meningitis may temporarily lack high fever), infantile spasms, hypoglycemia, and lead poisoning. In childhood, differentiation should also be made from epilepsy and hypoparathyroidism.

The second category is the differential diagnosis of laryngeal obstruction (see the section on laryngeal obstruction in the respiratory diseases chapter). The laryngospasm of tetany is characterized primarily by inspiratory stridor. If no convulsions are present simultaneously, Foster's sign can be used to aid diagnosis.

In terms of etiology, infantile tetany is mainly caused by vitamin D deficiency leading to hypocalcemia. There are also other forms of tetany with different etiologies, such as hypomagnesemic and alkalotic tetany, which share the same clinical manifestations as infantile tetany. Therefore, it is necessary to differentiate these various forms of tetany. For each case of tetany, clinical issues should be carefully examined, with the most critical point being that the presence of rickets is characteristic of vitamin D deficiency tetany. Below is a brief overview of various forms of tetany other than vitamin D deficiency tetany for differentiation. It should be noted that sometimes multiple etiological factors may coexist in a single case.

1. Tetany due to hypoparathyroidism: For example, accidental removal of the parathyroid glands during thyroid surgery can lead to a deficiency of parathyroid hormone and subsequent hypocalcemia. Neonates may exhibit temporary hypoparathyroidism because the mother's parathyroid function is heightened during fetal development, reducing the need for fetal parathyroid activity. This passive hypofunction may persist for several days postpartum. Some also believe that although neonatal parathyroid function is normal, the body's response to parathyroid regulation is relatively poor, making it difficult to maintain normal blood calcium levels. If neonates are fed cow's milk, the high phosphorus content in milk can hinder calcium absorption, leading to hypocalcemia and eventually tetany. Additionally, there are cases of primary or idiopathic hypoparathyroidism. All three types share a common blood biochemical feature: elevated blood phosphorus, reduced blood calcium, and normal alkaline phosphatase. Treatment should involve dihydrotachysterol or parathyroid hormone.

2. Alkalotic tetany: Hypochloremic alkalosis due to prolonged vomiting or repeated gastric lavage, respiratory alkalosis caused by conditions such as salicylate poisoning leading to deep breathing, or inappropriate fluid therapy, such as intravenous infusion of large amounts of sodium bicarbonate, can all decrease the concentration of calcium ions (Ca⁺⁺) and induce symptoms.

3. Hypomagnesemic tetany is characterized by muscle twitching or convulsions. It is relatively rare and more commonly seen in premature infants and small-for-gestational-age infants. Mothers often have pregnancy toxemia, diabetes, or hyperthyroidism. Occasionally, it occurs in newborns with hemolytic disease who receive exchange transfusions using citrate-anticoagulated blood, where both magnesium and calcium levels in the blood decrease, leading to tetany (normal serum magnesium levels are 0.74–1.25 mmol/L [1.48–2.5 mEq/L]). Prolonged diarrhea or enzyme deficiencies causing intestinal malabsorption can also impair magnesium absorption. Convulsions may also occur due to hyperaldosteronism or primary hypomagnesemia. When serum magnesium falls below 0.74 mmol/L (1.48 mEq/L), symptoms such as facial muscle twitching, athetosis, hypertension, and tachycardia appear. These symptoms do not respond to calcium supplementation but can be controlled with magnesium injections or oral magnesium therapy.

4. Secondary hand-foot convulsions during chronic kidney disease Due to renal insufficiency, the renal tubules' ability to excrete phosphorus is reduced, leading to elevated blood phosphorus levels and consequently decreased blood calcium. Such conditions often involve hypoalbuminemia or chronic acidosis, so hand-foot convulsions rarely occur. However, when serum calcium drops extremely low or when the serum pH rises due to the infusion of alkaline solutions, symptoms such as seizures or hand-foot convulsions may manifest.

5. Hyponatremia and hypernatremia If sodium supplementation is insufficient during dehydration treatment or excessive water intake leads to hyponatremia, neurological symptoms such as drowsiness, vomiting, and seizures may occur. For instance, in infants with diarrhea, even without alkalosis or significant hypocalcemia during the correction of dehydration and acidosis, hypernatremia may develop when blood sodium rises and blood potassium drops, resulting in hand-foot convulsions. Additionally, in cases of neonatal asphyxia or respiratory distress syndrome, administering large amounts of sodium bicarbonate solution may also cause hypernatremia and subsequent seizures.

6. Vitamin B6 deficiency and dependency In early infancy, a lack of vitamin B6 or the occurrence of vitamin B6 dependency can also lead to spasms.