Sanjad-Sakati Syndrome (SSS)

Sanjad-Sakati Syndrome (SSS)—also called HRD syndrome (hypoparathyroidism–retardation–dysmorphism)—is a very rare, inherited condition. Children are born with underactive parathyroid glands (hypoparathyroidism), which causes low blood calcium, high blood phosphate, and seizures or muscle spasms early in life. Many children have slow growth, small head size, developmental delay, and distinct facial features (such as deep-set eyes, thin upper lip, beaked nose, and small chin). The condition is autosomal recessive, meaning both parents silently carry one non-working copy of a gene and, together, can pass it to a child. The usual cause is a change (variant) in the TBCE gene, which helps cells build their internal “scaffolding” (microtubules). Problems in this system affect growth and the parathyroid glands, which leads to the low-calcium state. Genetic Rare Disease CenterOrphaPMCNature

Sanjad-Sakati syndrome is a rare genetic condition that starts before birth and continues through life. Children with this condition usually have three major problems that appear together. The first problem is congenital hypoparathyroidism, which means the parathyroid glands make too little parathyroid hormone (PTH) from birth. The second problem is poor growth and developmental delay. The third problem is distinctive facial and skeletal features that doctors call “dysmorphism.” Because PTH is too low, blood calcium becomes too low and blood phosphate becomes too high. This low calcium can trigger muscle spasms and seizures in the newborn period and later in childhood. PMC

The root genetic cause is a change (a “pathogenic variant”) in a gene called TBCE (tubulin-specific chaperone E). This gene helps cells build microtubules, which are tiny internal “rails” that help cells grow, divide, and move parts around. When TBCE does not work well, some tissues—especially the parathyroid glands, bones, and the developing brain—do not form or function normally. The condition is autosomal recessive, which means a child must inherit one non-working copy of TBCE from each parent to be affected. NaturePMC

Doctors first recognized that many children with the same clinical picture in Middle Eastern families shared an identical small deletion in TBCE (called c.155-166del, sometimes nicknamed the “Bedouin founder mutation”). Families in other countries can have different TBCE changes. PMC+1PubMed

Sanjad-Sakati syndrome is closely related to Kenny–Caffey syndrome type 1 (KCS1). These two conditions are “allelic,” meaning they involve the same TBCE gene and can share some bone features, such as long-bone changes. Sanjad-Sakati syndrome more often shows microcephaly, more severe developmental delay, and usually less striking bone thickening than classic Kenny–Caffey patterns. PMC+1

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Types

Doctors do not use strict “subtypes” the way some diseases do. Instead, they talk about clinical patterns along a spectrum. This helps families understand what to expect.

1. Classic Sanjad-Sakati (HRD) pattern.
   This is the common pattern with early-life hypocalcemia from low PTH, seizures or tetany, growth failure, developmental delay, and characteristic facial features. PMC

2. Milder or attenuated pattern.
   Some children have the same gene change but a milder course. They still have low PTH and low calcium but may have fewer seizures, better growth with careful therapy, or less obvious facial features. (This reflects the natural spectrum seen in rare genetic conditions.)

3. Overlap with Kenny–Caffey syndrome type 1 (KCS1).
   Because HRD and KCS1 share the TBCE gene, some children show features that overlap, such as long-bone changes (cortical thickening and medullary canal narrowing), while still having the HRD triad. PMC+1

4. By timing of diagnosis.
   Some babies are diagnosed in the newborn period because of seizures and low calcium. Others are diagnosed in infancy when growth falters or when facial features and developmental concerns become clearer. AccessAnesthesiology

5. By underlying mutation.
   Many affected families from the Middle East share the same c.155-166del deletion. Families elsewhere may have different TBCE variants. Doctors sometimes group cases by the exact variant for genetic counseling and research. PMC+1

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Causes and drivers

Important: The single primary cause of Sanjad-Sakati syndrome is having two pathogenic variants in the TBCE gene. The 20 items below put that core cause in plain language and also list the downstream mechanisms and risk modifiers that together create the full picture seen in the child.

1. Biallelic TBCE variants.
   A child inherits one non-working TBCE gene from each parent, so TBCE protein cannot do its job well. This is the root cause. Nature

2. Faulty microtubule assembly.
   TBCE helps fold tubulin. Without it, microtubules are unstable, and developing cells cannot grow and organize normally. This harms many tissues at once. Nature

3. Under-developed parathyroid glands.
   If parathyroid glands are small or function poorly, PTH stays low, and calcium control breaks down. This is why calcium drops and phosphate rises. PMC

4. Low PTH signaling.
   Even when some PTH is made, it may be too little for the body’s needs, so the kidneys and bones cannot keep blood calcium in a safe range. PMC

5. Hypocalcemia.
   Low calcium makes nerves and muscles over-excitable. This can trigger tetany, carpopedal spasms, and seizures. This is a direct downstream driver of many symptoms. PMC

6. Hyperphosphatemia.
   Low PTH lets phosphate rise, which makes it even harder to keep calcium normal. This worsens neuromuscular irritability. PMC

7. Prenatal growth restriction.
   Because many cells do not work normally during pregnancy, babies are often small for dates and continue to grow poorly after birth. PMC

8. Neurodevelopmental impact.
   Abnormal microtubule function plus repeated neonatal hypocalcemia can affect brain development, leading to developmental delay or intellectual disability. PMC

9. Characteristic craniofacial growth pattern.
   Facial bones and cartilage grow in a distinctive way when cell scaffolding is abnormal, creating the typical facial features doctors recognize. PMC

10. Long-bone modeling changes in the same gene family.
    Some children with TBCE-related disease have thick outer bone and narrow marrow canals (an overlap with KCS1). The same gene explains this pattern. PMC

11. Founder mutation in some regions.
    The c.155-166del TBCE deletion is common in several Middle Eastern populations, which raises the chance that two carriers will meet. PMC+1

12. Autosomal recessive inheritance.
    Each sibling of an affected child has a 25% chance to also be affected when both parents are carriers. This is a cause of recurrence in families. Nature

13. Consanguinity increases risk (a population driver).
    When parents are related, the chance of sharing the same rare variant is higher, so an affected child is more likely in that population. AccessAnesthesiology

14. Possible pituitary involvement in some cases.
    Some reports show pituitary under-development and pituitary hormone deficits in TBCE-related disease, which can further slow growth. EMROMalaCards

15. Chronic hypocalcemia can calcify brain areas over time.
    Long-standing low calcium can lead to intracranial calcifications, which may contribute to movement problems or seizures. PMC

16. Dental enamel and mineralization problems.
    Abnormal calcium–phosphate balance can disturb tooth development and enamel strength, adding to the facial-skeletal pattern. PMC

17. Low magnesium can worsen low PTH and low calcium.
    If magnesium is low, PTH secretion falls further, so hypocalcemia becomes harder to correct. This is a common physiologic modifier to check. PMC

18. Vitamin D deficiency makes calcium control harder.
    If vitamin D is low, intestinal calcium absorption drops, and the body struggles even more to maintain safe calcium levels. (This is a modifier, not the core cause.) Pediatrics

19. Illness, stress, or high phosphate intake can tip calcium lower.
    Fevers, diarrhea, or high-phosphate feeds can worsen hypocalcemia in an already fragile calcium–phosphate balance. (Again, modifiers, not the root cause.) PMC

20. Very rare TBCE-negative look-alike reports exist.
    A few reports describe HRD-like features without a TBCE mutation, suggesting there may be extremely rare undiscovered genetic causes with a similar clinical picture. MalaCards

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Symptoms and everyday signs

1. Seizures in the newborn period or infancy.
   Low calcium makes the brain more likely to have seizures. Seizures may be subtle or obvious. PMC

2. Tetany and carpopedal spasms.
   Hands and feet may cramp and curl because the nerves and muscles are over-excitable when calcium is low. PMC

3. Irritability and jitteriness.
   Babies can be fussy and trembly because low calcium makes muscles twitch easily. PMC

4. Breathing or voice problems from laryngospasm.
   A tight spasm in the voice box area can cause stridor or brief pauses in breathing. PMC

5. Feeding difficulties.
   Poor suck, frequent vomiting, or poor weight gain are common early signs. PMC

6. Failure to thrive and short stature.
   Children often remain small and gain weight slowly unless carefully managed. PMC

7. Developmental delay.
   Motor and speech milestones may be late. Early therapy helps but delays are common. PMC

8. Intellectual disability.
   Cognitive disability can range from mild to severe and may be worsened by early untreated hypocalcemia. PMC

9. Microcephaly (small head size).
   Head size is often below the normal range. PMC

10. Characteristic facial features.
    A long narrow face, deep-set small eyes, a beaked nose, small jaw, and thin lips with a long philtrum are commonly described. PMC

11. Small hands and feet with tapered fingers.
    Hands and feet may look small with long, thin, sometimes curved fingers. PMC

12. Dental anomalies.
    Enamel can be thin, and tooth eruption can be delayed or irregular. PMC

13. Bone changes (in some children).
    Some children show long-bone modeling changes related to the same TBCE pathway, especially in the allelic KCS1 spectrum. PMC

14. Abnormal movements or stiffness with illness or stress.
    When sick or crying hard, tetany may be more obvious because calcium balance is more fragile. PMC

15. Seizures later in life if calcium control slips.
    Children and adults can have breakthrough seizures if supplements are missed or if another illness upsets calcium balance. PMC

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Diagnostic tests

A) Physical examination

1. Growth measurements.
   Doctors measure weight, length/height, and head size and plot them on charts. Children with Sanjad-Sakati syndrome are often below average for age, and this helps track progress over time. PMC

2. Facial and cranial inspection.
   The face, skull shape, jaw size, and eye position are examined carefully. The typical pattern helps point toward the diagnosis when combined with lab results. PMC

3. Neurologic exam for tone and reflexes.
   The doctor looks for increased startle, tremor, or brisk reflexes that can appear with low calcium. A baseline neurologic exam also guides seizure evaluation. PMC

4. Musculoskeletal and extremity exam.
   Hands, feet, fingers, and long bones are checked for size and shape. Some children have small hands and tapered fingers, and some have bone modeling changes on X-ray. PMC

B) Bedside/manual clinical signs

5. Chvostek sign.
   The clinician gently taps the facial nerve in front of the ear. In hypocalcemia, the facial muscles twitch. This is a quick bedside clue to low calcium. PMC

6. Trousseau sign.
   A blood-pressure cuff is inflated on the arm. In hypocalcemia, the hand may cramp into a characteristic posture after a few minutes. This supports the diagnosis of neuromuscular irritability. PMC

7. Observation for carpopedal spasm during stress.
   Crying, hyperventilation, or fever can bring out hand or foot spasms when calcium is low. Careful bedside observation documents this sign. PMC

8. Developmental screening at the bedside.
   Simple age-appropriate tasks (for example, tracking with the eyes, head control, grasping, babbling) help document developmental delay so early therapies can start.

C) Laboratory and pathological tests

9. Ionized calcium (and total calcium).
   Ionized calcium directly shows the biologically active calcium level. It is usually low in Sanjad-Sakati syndrome during hypocalcemic episodes. PMC

10. Serum phosphate.
    Phosphate is typically high when PTH is low. This supports the pattern of hypoparathyroidism. PMC

11. Parathyroid hormone (PTH).
    PTH is inappropriately low or “not high enough” for the degree of hypocalcemia. This is the central biochemical clue. PMC

12. Serum magnesium.
    Low magnesium can further suppress PTH and make hypocalcemia resistant to therapy, so it must be measured and corrected. PMC

13. Vitamin D status (25-hydroxyvitamin D).
    Vitamin D deficiency can worsen hypocalcemia and must be treated if present to stabilize calcium. Pediatrics

14. Urinary calcium/creatinine ratio.
    This test helps monitor for high urine calcium, especially when children receive calcium and active vitamin D. It guides safe dosing and helps prevent kidney problems. (Monitoring is standard in hypoparathyroidism care.) PMC

15. Genetic testing for TBCE.
    Sequencing and targeted deletion analysis (including the c.155-166del “founder” deletion where relevant) confirm the diagnosis and allow family carrier testing. NaturePMC

D) Electrodiagnostic tests

16. Electrocardiogram (ECG).
    Low calcium can prolong the QT interval. An ECG is a quick, painless way to check the heart’s electrical pattern and to monitor during treatment. (Hypocalcemia–QTc links are standard physiology.) PMC

17. Electroencephalogram (EEG).
    If seizures occur, an EEG helps show seizure activity and guides anti-seizure treatment plans while calcium is corrected. PMC

E) Imaging tests

18. Brain CT or MRI.
    Chronic hypocalcemia can lead to intracranial calcifications; neuroimaging can show these changes and also check for structural features that have been reported (for example, corpus callosum hypoplasia in some cases). PMCEMRO

19. Long-bone X-rays.
    In some TBCE-related cases there is cortical thickening and medullary canal narrowing. X-rays help document skeletal involvement across the HRD/KCS1 spectrum. PMC

20. Renal ultrasound.
    Because therapy uses calcium and active vitamin D, doctors monitor the kidneys for nephrocalcinosis. Ultrasound is a safe way to check for calcium deposits over time. (This is standard hypoparathyroidism follow-up.) PMC

Non-pharmacological treatments (Therapies & others)

(each item: what it is, purpose, how it helps)

1. Care team coordination & caregiver training.
   Purpose: Keep calcium steady, prevent emergencies.
   Mechanism: Regular plans with pediatrics, endocrinology, nutrition, dentistry, and therapy services reduce missed doses and spot early warning signs (jitteriness, spasms).

2. Emergency plan for low calcium.
   Purpose: Act fast if seizures or tetany occur.
   Mechanism: Families learn signs of hypocalcemia and when to go to the ER; providers keep IV calcium protocols ready. NCBI+1

3. Physiotherapy.
   Purpose: Improve strength, posture, and fine/gross motor skills.
   Mechanism: Repetitive, guided movement strengthens muscles, counters hypotonia, and supports milestones.

4. Occupational therapy (OT).
   Purpose: Daily living skills (feeding, dressing, writing).
   Mechanism: Task-specific training, hand-function work, and adaptive tools.

5. Speech-language therapy.
   Purpose: Communication, feeding/oral-motor support.
   Mechanism: Language stimulation, oromotor exercises, and safe-swallow strategies.

6. Early-intervention education.
   Purpose: Maximize learning during the brain’s most flexible period.
   Mechanism: Individualized programs boost cognition, behavior, and social skills.

7. Feeding therapy & dietetic support.
   Purpose: Address poor weight gain, reflux, or oral aversion.
   Mechanism: Stepwise texture work, safe calories, and calcium-balanced meal planning.

8. Regular dental/orthodontic care.
   Purpose: Manage enamel issues, malocclusion, or delayed eruption.
   Mechanism: Preventive dental care decreases pain/infection and supports nutrition.

9. Vision & hearing checks.
   Purpose: Catch correctable problems early that may worsen learning.
   Mechanism: Glasses/ear tubes when needed improve engagement and speech.

10. Safe home modifications.
    Purpose: Reduce fall/aspiration risks and support mobility.
    Mechanism: Rails, non-slip flooring, cushioned corners, and adaptive seating.

11. Structured sleep routine.
    Purpose: Improve growth, learning, and seizure threshold.
    Mechanism: Consistent sleep/wake times and calming routines stabilize the nervous system.

12. Hydration and regular bowel routine.
    Purpose: Help kidneys handle calcium load and prevent constipation from calcium supplements.
    Mechanism: Water and fiber limit stone risk and GI discomfort.

13. Sunlight with skin safety.
    Purpose: Support vitamin D status without burns.
    Mechanism: Short, safe daylight exposure plus sunscreen balance vitamin D and skin protection.

14. Low-phosphate food pattern (when advised).
    Purpose: Counter high phosphate from hypoparathyroidism.
    Mechanism: Limiting cola drinks and processed meats reduces phosphate load (used alongside medicines if needed). Oxford Academic

15. Lower sodium intake.
    Purpose: Reduce urinary calcium losses (helps if hypercalciuria occurs during therapy).
    Mechanism: Less salt → less calcium lost in urine; pairs with thiazide strategy when prescribed. PMC

16. Routine vaccinations.
    Purpose: Prevent serious infections in a child with growth/nutritional vulnerabilities.
    Mechanism: Builds targeted immunity; follows national schedule.

17. Mental health & social work support.
    Purpose: Lower caregiver stress and improve adherence.
    Mechanism: Counseling, respite, and benefits navigation.

18. Genetic counseling.
    Purpose: Future pregnancy planning and family testing.
    Mechanism: Explains autosomal-recessive inheritance and testing options. Genetic Rare Disease Center

19. School-based supports (IEP/504).
    Purpose: Access to therapy and learning accommodations.
    Mechanism: Legally structured help for speech, OT, PT, and extra time.

20. Transition planning (adolescence → adult care).
    Purpose: Keep calcium management safe during growth and puberty.
    Mechanism: Handover to adult endocrinology and dentistry with a written plan. Oxford Academic

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Drug treatments

Doses are typical ranges. Always individualize with the child’s clinician.

1. Calcitriol (active vitamin D3).
   Class: Active vitamin D analog.
   Typical dose: Infants 0.04–0.08 µg/kg/day; children often 0.25–2 µg/day, titrated every 2–4 weeks.
   When: Daily, divided if higher doses.
   Purpose: Core therapy for congenital hypoparathyroidism.
   Mechanism: Replaces the active hormone that parathyroid normally drives; raises calcium and lowers phosphate by enhancing intestinal calcium absorption.
   Key side effects: High calcium/urine calcium, kidney stones; needs close labs. E-ApemEsceoOxford Academic

2. Oral calcium carbonate (or calcium citrate if low stomach acid or on PPIs).
   Class: Calcium salt.
   Typical target elemental calcium: 45–100 mg/kg/day split 3–4 times daily; adjust to labs/symptoms.
   When: Daily; with meals improves absorption.
   Purpose: Maintain calcium between low-normal and mid-normal.
   Mechanism: Provides elemental calcium directly.
   Side effects: Constipation, gas; excessive dosing → hypercalcemia/hypercalciuria. StarshipMedscape

3. Intravenous calcium gluconate (10%) for acute symptomatic hypocalcemia (seizures/tetany).
   Class: IV calcium.
   Typical emergency use: Bolus 2–5 mmol elemental Ca over 10–20 min, then infusion; or ~15 mg/kg elemental Ca over 4–6 h per guideline.
   Purpose: Stops seizures and tetany quickly.
   Mechanism: Immediate restoration of ionized calcium.
   Risks: Tissue injury with extravasation; cardiac monitoring needed. NCBIOxford Academic

4. Magnesium (oxide or sulfate when low).
   Class: Magnesium supplement/replacement.
   Typical oral elemental Mg: 2.5–5 mg/kg up to 10–20 mg/kg per dose, repeated 3–4×/day as needed; IV options exist for severe deficiency.
   Purpose: Correct hypomagnesemia, which can block PTH release and worsen hypocalcemia.
   Mechanism: Restores magnesium so parathyroid and vitamin D signaling work.
   Side effects: Diarrhea (oral), flushing (IV). Royal Children’s HospitalNCBI

5. Thiazide diuretic (e.g., hydrochlorothiazide).
   Class: Thiazide.
   Typical pediatric range: 0.5–1 mg/kg/day (often divided); some use 12.5–25 mg/day in older kids/teens.
   When: If urine calcium is high on therapy.
   Purpose: Reduce hypercalciuria and protect kidneys.
   Mechanism: Increases calcium reabsorption in distal tubule; often paired with low-salt diet.
   Side effects: Low potassium/sodium, dizziness; may add amiloride if hypokalemia. FrontiersPMC

6. Amiloride (adjunct to thiazide when potassium runs low).
   Class: Potassium-sparing diuretic (ENaC blocker).
   Typical pediatric use: ~0.625 mg/kg/day for <20 kg or 5–10 mg/day if >20 kg (varies by source/indication).
   Purpose: Prevent thiazide-induced hypokalemia and may further reduce urine calcium.
   Mechanism: Blocks ENaC to spare potassium and reduce calcium loss.
   Side effects: Hyperkalemia, GI upset—use with lab monitoring. PediatricsFrontiers

7. Cholecalciferol (vitamin D3) maintenance (adjunct).
   Class: Nutrient supplement (not a replacement for calcitriol).
   Typical intake (RDA): 400 IU/day (infants) and 600 IU/day (children ≥1 yr), unless the endocrinologist chooses otherwise.
   Purpose: Keeps body stores of 25-OH-vitamin D adequate so response to calcitriol is predictable.
   Mechanism: Maintains substrate for vitamin D pathways; target levels decided by clinician.
   Side effects: Excess can worsen hypercalcemia. Office of Dietary Supplements

8. Phosphate binders (e.g., sevelamer, calcium acetate) in selected cases.
   Class: Phosphate binders.
   Typical: Sevelamer often 800–1600 mg with meals in older children/teens when truly needed; pediatric approvals vary by age and kidney status—use specialist guidance.
   Purpose: Lower serum phosphate if diet + core therapy fail.
   Mechanism: Binds dietary phosphate in the gut to reduce absorption.
   Side effects: GI bloating/constipation; large pill burden. NCBIU.S. Food and Drug Administration

9. Potassium citrate (for stone risk if hypercalciuria persists).
   Class: Urinary alkalinizer/citrate replacement.
   Dose: Individualized; often weight-based mEq/kg/day; used by nephrology if stones or low urine citrate.
   Purpose: Increases urinary citrate, which binds calcium and helps prevent stones.
   Mechanism: Citrate complexes calcium and raises urine pH. Sap

10. Rescue benzodiazepine (e.g., intranasal midazolam) per seizure plan (ER/medical supervision).
    Class: Antiseizure rescue.
    Use: For prolonged seizures while calcium correction is underway.
    Purpose: Immediate seizure control.
    Mechanism: Enhances GABA inhibition.
    Note: Not disease-specific; long-term antiseizure drugs are only used if epilepsy persists for reasons beyond hypocalcemia.

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Dietary “molecular” supplements

These support calcium–magnesium–phosphate balance or general nutrition. Use only with your clinician; many are adjuncts to the prescription plan.

1. Calcium carbonate (elemental Ca).
   Dose: Typically counted toward 45–100 mg/kg/day elemental Ca target.
   Function: Builds serum calcium.
   Mechanism: Supplies absorbable calcium. Medscape

2. Calcium citrate (elemental Ca).
   Dose: Same elemental Ca targets; sometimes better if low stomach acid or on PPIs.
   Function: Alternative calcium source.
   Mechanism: Citrate salt absorbs well with meals.

3. Vitamin D3 (cholecalciferol).
   Dose (RDA guides): 400 IU/day (infants), 600 IU/day (children).
   Function: Maintains stores of 25-OH-vitamin D.
   Mechanism: Supports bones and immune modulation; calcitriol remains the main active therapy. Office of Dietary Supplements

4. Magnesium (preferably glycinate or chelate for GI tolerance).
   Dose: 2.5–5 mg/kg up to 10–20 mg/kg per dose, 3–4×/day when replacing; clinician sets total.
   Function: Corrects low magnesium that can block PTH effects.
   Mechanism: Restores cofactor for calcium regulation. Royal Children’s Hospital

5. Protein/energy supplements (e.g., pediatric formulas).
   Dose: As prescribed by dietitian to reach age-appropriate calories.
   Function: Improves growth in children with feeding difficulty.
   Mechanism: Sufficient energy/protein enables catch-up growth.

6. Multivitamin without extra vitamin A.
   Dose: Age-appropriate daily.
   Function: Covers common micronutrient gaps.
   Mechanism: Supports overall growth and immunity.

7. Iron (only if deficiency is proven).
   Dose: Clinician-directed (often ~3 mg/kg/day elemental iron for deficiency).
   Function: Corrects anemia that can worsen fatigue/development.
   Mechanism: Replenishes hemoglobin iron.

8. Zinc (only if deficient).
   Dose: Based on age/weight and labs.
   Function: Supports immunity and growth.
   Mechanism: Restores zinc-dependent enzymes.

9. Omega-3 DHA/EPA (diet first; supplement if intake is poor).
   Dose: Age-appropriate per pediatric guidance.
   Function: Supports neurodevelopment.
   Mechanism: Incorporates into neuronal membranes.

10. Probiotics (for feeding intolerance/antibiotic-associated diarrhea).
    Dose: Product-specific CFU; short courses.
    Function: GI comfort and nutrient absorption.
    Mechanism: Modulates gut microbiome.

(Strongest disease-specific evidence among these is for calcium, vitamin D, and magnesium; the rest depend on individual nutrition status.)

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Regenerative / stem-cell drugs

I can’t responsibly list “immunity-booster” or stem-cell drugs for SSS because none are established or approved for this condition. Using such products outside trials can be risky and misleading. Here is what is evidence-based and safer:

1. Full routine immunization on schedule (influenza, pneumococcal as indicated).

2. Nutritional optimization (enough protein, vitamins D/C, zinc only if deficient).

3. Prompt treatment and prevention of low calcium, which itself lowers seizure threshold and overall resilience. Oxford Academic

4. Consider IV magnesium when very low, because low Mg can block PTH and keep calcium low. NCBI

5. Infection-control habits (hand hygiene, dental care).

6. Clinical trials/registries if available—talk to your genetics/endocrine team.

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Surgeries

1. Gastrostomy tube (G-tube) placement.
   Procedure: Small feeding tube placed through the abdomen.
   Why: Severe feeding difficulty or failure to thrive despite therapy.

2. Anti-reflux surgery (fundoplication) with or without G-tube.
   Procedure: Tightens valve at top of stomach.
   Why: Refractory reflux with poor weight gain/aspiration risk.

3. Strabismus (eye alignment) surgery.
   Procedure: Adjusts eye muscles.
   Why: Persistent misalignment to improve vision development.

4. Hernia repair (inguinal/umbilical).
   Procedure: Day-surgery closure of defect.
   Why: Prevents incarceration; common pediatric surgery if a hernia is present.

5. Dental surgeries/extractions or orthodontic procedures.
   Procedure: Corrects severe crowding, caries, or malocclusion.
   Why: Pain prevention, better chewing and nutrition.

Preventions

1. Never run out of calcitriol/calcium; keep a refill buffer.

2. Lab monitoring as scheduled (calcium, phosphate, magnesium, kidney function, urine calcium). Oxford Academic

3. Low-salt diet if urine calcium runs high; it helps thiazides work if they’re used. PMC

4. Avoid high-phosphate foods/drinks (colas, processed meats) if instructed—keeps phosphate in range. Oxford Academic

5. Hydrate well to protect kidneys from high urine calcium.

6. Consistent sleep to support brain, growth, and seizure threshold.

7. Prompt fever/infection care—illness can destabilize calcium control.

8. Dental hygiene (fluoride, regular cleanings) to prevent pain and feeding setbacks.

9. Sun safety + vitamin D plan—balance sensible daylight with sunscreen; follow clinician’s plan for D. Office of Dietary Supplements

10. Genetic counseling for family planning in autosomal-recessive conditions. Genetic Rare Disease Center

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When to see a doctor urgently

• Seizure, stiff muscles/tetany, twitching, or severe cramps.

• New vomiting, very poor feeding, or dehydration.

• Unusual sleepiness, irritability, or behavior change.

• Fever with trouble breathing or fast heart rate.

• Signs of high calcium (rare but possible if over-treated): constipation, extreme thirst, peeing a lot, confusion.

• Kidney pain or blood in urine (possible stones).

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What to eat  and what to avoid

Eat more (if your clinician agrees):

1. Dairy (milk, yogurt, cheese) for calcium.

2. Leafy greens like kale/bok choy (calcium; lower oxalate than spinach).

3. Calcium-set tofu and fortified plant milks.

4. Canned fish with bones (sardines, salmon).

5. Almonds and sesame (tahini) in modest portions.

6. Magnesium-rich foods (pumpkin seeds, legumes). Office of Dietary Supplements

7. Whole-food proteins (eggs, beans, poultry, fish) to support growth.

8. High-fiber fruits/veg to ease constipation from calcium.

9. Plenty of water throughout the day.

10. Age-appropriate vitamin D sources (fortified milk, eggs; supplements only as prescribed). Office of Dietary Supplements

Limit/avoid:

1. Cola and processed meats (high phosphate). Oxford Academic

2. Very salty snacks (chips, instant noodles)—worsen urinary calcium. PMC

3. Excess spinach/rhubarb/beets (high oxalate; may raise stone risk).

4. Mega-doses of vitamin D or calcium without labs—risk of hypercalcemia. Office of Dietary Supplements

5. Unregulated “immune boosters.”

6. Energy drinks (caffeine can worsen dehydration).

7. Sugary beverages (empty calories).

8. Very low-fluid intakes.

9. Alcohol/tobacco exposure (for teens/household—harms growth and bone).

10. Any supplement not cleared with your clinician.

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Frequently Asked Questions

1. Is SSS curable?
   No. It is a lifelong genetic condition. But symptoms are very manageable, especially calcium control, when families and clinicians work together. Genetic Rare Disease Center

2. What causes the low calcium?
   Underactive parathyroid glands from the TBCE-related disorder reduce PTH, so the body can’t keep calcium in the normal range. PMC

3. Why does phosphate run high?
   Low PTH reduces phosphate excretion by the kidneys, so blood phosphate goes up while calcium goes down. Oxford Academic

4. Will my child always need medicines?
   Usually yes—calcitriol and calcium are the core of treatment, with magnesium if low. Doses change as children grow. E-Apem

5. Can seizures stop?
   Yes—correcting calcium and magnesium is the first and most important step; seizure medicines are used only when needed. NCBI

6. Are thiazide diuretics safe?
   They can help when urine calcium is high, but need lab checks for potassium and sodium; sometimes amiloride is added. Frontiers

7. What calcium level should we aim for?
   Guidelines often target low-normal to mid-normal serum calcium to avoid both symptoms and side effects; your clinician sets a personalized target. Oxford Academic

8. How often are labs needed?
   More often during dose changes; then periodically to check calcium, phosphate, magnesium, creatinine, and urine calcium. Oxford Academic

9. Is vitamin D3 the same as calcitriol?
   No. Calcitriol is the active hormone; vitamin D3 (cholecalciferol) maintains body stores. Many children need both, as directed. E-Apem

10. Can diet alone fix the calcium?
    Diet helps, but medicine is essential because the parathyroid glands are underactive. Food cannot replace calcitriol in this condition. Oxford Academic

11. Any special dental concerns?
    Yes. Enamel and alignment issues are common; routine dental care prevents infections and helps nutrition.

12. Are “stem-cell” or “regenerative” cures available?
    No approved therapies exist for SSS. If you see claims online, be cautious and talk to your care team about clinical trials. (Safety first.)

13. Can we prevent kidney stones?
    Keep calcium in the target range, drink water, limit salt, and treat hypercalciuria (thiazide ± amiloride) if it appears. Frontiers

14. Will my child grow normally?
    Growth is often smaller than average, but good nutrition, therapy, and steady calcium control help each child reach their personal best.

15. What about future pregnancies?
    Because SSS is autosomal recessive, each pregnancy has a 25% chance to be affected when both parents are carriers. Genetic counseling explains options. Genetic Rare Disease Center

Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical  history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.

The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members

Last Updated: August 24, 2025.