Tetralogy of Fallot

Disease Description (Causes and Symptoms)

• Definition summary: An inherited basement membrane disorder caused by genetic variants in type IV collagen (alpha3, alpha4, alpha5), characterized mainly by kidney involvement (hematuria, proteinuria, progressive chronic kidney failure), sensorineural hearing loss, and ophthalmic abnormalities.
• Causes: Mutations in the COL4A3, COL4A4, and COL4A5 genes. The most common inheritance pattern is X-linked (COL4A5), but autosomal recessive and dominant forms also exist.
• Pathophysiology: Deficient or abnormal proteins cause the glomerular basement membrane (GBM) to become thin or undergo lamellation (splitting), resulting in glomerular filtration impairment and progressive kidney damage. It also affects the inner ear, retina, conjunctiva, and other structures with the same basement membrane.
• Main symptoms
  • Hematuria (microscopic or gross hematuria beginning in childhood)
  • Gradual development of proteinuria and decline in kidney function → some develop chronic kidney failure (ESRD) from childhood or adolescence
  • Sensorineural hearing loss (usually gradually progressive after adolescence, occurring in approximately half of patients)
  • Ophthalmic findings: anterior lenticonus (a highly specific finding), retinal changes, and corneal abnormalities (rare)
• Course and prognosis summary: Morbidity and rate of progression vary according to the genotype and sex. X-linked males and patients with the autosomal recessive form tend to progress more rapidly to severe disease and ESRD. Female carriers are generally mildly affected, but some may experience progression.

Treatment Methods and Precautions

• There is no definitive cure. The goals are to preserve kidney function and manage complications.
• Drug treatment
  • RAAS blockers (ACE inhibitors or ARBs): Because they reduce proteinuria and help preserve kidney function, they should be started as early as possible when appropriate (in both children and adults). Treatment goals are to minimize proteinuria and appropriately control blood pressure.
  • Other measures: Restriction of high-protein and high-salt intake is recommended; diuretics and antihypertensive medications may be used in combination when necessary.
• Hearing and vision management
  • Hearing loss: Regular hearing tests; hearing aids or cochlear implants may be considered in severe cases.
  • Ophthalmology: Ophthalmic surgery or correction may be considered if lens abnormalities, particularly anterior lenticonus, develop.
• Renal replacement therapy
  • If the disease progresses to ESRD, dialysis or kidney transplantation is required. Prognosis after transplantation is generally good, but complications related to an anti-GBM immune response may rarely occur (reported with certain genotypes).
• Genetic testing and family management
  • Confirmation of the diagnosis and determination of the genotype, family screening, and genetic counseling are recommended.
• Lifestyle management and precautions
  • Avoid nephrotoxic medications such as NSAIDs and aminoglycosides.
  • Regularly monitor blood pressure and proteinuria, and check kidney function during infections or dehydration.
  • Women who are carriers or planning pregnancy should receive preconception counseling (kidney function may change during pregnancy).
• Complications
  • ESRD, hypertension, nephrotic syndrome, progressive hearing loss, and worsening vision (which may lead to blindness in severe cases).

Checklist Before an Outpatient Visit (Including Preparation Materials and Example Questions)

• Materials/documents to bring
  • List of medications currently being taken (including prescription drugs, over-the-counter drugs, and herbal medicines)
  • Recent blood pressure records (including home measurements)
  • Recent urinalysis results (urine protein and microscopic findings), blood test results (including creatinine and eGFR), and previous test records
  • Findings from any previous kidney tissue examination (biopsy) or genetic test results, if available, preferably as copies
  • Family history information (whether relatives have hematuria, ESRD, hearing loss, or ophthalmic disease, and relatives' ages, etc.)
  • Records of changes in symptoms (when hematuria began and when hearing or vision changes began)
• Items to check yourself in advance of the outpatient visit
  • Whether there has recently been hematuria or foamy urine (proteinuria)
  • Whether there is hearing loss or tinnitus, visual field abnormalities, eye pain, or other symptoms
• Situations that should be reported to the doctor first during the outpatient visit
  • Worsening acute hematuria, edema/shortness of breath (suggesting kidney failure or nephrotic syndrome), or a sudden severe increase in blood pressure

Examples of General Questions to Ask the Doctor

• "What are my current kidney function levels (creatinine and eGFR) and proteinuria level, and what is the expected progression in the future?"
• "Should I start an ACE inhibitor (or ARB)? What are the expected benefits and side effects?"
• "Do you recommend genetic testing for my family? What are the screening methods and timing?"
• "If I am planning a pregnancy, what should I be careful about?"
• "If I experience changes in my hearing or vision, which specialist should I see and when?"

Examples of Disease-Specific Questions

• "What is my family's genetic test result (or genotype), and could you explain the inheritance pattern and probability of passing it on to our children?"
• "If proteinuria is observed, when (at what level) should an ACE inhibitor be started, and what are the target blood pressure and proteinuria levels?"

(If necessary, attach test results or family history information, and we can also organize more specific consultation questions and a management plan.)