Alport syndrome

Alport syndrome is a hereditary disease characterized by affecting the kidneys, sight and hearing, producing alterations in all these systems. It is a disease that affects 1 in 50,000 people. The disease can present three types of hereditary pattern, being the form that is linked to the X chromosome the most frequent, with 85% of the cases of Alport syndromes. In the other cases, inheritance can be autosomal recessive (10% of cases) or, less frequently, autosomal dominant (5% of patients).

How is it produced?

Alport syndrome is characterized by an alteration of type IV collagen that affects the basement membranes of many organs, mainly the kidneys, hearing, sight and skin. When there is a failure in the correct synthesis of collagen, the membranes are altered and weakened, which is why they cannot perform their function adequately. This, in practice, translates into kidney failure that in the long run can be chronic and terminal; an affectation of the auditory membranes, with which a hearing loss or sensorineural deafness occurs; and a weakness of some layers of the eyeball, which favors the appearance of various ophthalmological pathologies.

The most common form of Alport syndrome is the one that is linked to the X chromosome, so that the affectation occurs mainly in men and at an early age. Fewer women suffer from this disorder, they are usually asymptomatic carriers, since the function of the X chromosome free of the mutation for the gene that codes for collagen IV prevails; in case of suffering from the disease, the symptoms appear in older ages and with less severity. In the case of autosomal inherited Alport syndromes, whether recessive or dominant, both sexes are affected equally.

Symptoms

The symptoms of Alport syndrome appear at an early age, presenting the patient with microhematuria, bleeding in the urine that is not visualized, which in the long run can lead to. Likewise, the impairment of the kidney's filtering capacity causes fluids to accumulate and the patient presents edema, especially in the lower extremities and around the eyes.

The involvement of the ear causes the patient to suffer from progressive bilateral high-frequency sensorineural hearing loss, between 2000 and 8000 Hz, which can lead to total and irreversible deafness. It occurs in 80-90% of patients with Alport syndrome and appears before 40 years of age.

The ocular involvement typical of Alport syndrome is the so-called anterior lenticone, which consists of a lesion that causes the lens to protrude towards the anterior chamber of the eye due to the weakness of collagen, a fact that alters the visual capacity of the patient. Other frequent ocular affections are megalocornea, and myopia.

Diagnosis

The diagnosis of Alport syndrome will be suspected in patients with a family history of it who present alterations in renal function as well as hearing and vision problems. There is a series of criteria to diagnose it, and a minimum of them must be met to establish the diagnosis.

These criteria are:

• Family history of hematuria or nephritis
• Persistent hematuria with no other justifying cause
• Bilateral sensorineural deafness
• Eye injuries
• Progressive or end-stage chronic kidney failure
• Leiomyomatosis
• Collagen mutations or other genetic or immunohistochemical alterations

One should be performed that allows assessing kidney function. Likewise, an audiometry will be performed to assess the degree of hearing loss and a complete ophthalmological study to assess the existence of ocular involvement, such as anterior lenticon, megalocornea or cataracts.

The diagnosis of certainty will be provided by the renal biopsy, where own changes will be seen in the glomeruli and tests can be carried out with the tissue that allow the diagnosis to be reached. Since collagen IV involvement also occurs in the skin, sometimes a skin biopsy can also be performed for diagnosis, which is less aggressive than a kidney biopsy.

Treatment

The treatment of Alport syndrome will be based on taking care of its different affected devices and systems. Renal failure should be controlled by a nephrologist, assessing the need for the use of diuretics, adequate nutrition and good blood pressure control. In advanced cases, dialysis or even kidney transplantation may be necessary. Kidney transplantation is the only curative treatment for kidney disease for most patients, but 3-4% of transplant patients have developed another kidney disease called Goodpasture syndrome.

The hearing loss or deafness characteristic of Alport syndrome is irreversible, so the best therapeutic option, depending on the degree of hearing loss, will be hearing aids or patient education in lip reading or sign language.

Visual disturbances, such as cataracts or lenticonus, can be surgically corrected if necessary.

Preventive medicine

Alport syndrome is an inherited disorder, so there are no preventive measures to avoid it. If there are direct relatives diagnosed with it, it is important to be aware of the signs and symptoms that the children of the affected people may present and make them routine checks of both kidney function and hearing and vision.