OVERVIEW
Fanconi syndrome, also known as Fanconi syndrome, osteochondroplasia-renal glycosuria-aminoaciduria-hyperphosphaturia syndrome, and multiple renal tubular dysfunction disorders, is a group of syndromes caused by hereditary or acquired abnormalities of the proximal renal tubules.
Causes
There are many causes of this syndrome, which can be divided into two categories: primary and secondary. Primary Fanconi syndrome is divided into three types: infantile, adult, and brush border deficiency. Secondary Fanconi syndrome can be secondary to a genetic disorder or acquired. The majority of cases in young children are genetically related, while in adults it is more likely to be secondary to an immunologic disorder, metal poisoning, or kidney disease.
Symptoms
The disease is rare, and most of the symptoms appear in adulthood, including renal glycosuria, multiple amino aciduria, hypercalciuria, renal loss of sodium, hypophosphatemia, proximal tubular acidosis, hypouricemia, tubular proteinuria, hypokalemia (muscle weakness, flaccid paralysis, periodic paralysis, etc.), hypocalcemia (tetany), etc. The disease may be associated with chronic hypercalcemia. Prolonged hypocalcemia can cause secondary hyperparathyroidism and renal bone disease. The most prominent clinical manifestations of this disease are vitamin D deficiency disease in children and osteochondrosis in adults. The clinical manifestations of secondary Fanconi syndrome are essentially the same as those of the primary, but may have clinical manifestations of its various disease types. The clinical manifestations of this syndrome are complex, and are described below according to their clinical types:
1. Primary Fanconi syndrome
There are 3 types:
(1) Adult-type Fanconi syndrome starts after 10 to 20 years of age, with a variety of renal tubular dysfunctions, such as all-amino aciduria, glucosuria, phosphaturia, hyperchloremic acidosis, and hypokalemia. The prominent symptom is achondroplasia, and ketosis may be present in a few cases Renal failure may occur in the late stage.
(2) Infantile Fanconi syndrome Mostly develops at 6 to 12 months of age, with polyuria, irritable thirst, dehydration, constipation, weakness, refusal of food, fever, growth retardation, renal amino aciduria, and may have anti-vitamin D rickets and severe malnutrition.
(3) Idiopathic brush border deletion Fanconi syndrome Because of the complete loss of glucose and various amino acid carrier systems, the clearance rate of these substances is close to the glomerular filtration rate.
2. Secondary Fanconi syndrome
Most of them have primary disease, and the manifestations of different causes are different.
(1) Cystine storage disease The Fanconi syndrome caused by cystine storage disease is different from the Fanconi syndrome caused by other reasons, which is often characterized by potassium loss, dehydration, polydipsia and osmotic diuresis. Clinically, it can be divided into 3 types: ① Infantile or nephropathic type: cystine is deposited in lysosomes of various tissues, and various symptoms appear due to renal tubular injury, and most of the children start to develop around 6 months old, with polyuria, irritable thirst, constipation, polydrinking, vomiting, refusal of food, emaciation, developmental disorders, and repetitive fevers due to dehydration, and vitamin D deficiency disease and dwarfism can occur. Photophobia due to cystine deposits in the cornea and conjunctiva and peripheral pigmentation of the fundus may cause peripheral retinopathy. Hypothyroidism, diabetes mellitus, splenomegaly, cerebral edema, and myopathy may also be manifested. Renal tubular dysfunction is manifested as renal concentration dysfunction, hydrogen ion excretion dysfunction, and the urine cannot be acidified to pH 5.5 or below, resulting in renal tubular acidosis. Childhood or intermediate type: Onset around 10 years of age, slower progression, less severe bone disease, no dwarfism. Tissue cystine content is much lower than that of infantile type, and the cystine content in leukocytes is 30 times normal. It may also show renal lesions or even develop uremia, and skeletal deformities, photophobia, retinopathy, and cystine-induced splenomegaly may also be produced. Fanconi syndrome is not obvious. (iii) Adult type No manifestations of nephropathy, with other organ dysfunctions predominating. The adult form can be further divided into acute and chronic forms, the former being similar to the infantile form and the latter to the pediatric form.
(2) Lowe’s syndrome This syndrome was first reported by Lowe in 1952, also known as eye-brain-renal syndrome, and is characterized by ocular symptoms, congenital cataracts (bilateral) with congenital glaucoma (bull’s-eye), severely impaired visual acuity, nystagmus and photophobia.
Examination
1. Urine examination
Urine is alkaline, low specific gravity, positive for urinary protein and glucose, increased urinary calcium, potassium, phosphorus and uric acid, and renal all-amino acid urine.
2. Blood test
Blood calcium, phosphorus, potassium, uric acid, carbon dioxide binding capacity decreased, blood chloride increased, blood alkaline phosphatase increased.
3. Routine X-ray examination
Osteoporosis, bone deformity, urinary tract stone can be found.
4. Other examinations
In Fanconi syndrome caused by cystine storage disease, there are cystine crystals in the cornea by bone marrow slides, leukocytes, analysis of crystals in the rectal mucosa, or slit lamp examination.
Diagnosis
Diagnosis is confirmed on the basis of etiology, clinical manifestations and relevant investigations.
Treatment
1. Treatment of etiology
Secondary Fanconi syndrome should be treated for the underlying disease. wilson’s disease or heavy metal poisoning can be treated by promoting toxic excretion, and genetic metabolic disorders can be treated by dietary management to reduce metabolic toxicant deposition and mitigate damage to the renal tubules. Cystine storage disease secondary to Fanconi syndrome should be treated with a low cystine diet and symptomatic therapy. Bone lesions can be treated with vitamin D2 or vitamin D3 or hydroxycholecalciferol. Dehydration and acidosis should be treated accordingly. In the early stages, potassium citrate sodium solution can be given orally. Penicillamine can be tried to eliminate cystine, but can not reduce intracellular cystine deposits; dithiothreitol (DDT) is not effective, cysteine effect is better.
2. Symptomatic treatment
(1) Correct acidosis according to the loss of bicarbonate to supplement the alkaline agent, available bicarbonate, citrate, lactate, etc., given in divided doses, in order to restore the normal level of bicarbonate in the blood as a standard. Sodium supplementation can aggravate hypokalemia, and should be detected; it is advisable to supplement potassium at the same time for those who already have hypokalemia. If the alkaloid dosage is too large for the patient to tolerate, hydrochlorothiazide (dihydroclonidine) can be added, which can shrink the extracellular fluid and promote the reabsorption of bicarbonate, but caution should be taken to prevent the decrease of glomerular filtration rate.
(2) Correcting hypovolemia Fanconi syndrome often results in dehydration due to polyuria. In addition to treating the cause of the disease, adequate salt-containing fluids (including sodium, potassium, and calcium) should be supplemented, which can be given orally at regular intervals, with temporary additions if necessary.
(3) Correct hypophosphatemia, neutral phosphate should be taken in divided doses. The dosage can be reduced if there is diarrhea or abdominal discomfort. Note that phosphorus supplementation can aggravate hypocalcemia and bone disease, so it should be combined with vitamin D or 1,25(OH)2D3, and should be started from a small amount, and gradually increased to the full amount. In order to prevent renal calcification, urinary calcium excretion should be monitored.
(4) Hypouricemia, aminoaciduria and proteinuria Generally do not require treatment.
(5) Renal failure Dialysis or renal transplantation is appropriate.