Usmle hot points review

Danil Hammoudi.MD



1/ Fanconi’s syndrome


renal tubular defect, spare the glomeruli but result in a generalized pattern of tubular dysfunction  may lead to the loss of:

·        Phosphate

·        Calcium

·        Glucose

·        Amino acids


·        excessive urine production and urination

·        excessive thirst;

·        dehydration;

·        constipation;

·        anorexia nervosa;

·        vomiting;

·        elevated levels of glucose, phosphate, calcium, uric acid, amino acids, and protein (especially beta2-microglobulin and lysozyme) in the urine;

·         elevated levels of chloride

·         decreased levels of phosphate and calcium in the blood;

·         excessively acidic blood.




This reabsorption step is defective in Fanconi's syndrome.

As a consequence, substances that are normally reabsorbed, like glucose, amino acids, small proteins, water, calcium, potassium, magnesium, bicarbonate, and phosphate, are lost and the body becomes overly acidic.

The most noticeable indirect consequences of impaired reabsorption are the bone diseases, rickets and osteomalacia

. Rickets affects children and is associated with bone deformities, failure to grow, and difficulty walking.

 If a person acquires Fanconi's syndrome as an adult, the bone disease is termed osteomalacia and is accompanied by severe bone pain and spontaneous fractures.

Unlike rickets due to malnutrition, these diseases cannot be reversed with vitamin D.

Muscle weakness and occasional paralysis are other indirect consequences of the ineffective reabsorption

The genetic diseases known to give rise to Fanconi's syndrome are

·        cystinosis (the most common cause in children),

·        galactosemia,

·        glycogen storage disease,

·         hereditary fructose intolerance,

·         Lowe syndrome,

·        Wilson disease,

·        tyrosinemia,

·         medullary cystic disease,

·         vitamin D dependency,

·        familial idiopathic Fanconi's syndrome


Environmental assaults that cause Fanconi's syndrome include :

·        exposure to heavy metals (like cadmium, lead, mercury, platinum, uranium),

·        certain drugs (like outdated tetracycline and gentamicin),

·         other substances (like Lysol, paraquat, toluene, the amino acid lysine taken as a nutritional supplement),

·        kidney transplantation

Fanconi's syndrome is also known as Fanconi syndrome, renal Fanconi syndrome, Fanconi renaltubular syndrome, and Lignac-de Toni-Debre-Fanconi syndrome. Fanconi's anemia is, however, a totally different disease.



  • multiple myeloma
  • amyloidosis
  • sjogren's syndrome
  • nephrotic syndrome
  • renal transplantation
  • vitamin D deficiency
  • lead
  • mercury
  • cadmium
  • uranium
  • strontium
  • tetracycline
  • maleic acid
  • cystinosis
  • wilson's disease
  • galactosemia
  • hereditary fructose intolerance
  • tyrosinemia
  • lowe's syndrome
    • types of insults:

1. Primary Fanconi Syndrome

        • 1. Sporadic
        • 2. Hereditary
          • autosomal dominant
          • autosomal recessive
          • x-linked recessive

2. Secondary Fanconi Syndrome

        • 1. Inborn Errors of Metabolism
          • Cystinosis
          • Galactosemia I & III
          • Glycogenosis - GSD Ia & XI
          • Hereditary Fructose Intolerance
          • Lowe Syndrome
          • Tyrosinemia I
          • Wilson Disease
        • 2. Acquired Diseases
          • 1. Proteinuric States
            • Multiple Myeloma
            • Nephrotic Syndrome
          • 2. Tubular Toxins
            • heavy metals (cadmium, lead, mercury)
            • drugs (outdated tetracycline, gentamicin, azathioprine)
          • 3. Others
            • Hyperparathyroidism (Primary & Secondary)
            • Interstitial Nephritis
            • Transplanted Kidney
            • Tumors
            • Vitamin D Dependant Rickets



1. Serum

2. Urine

1. Cardinal Features

2. Others

3. Imaging Studies

1. Skeletal X-Rays


Fanconi’s syndrome :aquired

·        An inherited blood disease

·        bone marrow fails to produce all types of blood cells.

·        Lack of white blood cells results in predisposition to infections,

·        while lack of platelets and red blood cells result in bleeding, and fatigue (anemia), respectively.

·        It is also associated with a broad variety of physical anomalies.

·        (Fanconi’s anemia is distinct from Fanconi’s syndrome, a rare kidney disorder in which nutrients are lost through the urine.)



Fanconi's syndrome; familial

Alternative names:

deToni-Debre-Fanconi syndrome

Fanconi syndrome is an impairment in proximal tubular function of the kidney.

 This impairment causes certain compounds, which should be absorbed back into the bloodstream by the kidneys, to be excreted in the urine instead.

Some compounds that may be lost in the urine include glucose, amino acids, uric acid, and phosphate. Loss of these compounds can cause problems such as

·        growth failure,

·        decreased bone mineralization (rickets),

·        and abnormal bone mineralization (osteomalacia).

·        Type two renal tubular acidosis (RTA) occurs when too much bicarbonate is excreted in the urine, causing excess acid in the blood (acidosis).

·         Another problem that may result is dehydration caused by excess urination.


Fanconi syndrome can be genetic or acquired later in life.

  Common causes of Fanconi syndrome in children are genetic defects impairing the body’s ability to break down certain compounds, such as

·        the amino acid cystine (Cystinosis),

·        fructose (fructose intolerance),

·        galactose (galactosemia),

·         glycogen (glycogen storage diseases).

·          Cystinosis is the most common cause of Fanconi syndrome in children.

·          Lowe’s disease (oculocerebrorenal syndrome), a rare genetic disorder of the eyes, brain, and kidneys, can also cause Fanconi syndrome.

·          Another genetic defect that can cause Fanconi syndrome is Wilson’s disease, which causes copper to collect in the kidneys, liver, eyes, and other organs.

·          Similarly, exposure to heavy metals, such as lead poisoning, can cause Fanconi syndrome, even when there is no genetic disease.



·        In adults, Fanconi syndrome can be caused by various acquired disorders that damage the tubules of the kidneys. 

·        As in children, this damage can be caused by exposure to heavy metals such as lead, mercury, and cadmium.

·        The kidneys can also be damaged by prescribed drugs such as cidofovir (used to treat AIDS-related cytomegalovirus disease),

·        gentamicin, tetracycline used after its expiration date, and azathioprine (used to suppress the immune system after organ transplantation or to treat certain autoimmune disorders).

·        Kidney damage leading to Fanconi syndrome can also be caused by dysproteinemias, diseases in which there are abnormal protein deposits in the kidney. 

·        These include multiple myeloma, light chain deposition disease, and primary amyloidosis.

·        It can also occur as a result of a kidney transplant.  Sometimes, in both children and adults, the cause of Fanconi syndrome is not known. 



Many different diseases can cause Fanconi syndrome. 

  The underlying disease should be treated if there is a treatment available.  For example:

Most disorders causing Fanconi syndrome cannot be treated directly. 

 In these cases, the symptoms of the disease are treated instead.

  Symptomatic therapy includes:


1. Primary Fanconi Syndrome

1. Medical

2. Prognosis

2. Secondary Fanconi Syndrome



Fanconi's syndrome can be reversible. Fanconi's syndrome caused by kidney transplantation usually reverses itself within the first year after transplant surgery.

When caused by a toxin in the environment, Fanconi's syndrome generally can be reversed by removing the causative agent from the patient's environment.

 If it is caused by a genetic disease, it can usually be reversed by treating the disease.

However, if Fanconi's syndrome is not treated or if treatment is unsuccessful, the kidneys can fail.

  Key Terms

•  Acidosis

Condition where the body is more acidic than normal; associated with headache, nausea, vomiting, and visual disturbances.

•  Fanconi's anemia

An inherited form of aplastic anemia.

•  Filtrate

The part of filtered material that flows through the filter.

•  Idiopathic

Refers to a disease of unknown cause.

•  Polydipsia

Excessive thirst.

•  Polyuria

Excessive production of urine.



         I.            Pathophys

                             A.            Deficient Renal Tubular excretion

                             B.            Results in:

                                                      1.            Aminoaciduria

                                                      2.            Glycosuria

                                                      3.            Hypophosphatemia

  1. Causes
    1. Hereditary idiopathic form
    2. Acquired form
      1. Medications
      2. Heavy metals
      3. Multiple Myeloma
      4. Amyloidosis
      5. Renal transplantation
  2. Sx
    1. Children
      1. Polydipsia
      2. Malnutrition
      3. Increased susceptibility to infection
    2. Adults
      1. Pain in weight bearing joints
      2. Dehydration
  3. Signs
    1. Growth Retardation
    2. Developmental Delay
    3. Bony deformities similar to Rickets
    4. Waddling gait
    5. Pathologic fractures
  4. Lab
    1. Urine
      1. Aminoaciduria
      2. Cystinuria
      3. Glycosuria
      4. Phosphaturia


         I.            GLYCOSURIA

       II.            Hyperglycemia Causes of glucose in urine

                             A.            See Hyperglycemia

  1. Renal Causes of glucose in the urine
    1. Signs suggestive of Renal Tubular disease
      1. Serum Glucose <180 mg/dl
      2. Glucose Tolerance Tests are normal
      3. Ketosis absent
    2. Specific Causes
      1. Fanconi's Syndrome
      2. Toxic renal tubular disease
        1. Lead toxicity
        2. Mercury toxicity
        3. Degraded Tetracycline
      3. Inflammatory renal disease
        1. Acute Glomerulonephritis
        2. Nephrosis
      4. Increased GFR without tubular damage
  2. False Positive Glucosuria
    1. Ascorbic acid
    2. Nalidixic acid
    3. Cephalosporins
    4. Probenacid


         I.            Causes

                             A.            Starvation

                             B.            Diabetic Ketoacidosis

                            C.            Total Parenteral Nutrition (TPN)

                            D.            Insulin

                             E.            Nasogastric Suction (NG Suction)

                             F.            Diuretics

                            G.            Vomiting

                             H.            Vitamin D deficiency

                                 I.            Hypoparathyroid

                              J.            Pseudohypoparathyroid

                             K.            Medications

                                                      1.            Corticosteroids

                                                      2.            Aluminum Hydroxide antacids

                              L.            Gram negative sepsis

  1. Evaluation
    1. Check Urinary Phosphate excretion (Urine pHosphorus)
    2. Low Urine pHosphorus: under 100 mg/d (FePO4 under 10%)
      1. Internal Redistribution
        1. Glucose administration
        2. Alkalosis
        3. DKA recovery
      2. GI Losses
        1. Malabsorption
        2. Vomiting
        3. Diarrhea
        4. Aluminum or Magnesium antacids
    3. High Urine pHosphorus: over 100mg/d (FePO4 over 20%)
      1. Check for wasting in urine of other electrolytes
        1. Glucose
        2. Amino acid
        3. Uric Acid
        4. Bicarbonate
      2. Electrolyte Wasting present
        1. Fanconi's Syndrome
          1. Idiopathic
          2. Sporadic
          3. Familial
        2. Cystinosis
        3. Amyloidosis
        4. Multiple Myeloma
        5. Wilson's Disease
        6. Nephrotic Syndrome
        7. Cadmium toxicity
        8. Acute lead toxicity
      3. Electrolyte Wasting absent
        1. Increased Serum Calcium
          1. Primary or ectopic Hyperparathyroidism
        2. Normal or Low Serum Calcium
          1. Secondary Hyperparathyroidism
          2. Androgen or Estrogen treatment
          3. Thiazide Diuretics
          4. Vitamin D resistant rickets
          5. Post Acute Tubular Necrosis
          6. Post-transplant
  2. Management
    1. SEE Phosphorus Replacement