Making a Diagnosis

Many of Gaucher disease's presenting symptoms--from hepatosplenomegaly to bone pain to hematological complications--are also found with other more common diseases (i.e leukemia, lymphoma). It is not unusual for physicians to initially suspect other disorders including:[1]

  • Leukemia
  • Lymphoma
  • Bleeding disorders
  • Osteomyelitis
  • Legg-Calvé-Perthes syndrome
  • Growth pain

In addition, other diseases sometimes present with engorged cells that resemble Gaucher cells.[2] Conditions for which these "pseudo-Gaucher cells" have been detected include:

  • Chronic granulocytic leukemia
  • Multiple myeloma
  • Hodgkin's disease
  • Thalassemia

Signs & Symptoms by Medical Field

Below are clusters of symptoms and signs that may alert physicians to consider Gaucher disease.

General Presentation
Hematology
Gastroenterology/Hepatology
Gynecology
Pediatrics
Orthopedics
Neurology
Cardiology
Dermatology
Ophthalmology

General Presentation

  • Fatigue
  • Easy bleeding and bruising
  • History of frequent infections (self-limiting, not necessarilysevere)
  • Gastrointestinal complaints
  • Splenomegaly
  • Hepatomegaly
  • Bone pain (chronic, waxing and waning over time), “growing pains”
  • Bone crisis – acute episodes of severe pain lasting days or weeks, accompanied by general malaise, fever, leukocytosis, local swelling, tenderness
  • Anemia – chronic
  • Thrombocytopenia – chronic
  • Leukopenia (occasionally significant) or leukocytosis
  • Platelet dysfunction
  • Elevated biochemical markers – angiotensin-converting enzyme (ACE), tartrate resistant acid phosphatase (TRAP), chitotriosidase (chito)
  • Liver function test abnormalities (elevated transaminases)
  • Low cholesterol levels
  • Hypergammaglobulinemia
  • Delayed skeletal growth and/or delayed puberty
  • Dyspnea
  • Signs of chronic inflammation (elevated C-reactive protein, ESR)
  • Cachectic appearance
  • Deformed skeletal habitus

Hematology

  • Anemia (various causes: hypersplenism, bone marrow infiltration, vitamin B12 deficiency, etc.)
  • Thrombocytopenia – chronic
  • Leukopenia (occasionally significant) or leukocytosis
  • Gaucher cells in bone marrow
  • Hypergammaglobulinemia
  • Platelet dysfunction
  • Coagulation factor deficiencies
  • Elevated serum ferritin

Gastroenterology/Hepatology

  • Hepatosplenomegaly
  • Pain attacks localized in side/abdomen
  • Dyspepsia
  • Low energy, chronic fatigue, muscle wasting
  • Elevated biochemical markers – angiotensin-converting enzyme (ACE), tartrate resistant acid phosphatase (TRAP), chitotriosidase (chito)
  • Liver function test abnormalities (elevated transaminases)
  • Signs of chronic inflammation (elevated C-reactive protein, ESR)
  • Gallstones

Gynecology

  • Excessive bleeding during menses
  • Postpartum hemorrhage
  • Mechanical problems from splenomegaly and hepatomegaly during pregnancy
  • Anemia and other hematological abnormalities [see Hematology]
  • Early generalized osteopenia
  • Skeletal joint involvement
  • Pulmonary hypertension

Pediatrics

  • Episodes of severe “growing pains” in a child not going through a growth spurt
  • Declining growth rate (small for age, but not since birth)
  • Delayed puberty
  • Belly complaints (bouts of stinging in the side, dyspepsia)
  • More frequent and serious nose bleeds than normal
  • Inability of a child to keep up with peers in post-school activities, frequent naps after school, fatigue
  • Multiple and extensive bruises and easy bleeding (d.d. battered child)
  • Low impact or multiple fractures (d.d. Perthes/osteonecrosis)
  • Hepatomegaly
  • Splenomegaly
  • Mild hematologic abnormalities (anemia, thrombocytopenia)
  • Elevated biochemical biomarkers (angiotensin-converting enzyme (ACE), tartrate resistant acid phosphatase (TRAP), chitotriosidase (chito)

Orthopedics

  • Unexpected bleeding complication during/after surgery
  • Unexpected infection after surgery
  • Replacement of bone marrow with Gaucher cells (contributing to anemia, leukopenia, thrombocytopenia)
  • Bone pain – chronic
  • Osteonecrosis, more frequent in femoral or humeral heads, but can occur anywhere.
  • Premature pathologic fractures - femoral neck, long bones, vertebrae
  • "Bone crisis" mimicking acute osteomyelitis or sickle cell crisis
  • Erlenmeyer flask deformity
  • Extraosseous bone formation
  • Early generalized osteopenia

Neurology

Neuronopathic Gaucher disease:

  • Oculomotor apraxia
  • Ataxia
  • Seizures
  • Myoclonic epilepsy
  • Cognitive delay

Non-neuronopathic Gaucher disease:

  • Spinal cord or nerve root compression, secondary to vertebral collapse

Cardiology

  • Interstitial myocardial infiltration (rare)
  • Constrictive pericarditis (rare)
  • Calcification of valves (rare)
  • Pulmonary hypertension
  • (rare)

Dermatology

  • Yellow-brown pigmentation of face (rare)
  • Type 2: ichthyosiform or collodion skin

Ophthalmology

Neuronopathic Gaucher disease:

  • Horizontal gaze palsy
  • Strabismus
  • Horizontal nystagmus
  • Optic atrophy leading to blindness (rare)

Non-neuronopathic Gaucher disease:

  • Small deposits in cornea, lens, vitreum or retina (rare)

References:

1. Grabowski GA. Lysosomal storage diseases. In: Braunwald E, Fauci AS, eds. Harrison's Principles of Internal Medicine. 15th ed. New York, NY: McGraw-Hill; 2001:2276-2281.

2. Pastores GM. Pathological features of Gaucher's Disease. Bailliere's Clinical Hematology. 1997; 10(4): 739-749.

3. Beutler E, Grabowski GA. Gaucher disease. In: Scriver C, Beaudet AL, Sly WS, Valle D, eds. The metabolic and molecular bases of inherited disease. 8th ed. New York: McGraw-Hill; 2001:3635-3668.

4. Cox TM, Schofield JP. Gaucher's disease: clinical features and natural history. Bailliere's Clinical Haematology. 1997;10(4):657-689.

Gaucher Registry

For more than a decade, the Gaucher Registry has been a global resource to the medical and patient communities, helping to improve outcomes in patients with Gaucher disease. Learn more about participating in the Gaucher Registry »