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

Fatigue

Easy bleeding and bruising

History of frequent infections (self-limiting, not necessarily severe)

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

Dermatology

Yellow-brown pigmentation of face

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.