Understanding the Epidemiology of LAM

LAM occurs almost exclusively in women. Cystic radiographic changes in men with TSC have been described in some TSC series, but only three biopsy documented cases of TSC-LAM have been reported in men. There is one documented case of Sporadic LAM (S-LAM) reported in a man. All races are affected. In one LAM Foundation survey of 480 patients, Caucasians made up 90%, Asians 3.5%, African Americans 3%, and Hispanics, 2%. TSC does not differentially affect particular ethnic groups, and access to health care, education, and the internet likely play important roles in the skewed ethnic distribution for LAM reflected in The LAM Foundation database.

The prevalence of S-LAM is roughly estimated to be approximately 3-5 per million people (30,000-50,000 patients worldwide), based on organized attempts to identify LAM patients in England, the United States and France by saturation mailings to all pulmonary physicians identified in each country. The incidence of TSC-LAM can be calculated from population data (Table 1). TSC occurs in approximately 1/6000 births, and the estimated number of TSC patients on earth is about 1-2 million. The worldwide prevalence of TSC-LAM therefore most likely falls in the range of 180,000 to 240,000 people, given the equal gender distribution of TSC and recent findings that 30-40% of women with TSC have cystic changes consistent with LAM.

Although TSC-LAM appears to be roughly 6-8 times as common as S-LAM, patients with TSC-LAM represent only a small fraction of the LAM patients seen in pulmonary clinics. Approximately 13% of the 832 patients registered with The LAM Foundation (as of 9/2004) reported a history of TSC. Furthermore, LAM is a major clinical problem in only about 5% of TSC patients and is a primary health priority for only a few (<10) of the 300 patients in the Tuberous Sclerosis Clinic at the University of Cincinnati. There are several possible explanations for the low visibility of TSC-LAM patients in the LAM community, including that other TSC-related health priorities may overshadow pulmonary symptoms or that TSC-LAM behaves differently from S-LAM. Although screening of asymptomatic women with TSC will provide a mechanism to study the natural history of LAM, we must remain cognizant that TSC-LAM and S-LAM may not be exactly the same disease.

Table 1.  Comparison of TSC-LAM and Sporadic LAM

 

TSC-LAM

Sporadic LAM

Estimated  # patients on earth

250,000

30,000-50,000

Reported in males

+

+

Reported in children

+

+

Ascertainment

mostly by screening

dyspnea and pneumothorax

Germ line TSC mutations

+

-

Both hits = somatic mutations

-

+

Heritable

+

-

TSC1/TSC2

mutations reported

33%/66%

0%/100%

Angiomyolipomas

70-80%

multiple/bilateral

30-50%

single/unilateral

MMPH

+

very rare

CNS/skin/eye/cardiac lesions

+

-

Retroperitoneal, thoracic

adenopathy

+

+

Dyspnea

less common

more common

Chylothorax

less common

33%

Pneumothorax

less common

66%

Respiratory failure

less common

more common

Abbreviations-CNS; central nervous system

MMPH; Multifocal micronodular pneumocyte hyperplasia

TSC1/TSC2 – TSC genetic loci