Table 1.

Age-dependent presentations of short telomere extrahematopoietic disease

Age group	Immunodeficiency		Liver disease		Lung disease
	Symptoms	Finding	Symptoms	Finding	Symptoms	Finding
Infant	Bloody diarrhea Failure to thriveEnterocolitis Sepsis	Intestinal mucosal atrophy Crypt apoptosis↓ CD19+ B cells↓ IgA	Rare	Rare	Absent	Absent
Adolescent/young adult*	Opportunistic infections(eg, herpes zoster reactivation, primary CMV with retinitis/encephalitis; P jirovecii pneumonia; Candida esophagitis)	↓ CD4+ T cells↓ IgM↓ T-cell repertoire	Splenomegaly Portal HTN Clubbing Dyspnea/hypoxemia Variceal bleeding	Nodular regenerative hyperplasiaA-V malformationsHPSPatchy fibrosis	Usually absent†	Usually absent†
Adult	SCC of the skinCMV viremia and disease after lung transplant P jirovecii pneumonia	↓ CD4+ T cells↓ T-cell repertoire↓ T-cell proliferation	Splenomegaly Portal HTN Clubbing Dyspnea/hypoxemia Atrophic nodular liver Variceal bleeding	Nodular regenerative hyperplasia HPS Overt fibrosis/cirrhosis	Dyspnea/cough Basilar crackles Restrictive PFT findings	IPF-emphysema‡ Other interstitial lung disease

A-V, arteriovenous; CMV, cytomegalovirus; HPS, hepatopulmonary syndrome; HTN, hypertension; IgA, immunoglobulin A; IgM, immunoglobulin M; PFT, pulmonary function test; SCC, squamous cell cancer.

^*These extrahematopoietic manifestations can also present in childhood. In this age group, however, hematologic manifestations are the primary feature (see Figure 2).

^†Pediatric and young adult onset of pulmonary fibrosis has been precipitated historically by the use of ablative regimens in the bone marrow transplant setting, especially those regimens that include busulfan.

^‡This nomenclature reflects the unique spectrum of lung disease phenotypes seen in the short telomere syndromes in which pulmonary fibrosis can occur alone (most commonly) or in combination with emphysema, particularly in female smokers.