Successful liver transplantation in short telomere syndromes without bone marrow failure due to DKC1 mutation

Abstract

Short telomere syndromes are a heterogenous spectrum of disorders leading to premature cellular aging. These may involve bone marrow failure, adult‐onset idiopathic pulmonary fibrosis, and liver disease, and classical entities such as dyskeratosis congenita. We report a patient who presented with common variable immunodeficiency at 3 years of age and autoimmune cytopenias at 8 years of age. He was found to have short telomeres, and genetic testing confirmed a hemizygous mutation NM_001363.4: c.‐142C > G in DKC1 gene. He subsequently developed cirrhosis with severe portal hypertension and hepatopulmonary syndrome, prompting liver transplantation at 11 years of age. He remains well 10 years after transplant with no progression of bone marrow failure or progressive lung disease. In conclusion, short telomere syndromes should be considered as a potential cause of pediatric liver disease of unknown etiology, and in severe cases, isolated liver transplantation may be both appropriate and successful.

Case Report: A Missense Mutation in Dyskeratosis Congenita 1 Leads to a Benign Form of Dyskeratosis Congenita Syndrome With the Mucocutaneous Triad

“…We also found 13 variants of DKC1 in Asia with 100% male ( 7 , 9 , 13 , 20 , 23 , 28 , 32 , 35 , 36 , 40 ), 52 variants in non-Asia with 84.8% male ( 1 , 8 , 10 – 14 , 16 – 19 , 21 , 24 – 26 , 29 , 31 , 33 , 34 , 37 , 38 , 41 , 42 , 44 , 45 ), and 10 variants with unknown nationality ( 3 , 4 , 30 ). Asians develop DC at a younger age than non-Asians, between 4.3 and 46 years old ( 1 , 7 – 12 , 14 , 16 – 24 , 26 , 28 , 29 , 31 – 35 , 38 – 42 ).…”

“…We also found 13 variants of DKC1 in Asia with 100% male ( 7 , 9 , 13 , 20 , 23 , 28 , 32 , 35 , 36 , 40 ), 52 variants in non-Asia with 84.8% male ( 1 , 8 , 10 – 14 , 16 – 19 , 21 , 24 – 26 , 29 , 31 , 33 , 34 , 37 , 38 , 41 , 42 , 44 , 45 ), and 10 variants with unknown nationality ( 3 , 4 , 30 ). Asians develop DC at a younger age than non-Asians, between 4.3 and 46 years old ( 1 , 7 – 12 , 14 , 16 – 24 , 26 , 28 , 29 , 31 – 35 , 38 – 42 ). The incidence of the mucocutaneous triad (skin pigmentation, nail dystrophy, and mucosal leukoplakia), bone marrow failure, thrombocytopenia, and telomere shortening in Asia are similar to that of non-Asia ( Table 3 ; 1 , 3 , 4 , 7 – 12 , 14 , 16 – 24 , 26 , 28 – 35 , 38 – 42 , 45 , 46 ).…”

Combined lung and liver transplantation for noncirrhotic portal hypertension with severe hepatopulmonary syndrome in a patient with dyskeratosis congenita

“…The time to resolution of arterial hypoxemia after LT is highly variable, and there is no clear indication on how hypoxemia affects the prognosis after LT 19‐22 . Additionally, the outcome of LT is unclear in “DC patients” with HPS since there are only a few reported cases in the literature 5,6,9 . Furthermore, as observed in our case, no such severe HPS has been reported.…”

“…Thus, an increasing number of patients with DC require solid organ transplantation. Recently, lung transplantations and LTs have been performed in patients with DC with pulmonary fibrosis and chronic liver disease, respectively 5‐9 . It has been reported that some patients with telomeropathies require multiple solid organ transplantations 10 …”

Outcomes following liver transplant in adults with telomere biology disorders

“…(3) There have been three previous reports describing liver transplantation in TBD, only one of which took place in an adult. (4)(5)(6) We present four additional adult cases of liver transplantation for hepatic complications of telomere biology disorders. (Table 1)…”