Magda Mendez, MD

A 10-month-old previously healthy infant was brought to the emergency department with a runny nose and wet cough that had started a week earlier. He had a tactile fever and decreased oral intake for 2 to 3 days, and 3 to 4 episodes of nonprojectile, nonbilious, non-bloody vomiting for 1 day. His mother reported that he had been extremely fussy and irritable.

F; heart rate, 138 beats/min; respiration rate, 40 breaths/min; blood pressure, 90/48 mm Hg; and O

saturation, 100% while breathing room air. He was crying inconsolably. The anterior fontanel was flat. He had copious nasal secretions with transmitted upper airway sounds. He had one episode of generalized tonic clonic seizure in the ED, which lasted for 20 seconds, with a brief postictal state. He received a loading dose of fosphenytoin and was admitted to PICU to rule out meningitis. A CSF analysis was also done and empiric antibiotic therapy was initiated.

Because viral meningitis was suspected, liver function tests (LFTs) were done. Results indicated elevated levels of ALT (4233 U/L) and AST (3603 U/L). However, PCR analysis of CSF for HSV yielded negative results. Antibiotics were discontinued. The patient’s respiratory distress gradually resolved. Additional testing revealed the cause of the elevated LFTs.


Tests for liver function showed an ammonia level of 43 µmol/L and a normal coagulation profile. Abdominal ultrasonography showed an enlarged liver. A work up was done for probable causes of hepatitis. The serum acetaminophen level was normal, as were results of a hepatitis panel. ANA, anti-smooth muscle antibody, and anti-liver kidney microsomal antibody assays were negative; serum ceruloplasmin and alpha-fetoprotein levels were within normal limits. EBV and CMV panels were also negative. Results of an immunochromatography test for adenoviral antigen were positive.

The onset of hepatic injury in our patient appeared to occur concomitantly or just after respiratory tract infection. Therefore, an infectious cause of acute liver failure was highly possible. Lack of serologic evidence of causes of hepatitis and respiratory infection led us to search for adenovirus in the respiratory secretions.

Several methods are used to detect adenovirus infection depending on the site and severity of infection. Adenovirus infection can be shown by immunochromatography (as in our case) or characteristic pathologic changes -- including intranuclear inclusion bodies in biopsy material, isolation of virus by culture or PCR, or demonstration of an increase in antibody titers.

Our patient was given supportive care. Gradually, his LFTs returned to baseline.

Adenovirus accounts for 5% to 10% of upper and lower respiratory tract infections in infants and children.

 Transmission is by respiratory and fecal oral routes. Approximately 50 serotypes of adenovirus are recognized. Serotypes 1, 2, 3, and 5 cause mainly respiratory illness, and serotypes 40 and 41 cause mainly gastroenteritis.

In healthy children, adenoviral infection causes a benign, self-limited illness. Acute liver failure from adenovirus is rare, and is described especially in immunocompromised patients, in whom it is usually fatal. More virulent types (particularly type 7) can cause respiratory failure, shock and hepatitis in immunocompetent children.

The clinical course of adenovirus infection among healthy children is usually benign but can be complicated by severe or fatal pneumonia, myocarditis, and hepatitis.

We recommend that adenovirus infection be included in the differential diagnosis of fulminant hepatic failure seen in childhood.

1. Ozbay HF, Canan O, Ozcay F, Bilezikci B. Adenovirus infection as possible cause of acute liver failure in a healthy child: a case report. 

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2. Shike H, Shimizu C, Kanegay, et al. Quantitation of adenovirus genome during acute infection in normal children. 

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3.  Peled N, Nakar C, Huberma, H, et al. Adenovirus infection in hospitalized immunocompetent children. 

Articles

Adenovirus infection is usually benign in healthy children, but it can be complicated by severe or fatal pneumonia, myocarditis, and hepatitis. Consider adenovirus infection in children with fulminant hepatic failure.

Adenoviral Hepatitis in an Immunocompetent Child

A 57-day-old girl was brought to her pediatrician because of a scaly rash on her face and scalp. The diagnosis was seborrheic dermatitis; a salicylic acid/sulfur shampoo and topical hydrocortisone were prescribed.

The patient was seen again at 4, 6, and 10 months of age for the same rash. The diagnosis was amended to atopic dermatitis and the treatment was changed to 1% hydrocortisone ointment, to which there was minimal response.

At 1 year of age, the child was brought to the ED with fever and rash. This was the first time fever accompanied the rash. Laboratory test results- including a CBC, blood culture, and urinalysis and culture- were normal. The diagnosis was viral exanthema.

When the child was 13 months old, a whitish coating developed on her tongue and lips. The diagnosis was thrush.Treatment was prescribed but thrush recurred. She again presented at age 14 and 15 months with the same scaly rash. Again, the diagnosis was atopic dermatitis.  Hydrocortisone treatment was continued.

At age 19 months, the patient was again brought for care because of worsening rash. This time, there were dark plaques with edema all over her body. The diagnosis was dermatosis and edema. The child was referred to pediatric dermatology. 

Examination revealed poor dentition, hypopigmented macules on the child’s back and lateral chest, ichthyosiform rash on both lower extremities with fine scale, and spoon-shaped nail changes. A punch biopsy showed dermal fibroplasia, dermal melanophages, and hints of interface dermatitis-findings consistent with dyskeratosis congenita. 

The child was referred for genetic, neurologic, hematologic, and dental counseling. A pediatric geneticist proposed the diagnosis of autosomal recessive form of dyskeratosis congenita.

The child is being followed regularly by dermatology, neurology, and hematology.

With X-linked inheritance, only males display symptoms. With autosomal dominant inheritance, one of the patient’s parents is affected. This was not the case with our patient; her parents had a 25% chance of having another child with dyskeratosis congenita.
  



 In dyskeratosis congenita, abnormal skin pigmentation and nail changes are usually the first symptoms; these often become manifest before a child’s 10th birthday. These changes are followed by bone marrow failure, which occur before the patient reaches age 20. Up to 80% of affected patients show signs of bone marrow failure by age 30.

Dyskeratosis congenita is 2 to 3 times more common in males than females because the main mechanism of inheritance is X-linked.

Fewer than 1% of patients have autosomal recessive inheritance

 (as in our case). Telomere abnormalities have been reported in a few patients with other inherited bone marrow failure syndromes, including Fanconi anemia, Shwachman Diamond syndrome, and Diamond Blackfan anemia, but the degree of telomere shortening is usually not as profound as in dyskeratosis congenita.

 The primary cause of death (in 60% to 70% of cases) is from bone marrow failure and immunodeficiency resulting in fatal infections before third decade of life.

Dyskeratosis Congenita: Take-home points 

• Dyskeratosis congenita is an inherited bone marrow failure syndrome. In its classic form, it is usually characterized by the mucocutaneous triad of abnormal skin pigmentation, nail dystrophy, and leukoplakia  (


 • It is associated with a very high risk of aplastic anemia, myelodysplastic syndrome, leukemia, and solid tumors. Patients have very short germ line telomeres, and approximately half have mutations in 1 of 6 genes encoding proteins that maintain telomere function. 
 • Hematopoietic stem cell transplantation is the only cure for patients with severe bone marrow complications.

 
 • Rash and thrush are a very common presenting complaint in pediatrics. If patient presents with above mentioned triad (abnormal pigmentation, nail dystrophy, and leukoplakia), keep this entity in mind as a diagnostic possibility. 


 1. Savage SA, Alter BP. Dyskeratosis congenita. 

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 2. Alter BP, Giri N, Savage SA, Rosenberg PS. Cancer in dyskeratosis congenita. 

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 3. Dokal I. Dyskeratosis congenita. 

American Society of Hematology Education Program Book.

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 4. Gadalla SM, Cawthon R, Giri N, et al. Telomere length in blood, buccal cells, and fibroblasts from patients with inherited bone marrow failure syndromes. 

2010; 2:867–874.
 5. Jyonouchi S, Forbes L, Ruchelli E, Sullivan KE. Dyskeratosis congenita: a combined immunodeficiency with broad clinical spectrum-a single-center pediatric experience. 

2011;22:313-319.
 6.  Bessler M. Du HY, Gu B, Mason PJ. Dyskeratosis congenita and telomerase.

Abnormal pigmentation, nail dystrophy, and leukoplakia may signal dyskeratosis congenita.

Author | Magda Mendez, MD

Articles

Adenoviral Hepatitis in an Immunocompetent Child

Dyskeratosis Congenita: An Inherited Bone Marrow Failure Syndrome