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Fatal Hepatic Hemorrhage from Peliosis Hepatis with X-linked Myotubular Myopathy

Hagiwara, Shin-ichiro*; Kubota, Mitsuru*; Sakaguchi, Keita*; Hiwatari, Erika*; Kishimoto, Hiroshi; Kagimoto, Seiichi*

Journal of Pediatric Gastroenterology and Nutrition: May 2015 - Volume 60 - Issue 5 - p e45–e46
doi: 10.1097/MPG.0000000000000233
Case Reports
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*Division of General Pediatrics

Division of Pathology, Saitama Children's Medical Center, Iwatsuki-ku, Saitama, Japan.

Address correspondence and reprint requests to Shin-Ichiro Hagiwara, Division of General Pediatrics, Saitama Children's Medical Center, 2100 Magome, Iwatsuki-ku, Saitama 339-8551, Japan (e-mail: hagiwara.shinichiro@pref.saitama.lg.jp).

Received 27 October, 2013

Accepted 27 October, 2013

The authors report no potential conflicts of interests.

Peliosis hepatis (PH) is a rare condition of unknown pathogenesis, presenting with multiple cystic blood-filled spaces throughout the liver and spleen parenchyma. PH is usually associated with chronic pathological conditions, such as tuberculosis, cystic fibrosis, human immunodeficiency virus infection, and prolonged use of medications, including anabolic steroids.

In children, several cases of PH with X-linked myotubular myopathy (XLMTM) have been reported (1,2). XLMTM is a congenital myopathy characterized by the presence of central nuclei in biopsy specimens from affected male subjects (3).

We report a case of a 2-year 4-month-old boy with known XLMTM who was hospitalized for pneumonia. He died from hypovolemic shock on day 4 of hospitalization. Autopsy revealed intraperitoneal hemorrhage from PH. We obtained the patients’ consent for this case report.

A 2-year 4-month-old boy with XLMTM was referred to our tertiary care medical center for pyrexia with cough. He was born at 39 weeks’ gestation via normal vaginal delivery. Severe hypotonia was present at birth and resuscitation was required. He had delayed motor milestones and was hospitalized several times for aspiration pneumonia. At 1 year, an open muscle biopsy confirmed a neuromuscular disorder. Skeletal muscle histopathology showed centrally placed nuclei surrounded by a perinuclear halo devoid of myofilaments, which strongly suspects XLMTM. Mutations (c. 614C>T) in the myotubularin (MTM1) gene were detected and XLMTM was diagnosed. Fever and wet cough began a day before admission and he was referred to the General Pediatrics Division at Saitama Children's Hospital. On admission, he was alert with a temperature of 38.5°C, blood pressure 94/67 mmHg, pulse 153 beats/min, respiratory rate 60 breaths/min, and oxygen saturation 90% in room air. Breath sound was diminished in the left lower lung field, and retractive breathing was present. Laboratory values on admission were as follows: white blood cell count 14,000/μL with 86.4% neutrophils, hemoglobin level 12.0 g/dL, platelet count 370,000/mm3, C-reactive protein level 0.05 mg/dL, aspartate transaminase level 92 IU/L, alanine transaminase level 72 IU/L, and total bilirubin level 0.2 mg/dL. The chest radiograph showed infiltration in the left lower lobe, and pneumonia was diagnosed.

After admission, intravenous fluids and antibiotics were administered and he was ventilated with bilevel positive airway pressure all day. On day 2, he was afebrile, and his respiratory condition improved. On the morning of day 4, his vital signs were normal, but laboratory values indicated anemia with a hemoglobin level of 9.3 g/dL, thrombopenia with a platelet count of 39,000/mm3, and elevated aspartate transaminase and alanine transaminase levels of 707 and 343 IU/L, respectively. Blood clotting was normal. On the evening of day 4, he suffered a cardiopulmonary arrest after sudden profound decreased oxygen saturation and bradycardia. Resuscitation was unsuccessful. Autopsy revealed the presence of bloody ascetic fluid (650 mL) in the abdominal cavity along with a ruptured capsule of the right lobe and a subcapsular hematoma enclosing the inferior surface of this lobe. The resected liver section showed parenchyma disrupted by blood-filled spaces up to 8 mm in diameter (Fig. 1). Histologically, sinusoidal ectasia and numerous tiny blood-filled spaces with no CD31 expression were diffusely distributed in both lobes (Fig. 2). PH was diagnosed from the macroscopic and histological findings. The cause of death was hemorrhagic shock as a result of intraperitoneal bleeding from PH.

FIGURE 1

FIGURE 1

FIGURE 2

FIGURE 2

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DISCUSSION

PH is a rare liver disease, with multiple blood-filled cystic spaces distributed throughout the liver parenchyma. It was first recognized by Wagner in 1861 and named by Schoenlank. Blood-filled cavities are caused by cystic dilation of the space of Disse or sinusoidal lumen. In children, PH has mostly been reported in combination with underlying chronic conditions, including cystic fibrosis, Fanconi anemia, malnutrition, congenital cardiopathy, Marfan syndrome, and myotubular myopathy (3), or after transplantation. Only 4 cases of PH without any underlying pathological condition have been reported (4). Clinical manifestations of PH vary, and range from asymptomatic cases to fatal outcomes owing to complications of liver cirrhosis or rupture and PH. This patient was asymptomatic, but showed persistent mild elevation of liver enzyme levels. Prevalence of PH in association with XLMTM is unclear. In a recent series of 55 patients with XLMTM, 6 had transient or persistent elevations in serum aminotransferases suggestive of hepatic dysfunction and 2 were found to have PH at autopsy (1). In Japan, the National Center of Neurology and Psychiatry reported 6 of 7 patients with XLMTM and liver complications: 1 hepatic hemorrhage, 1 low-density area of the liver and sudden death, 1 hepatic enlargement, 1 intrahepatic bile duct dilatation, and 2 elevated serum aminotransferase levels. These data suggest that the prevalence of PH in XLMTM is high. There is no specific treatment for PH, and approaches range from symptomatic treatment to liver transplantation (5). The indication for liver transplantation for PH in the patients with XLMTM should be discussed in view of XLMTM prognosis. Terlizzi et al (6) report the first case of PH with XLMTM who was successfully treated with angiography and hepatic artery embolization without the need for operative intervention. This treatment strategy may be the first choice for PH with XLMTM. The association between XLMTM and PH is unclear. In this case, the liver and hepatic capsule were very fragile at autopsy. Mutations in MTM1 encoding myotubularin cause XLMTM. MTM1 belongs to a large family of dual-specificity phosphatases that play a role in the epigenetic regulation of signaling pathways involved in growth and differentiation (7).

Hnia et al (8) reported that MTM1 is a major regulator of both the desmin cytoskeleton and mitochondria homeostasis, specifically in skeletal muscles. Defects in intermediate filament stabilization and mitochondrial dynamics are common physiopathological features of myotubular and desmin-related myopathies. Desmin is also expressed in the liver, especially in hepatic stellate cells within the liver sinusoids (9).

Here, desmin-positive cells were only detected in the walls of the liver vessels and not within the sinusoids of the liver parenchyma (Fig. 3), which may be a clue as to why PH is likely to occur in association with XLMTM.

FIGURE 3

FIGURE 3

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CONCLUSIONS

Myotubular myopathy may not be simply a muscle disease, but also a systemic disease affecting the liver. We recommend that all patients with XLMTM undergo routine liver function testing and abdominal ultrasonography even if they are asymptomatic.

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REFERENCES

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