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644
Y Nagaoka et al.
Severe posterior reversible encephalopathy syndrome resolved with craniectomy Yoshinobu Nagaoka,1 Kenji Ishikura,1 Riku Hamada,1 Tadashi Miyagawa,2 Tatsuo Kono,3 Tomoyuki Sakai,1 Yuko Hamasaki,4 Hiroshi Hataya1 and Masataka Honda1 Departments of 1Nephrology, 2Neurosurgery, 3Radiology, Tokyo Metropolitan Children’s Medical Center and 4Department of Pediatric Nephrology, Toho University Omori Medical Center, Tokyo, Japan Abstract
Posterior reversible encephalopathy syndrome (PRES) has been thought to be a benign disease, but recently severe cases have been reported with increasing recognition. A 3-year-old girl with congenital nephrotic syndrome had rapidly progressed to coma. Computed tomography (CT) of the head showed striking swelling of the brainstem and transtentorial herniation. Emergency decompressive craniectomy was performed. Consecutively, blood pressure was optimally controlled. The patient gradually recovered to the previous state before onset of PRES. Rapid improvement of clinical symptoms and rapid resolution of abnormal findings on serial CT led to diagnosis of PRES. In severe PRES with unstable vital signs, surgical intervention should be considered as well as appropriate blood pressure management.
Key words brainstem, cerebellar herniation, decompressive craniectomy, reversible posterior leukoencephalopathy syndrome.
Posterior reversible encephalopathy syndrome (PRES) is a clinical neuroradiographic syndrome characterized by headache, altered consciousness, visual disturbances, and seizures, as well as predominantly posterior leukoencephalopathy on imaging.1,2 The nomenclature is not completely accurate: the syndrome is not always reversible, and it is often not confined to the posterior region of the brain.3–8 Several medical conditions have been implicated as causes of PRES, which have been recently described in the field of pediatric nephrology.2–5,9 The prognosis is usually benign, but delay in diagnosis and treatment may lead to permanent neurological sequelae.3–8 Particularly in cases of the brainstem variant of PRES, rapid treatment is required because deaths have been reported.4–6 Certainly, distinction between PRES and ischemic stroke is difficult, but it is important because the treatment of hypertension may differ in each condition.7,10 To achieve this, diffusionweighted imaging (DWI) and apparent diffusion coefficient (ADC) maps are helpful to differentiate PRES from early cerebral ischemia.4,7 In a serious case, however, it is difficult to carry out magnetic resonance imaging (MRI) during the unstable acute stage. Here we present the case of a 3-year-old girl with severe PRES who was diagnosed based on symptoms and serial computed tomography (CT) in the acute phase and rescued by emergency external decompression and ventricular drainage.
Correspondence: Kenji Ishikura, MD, PhD, Department of Nephrology, Tokyo Metropolitan Children’s Medical Center, 2-8-29 Musashidai, Fuchu, Tokyo 183-8561, Japan. Email: [email protected] Received 9 October 2012; revised 13 December 2012; accepted 8 February 2013. doi: 10.1111/ped.12084
© 2013 The Authors Pediatrics International © 2013 Japan Pediatric Society
Case report A 3-year-old girl was referred to Tokyo Metropolitan Children’s Medical Center from a local hospital and was prepared for peritoneal dialysis. She was diagnosed as having congenital nephrotic syndrome at birth because of huge placenta (36.7% of birthweight), oligohydramnios, proteinuria, and hypoalbuminemia. Genetic analysis of the NPHS1 gene indicated compound heterozygote mutation. Renal dysfunction had progressed rapidly since the age of 3, and urgent hemodialysis was performed. After stabilization, the patient was referred to Tokyo Metropolitan Children’s Medical Center and soon developed sepsis from catheter infection, which resulted in spastic paralysis. Three months after successful treatment of sepsis, peritoneal dialysis was initiated. On the day of the first episode, the patient suddenly complained of vomiting and restlessness, and then developed impaired consciousness. Clinical examination indicated pale face, muscular hypotonia, loss of light reflex, gasping respiration, decrease in respiratory rate, sinus bradycardia, and high blood pressure (155/108 mmHg). Convulsion was not observed, but consciousness was becoming unclear. Because hypertensive encephalopathy or epileptic seizures were suspected, i.v. midazolam was started promptly. Laboratory findings at this time were as follows: serum creatinine, 4.51 mg/dL; albumin, 2.6 g/ dL; sodium, 139 mEq/L; activated partial thromboplastin time, 20.8 s; and blood sugar, 350 mg/dL. Non-contrast brain CT obtained 1 h after the episode indicated striking swelling of the brainstem, cerebellum, and occipital lobe of the cerebrum, with multiple low-density areas, causing hydrocephalus, and upward transtentorial herniation (Fig. 1). Emergency decompressive craniectomy of the posterior fossa and ventricular drainage were performed, and then intensive care was started including mechanical ventilation, intracranial pressure
Severe brainstem variant of PRES
a
645
b
Fig. 1 Neuroimaging of a 3-year-old girl with severe posterior reversible encephalopathy syndrome. Computed tomography in (a) axial view and (b) reconstructed sagittal view at onset. The brainstem and cerebellum appeared strikingly swollen with upward transtentorial herniation. Low densities were apparent in periventricular deep white matter.
control, and sedative therapy for management of blood pressure (midazolam, morphine). Re-examination via CT after the operation showed multiple cerebral petechial hemorrhages inconsistent with vascular territories. Appropriate intracranial pressure control and supportive care resolved the general condition dramatically. T2-weighted and fluid-attenuated inversion recovery brain MRI on postoperative day 8 showed high-intensity areas in the corresponding areas of the postoperative CT images. In contrast, cerebellar lesion detected on CT was not seen on MRI (Fig. 2). With this clinical course and neuroimaging, severe PRES complicated with intracranial hemorrhages and brainstem edema was diagnosed. Drainage was removed and withdrawal of the respirator were achieved on postoperative days 11 and 18, respectively. Two months after the episode, intermittent vomiting and febrile seizure were observed. Blood pressure was 150/ 125 mmHg. Although excess fluid was not given, chronic fluid retention became clear later (human atrial natriuretic peptide, 113 pg/mL). CT of the brain indicated extended low-density areas mainly in the left parietal lobe and parenchymal hemorrhages. Given a diagnosis of recurrent PRES, sedative and antihypertensive medication (nifedipine, nicardipine, and lisinopril) were provided successfully. Follow-up CT showed improvement of brain swelling. Now at the age of 4, the patient is seizure-free under anticonvulsant medication and maintaining the same state as before onset of PRES.
before.3–8 If PRES is not promptly and appropriately treated, the disease condition is progressive and fatal. Namely, reversible effects such as capillary leak (vasogenic edema) or petechial hemorrhage may develop into irreversible widespread hemorrhage due to breaking down of endothelial function.5,10 As well as broad intracranial hemorrhage, posterior fossa lesion such as PRES brainstem variant can lead to mortality. This is because the marked mass effect could lead to effacement of the herniation and sudden deterioration in neurological status.5,9 In the present case,
Discussion We herein report the case of a 3-year-old girl with severe PRES resolved by emergency decompressive craniectomy for increased intracranial pressure and brain herniation. Although MRI was not able to be obtained in the acute phase, the patient was diagnosed with PRES from symptoms and serial brain CT findings: multiple lesions inconsistent with vascular territories and recovery of the density changes. To our knowledge, this is the first resolved case of very severe PRES by decompressive craniectomy. Recently, PRES with severe clinical course has been reported because it is now better recognized in clinical practice than
Fig. 2 Magnetic resonance imaging at postoperative day 8: axial view on T2-weighted sequence. Brain swelling was obviously decreased compared with the CT findings. There were no suggestive findings of infarction. © 2013 The Authors Pediatrics International © 2013 Japan Pediatric Society
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646 Y Nagaoka et al. rapid decompressive treatment including craniectomy, drainage and suitable blood pressure management saved the patient’s life. Although MRI of the head is the gold standard of imaging for detecting PRES lesions, MRI cannot be obtained under highly unstable conditions as in the present case. It is generally agreed that early phase PRES abnormalities are delineated with greater clarity on MRI than CT. Meanwhile, CT is useful to detect hemorrhages that are common in severe PRES,3,5,6 and enables the evaluation of marked edema in the posterior fossa.5,6,9 We regard that CT in the acute phase of PRES is a practical option. In the present patient, known risk factors for PRES included high blood pressure and renal dysfunction. There were no predisposing causes that explained acute elevation of blood pressure, but it is possible that hypertension resulted from PRES (Cushing phenomenon due to brain herniation). Otherwise, kidney dysfunction is one of the significant risk factors, as in previous reports.2,7 Additional factors of potential importance were infection and sepsis, which contributed to underlying microvascular vulnerability.7,8Given that the patient had been undergoing peritoneal dialysis and was in the recovery phase of septic shock, the remaining endothelial damage might have led to capillary leak and consequent severe PRES. Conclusion
Brainstem variant of PRES can progress to brain herniation and threaten the patient’s life. Correct diagnosis should be made and treatment should not be delayed. It is important that clinicians are alert to the possibility of this diagnosis, and recognize the condition early so that control of blood pressure, even decompressive surgical intervention, can be instituted quickly to prevent permanent brain damage.
Acknowledgment We thank Dr Tomohide Goto, Department of Neurology, for valuable advice on clinical management.
References 1 Hinchey J, Chaves C, Appignani B et al. A reversible posterior leukoencephalopathy syndrome. N. Engl. J. Med. 1996; 334: 494– 500. 2 Ishikura K, Hamasaki Y, Sakai T, Hataya H, Mak RH, Honda M. Posterior reversible encephalopathy syndrome in children with kidney diseases. Pediatr. Nephrol. 2012; 27: 375–84. 3 Schwartz RB, Bravo SM, Klufas RA et al. Cyclosporine neurotoxicity and its relationship to hypertensive encephalopathy: CT and MR findings in 16 cases. AJR Am. J. Roentgenol. 1995; 165: 627–31. 4 Covarrubias DJ, Luetmer PH, Campeau NG. Posterior reversible encephalopathy syndrome: Prognostic utility of quantitative diffusion-weighted MR images. AJNR Am. J. Neuroradiol. 2002; 23: 1038–48. 5 Kheir JN, Lawlor MW, Ahn ES et al. Neuropathology of a fatal case of posterior reversible encephalopathy syndrome. Pediatr. Dev. Pathol. 2010; 13: 397–403. 6 Weingarten K, Barbut D, Filippi C, Zimmerman RD. Acute hypertensive encephalopathy: Findings on spin-echo and gradient-echo MR imaging. AJR Am. J. Roentgenol. 1994; 162: 665–70. 7 Ay H, Buonanno FS, Schaefer PW et al. Posterior leukoencephalopathy without severe hypertension: Utility of diffusion-weighted MRI. Neurology 1998; 51: 1369–76. 8 Bartynski WS, Boardman JF, Zeigler ZR, Shadduck RK, Lister J. Posterior reversible encephalopathy syndrome in infection, sepsis, and shock. AJNR Am. J. Neuroradiol. 2006; 27: 2179–90. 9 Keyserling HF, Provenzale JM. Atypical imaging findings in a near-fatal case of posterior reversible encephalopathy syndrome in a child. AJR Am. J. Roentgenol. 2007; 188: 219–21. 10 Vaughan CJ, Delanty N. Hypertensive emergencies. Lancet 2000; 356: 411–17.
Childhood-onset hereditary pancreatitis with mutations in the CT gene and SPINK1 gene Hiroyuki Awano,1 Tomoko Lee,1 Mariko Yagi,1 Atsushi Masamune,2 Kiyoshi Kume,2 Yasuhiro Takeshima1 and Kazumoto Iijima1 1 Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe and 2Department of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan Abstract
Hereditary pancreatitis (HP) is an autosomal-dominant gene disorder. The affected genes have been identified as the cationic trypsinogen (CT) gene and the serine protease inhibitor Kazal type 1 (SPINK1) gene. These gene abnormalities alone, however, do not necessarily regulate the onset or severity of pancreatitis, suggesting the involvement of other gene abnormalities and environmental factors. Reported herein is the case of a 9-year-old boy with early-onset HP due to mutations in the CT and SPINK1 genes. The patient had a p.R122H heterozygous mutation in the CT gene and a p.N34S
Correspondence: Hiroyuki Awano, PhD, Department of Pediatrics, Kobe University Graduate School of Medicine, 7-5-1 Kusunokicho, Chuo, Kobe 650-0017, Japan. Email: [email protected] Received 19 August 2012; revised 13 December 2012; accepted 8 February 2013. doi: 10.1111/ped.12152
© 2013 The Authors Pediatrics International © 2013 Japan Pediatric Society
644
Y Nagaoka et al.
Severe posterior reversible encephalopathy syndrome resolved with craniectomy Yoshinobu Nagaoka,1 Kenji Ishikura,1 Riku Hamada,1 Tadashi Miyagawa,2 Tatsuo Kono,3 Tomoyuki Sakai,1 Yuko Hamasaki,4 Hiroshi Hataya1 and Masataka Honda1 Departments of 1Nephrology, 2Neurosurgery, 3Radiology, Tokyo Metropolitan Children’s Medical Center and 4Department of Pediatric Nephrology, Toho University Omori Medical Center, Tokyo, Japan Abstract
Posterior reversible encephalopathy syndrome (PRES) has been thought to be a benign disease, but recently severe cases have been reported with increasing recognition. A 3-year-old girl with congenital nephrotic syndrome had rapidly progressed to coma. Computed tomography (CT) of the head showed striking swelling of the brainstem and transtentorial herniation. Emergency decompressive craniectomy was performed. Consecutively, blood pressure was optimally controlled. The patient gradually recovered to the previous state before onset of PRES. Rapid improvement of clinical symptoms and rapid resolution of abnormal findings on serial CT led to diagnosis of PRES. In severe PRES with unstable vital signs, surgical intervention should be considered as well as appropriate blood pressure management.
Key words brainstem, cerebellar herniation, decompressive craniectomy, reversible posterior leukoencephalopathy syndrome.
Posterior reversible encephalopathy syndrome (PRES) is a clinical neuroradiographic syndrome characterized by headache, altered consciousness, visual disturbances, and seizures, as well as predominantly posterior leukoencephalopathy on imaging.1,2 The nomenclature is not completely accurate: the syndrome is not always reversible, and it is often not confined to the posterior region of the brain.3–8 Several medical conditions have been implicated as causes of PRES, which have been recently described in the field of pediatric nephrology.2–5,9 The prognosis is usually benign, but delay in diagnosis and treatment may lead to permanent neurological sequelae.3–8 Particularly in cases of the brainstem variant of PRES, rapid treatment is required because deaths have been reported.4–6 Certainly, distinction between PRES and ischemic stroke is difficult, but it is important because the treatment of hypertension may differ in each condition.7,10 To achieve this, diffusionweighted imaging (DWI) and apparent diffusion coefficient (ADC) maps are helpful to differentiate PRES from early cerebral ischemia.4,7 In a serious case, however, it is difficult to carry out magnetic resonance imaging (MRI) during the unstable acute stage. Here we present the case of a 3-year-old girl with severe PRES who was diagnosed based on symptoms and serial computed tomography (CT) in the acute phase and rescued by emergency external decompression and ventricular drainage.
Correspondence: Kenji Ishikura, MD, PhD, Department of Nephrology, Tokyo Metropolitan Children’s Medical Center, 2-8-29 Musashidai, Fuchu, Tokyo 183-8561, Japan. Email: [email protected] Received 9 October 2012; revised 13 December 2012; accepted 8 February 2013. doi: 10.1111/ped.12084
© 2013 The Authors Pediatrics International © 2013 Japan Pediatric Society
Case report A 3-year-old girl was referred to Tokyo Metropolitan Children’s Medical Center from a local hospital and was prepared for peritoneal dialysis. She was diagnosed as having congenital nephrotic syndrome at birth because of huge placenta (36.7% of birthweight), oligohydramnios, proteinuria, and hypoalbuminemia. Genetic analysis of the NPHS1 gene indicated compound heterozygote mutation. Renal dysfunction had progressed rapidly since the age of 3, and urgent hemodialysis was performed. After stabilization, the patient was referred to Tokyo Metropolitan Children’s Medical Center and soon developed sepsis from catheter infection, which resulted in spastic paralysis. Three months after successful treatment of sepsis, peritoneal dialysis was initiated. On the day of the first episode, the patient suddenly complained of vomiting and restlessness, and then developed impaired consciousness. Clinical examination indicated pale face, muscular hypotonia, loss of light reflex, gasping respiration, decrease in respiratory rate, sinus bradycardia, and high blood pressure (155/108 mmHg). Convulsion was not observed, but consciousness was becoming unclear. Because hypertensive encephalopathy or epileptic seizures were suspected, i.v. midazolam was started promptly. Laboratory findings at this time were as follows: serum creatinine, 4.51 mg/dL; albumin, 2.6 g/ dL; sodium, 139 mEq/L; activated partial thromboplastin time, 20.8 s; and blood sugar, 350 mg/dL. Non-contrast brain CT obtained 1 h after the episode indicated striking swelling of the brainstem, cerebellum, and occipital lobe of the cerebrum, with multiple low-density areas, causing hydrocephalus, and upward transtentorial herniation (Fig. 1). Emergency decompressive craniectomy of the posterior fossa and ventricular drainage were performed, and then intensive care was started including mechanical ventilation, intracranial pressure
Severe brainstem variant of PRES
a
645
b
Fig. 1 Neuroimaging of a 3-year-old girl with severe posterior reversible encephalopathy syndrome. Computed tomography in (a) axial view and (b) reconstructed sagittal view at onset. The brainstem and cerebellum appeared strikingly swollen with upward transtentorial herniation. Low densities were apparent in periventricular deep white matter.
control, and sedative therapy for management of blood pressure (midazolam, morphine). Re-examination via CT after the operation showed multiple cerebral petechial hemorrhages inconsistent with vascular territories. Appropriate intracranial pressure control and supportive care resolved the general condition dramatically. T2-weighted and fluid-attenuated inversion recovery brain MRI on postoperative day 8 showed high-intensity areas in the corresponding areas of the postoperative CT images. In contrast, cerebellar lesion detected on CT was not seen on MRI (Fig. 2). With this clinical course and neuroimaging, severe PRES complicated with intracranial hemorrhages and brainstem edema was diagnosed. Drainage was removed and withdrawal of the respirator were achieved on postoperative days 11 and 18, respectively. Two months after the episode, intermittent vomiting and febrile seizure were observed. Blood pressure was 150/ 125 mmHg. Although excess fluid was not given, chronic fluid retention became clear later (human atrial natriuretic peptide, 113 pg/mL). CT of the brain indicated extended low-density areas mainly in the left parietal lobe and parenchymal hemorrhages. Given a diagnosis of recurrent PRES, sedative and antihypertensive medication (nifedipine, nicardipine, and lisinopril) were provided successfully. Follow-up CT showed improvement of brain swelling. Now at the age of 4, the patient is seizure-free under anticonvulsant medication and maintaining the same state as before onset of PRES.
before.3–8 If PRES is not promptly and appropriately treated, the disease condition is progressive and fatal. Namely, reversible effects such as capillary leak (vasogenic edema) or petechial hemorrhage may develop into irreversible widespread hemorrhage due to breaking down of endothelial function.5,10 As well as broad intracranial hemorrhage, posterior fossa lesion such as PRES brainstem variant can lead to mortality. This is because the marked mass effect could lead to effacement of the herniation and sudden deterioration in neurological status.5,9 In the present case,
Discussion We herein report the case of a 3-year-old girl with severe PRES resolved by emergency decompressive craniectomy for increased intracranial pressure and brain herniation. Although MRI was not able to be obtained in the acute phase, the patient was diagnosed with PRES from symptoms and serial brain CT findings: multiple lesions inconsistent with vascular territories and recovery of the density changes. To our knowledge, this is the first resolved case of very severe PRES by decompressive craniectomy. Recently, PRES with severe clinical course has been reported because it is now better recognized in clinical practice than
Fig. 2 Magnetic resonance imaging at postoperative day 8: axial view on T2-weighted sequence. Brain swelling was obviously decreased compared with the CT findings. There were no suggestive findings of infarction. © 2013 The Authors Pediatrics International © 2013 Japan Pediatric Society
bs_bs_banner
646 Y Nagaoka et al. rapid decompressive treatment including craniectomy, drainage and suitable blood pressure management saved the patient’s life. Although MRI of the head is the gold standard of imaging for detecting PRES lesions, MRI cannot be obtained under highly unstable conditions as in the present case. It is generally agreed that early phase PRES abnormalities are delineated with greater clarity on MRI than CT. Meanwhile, CT is useful to detect hemorrhages that are common in severe PRES,3,5,6 and enables the evaluation of marked edema in the posterior fossa.5,6,9 We regard that CT in the acute phase of PRES is a practical option. In the present patient, known risk factors for PRES included high blood pressure and renal dysfunction. There were no predisposing causes that explained acute elevation of blood pressure, but it is possible that hypertension resulted from PRES (Cushing phenomenon due to brain herniation). Otherwise, kidney dysfunction is one of the significant risk factors, as in previous reports.2,7 Additional factors of potential importance were infection and sepsis, which contributed to underlying microvascular vulnerability.7,8Given that the patient had been undergoing peritoneal dialysis and was in the recovery phase of septic shock, the remaining endothelial damage might have led to capillary leak and consequent severe PRES. Conclusion
Brainstem variant of PRES can progress to brain herniation and threaten the patient’s life. Correct diagnosis should be made and treatment should not be delayed. It is important that clinicians are alert to the possibility of this diagnosis, and recognize the condition early so that control of blood pressure, even decompressive surgical intervention, can be instituted quickly to prevent permanent brain damage.
Acknowledgment We thank Dr Tomohide Goto, Department of Neurology, for valuable advice on clinical management.
References 1 Hinchey J, Chaves C, Appignani B et al. A reversible posterior leukoencephalopathy syndrome. N. Engl. J. Med. 1996; 334: 494– 500. 2 Ishikura K, Hamasaki Y, Sakai T, Hataya H, Mak RH, Honda M. Posterior reversible encephalopathy syndrome in children with kidney diseases. Pediatr. Nephrol. 2012; 27: 375–84. 3 Schwartz RB, Bravo SM, Klufas RA et al. Cyclosporine neurotoxicity and its relationship to hypertensive encephalopathy: CT and MR findings in 16 cases. AJR Am. J. Roentgenol. 1995; 165: 627–31. 4 Covarrubias DJ, Luetmer PH, Campeau NG. Posterior reversible encephalopathy syndrome: Prognostic utility of quantitative diffusion-weighted MR images. AJNR Am. J. Neuroradiol. 2002; 23: 1038–48. 5 Kheir JN, Lawlor MW, Ahn ES et al. Neuropathology of a fatal case of posterior reversible encephalopathy syndrome. Pediatr. Dev. Pathol. 2010; 13: 397–403. 6 Weingarten K, Barbut D, Filippi C, Zimmerman RD. Acute hypertensive encephalopathy: Findings on spin-echo and gradient-echo MR imaging. AJR Am. J. Roentgenol. 1994; 162: 665–70. 7 Ay H, Buonanno FS, Schaefer PW et al. Posterior leukoencephalopathy without severe hypertension: Utility of diffusion-weighted MRI. Neurology 1998; 51: 1369–76. 8 Bartynski WS, Boardman JF, Zeigler ZR, Shadduck RK, Lister J. Posterior reversible encephalopathy syndrome in infection, sepsis, and shock. AJNR Am. J. Neuroradiol. 2006; 27: 2179–90. 9 Keyserling HF, Provenzale JM. Atypical imaging findings in a near-fatal case of posterior reversible encephalopathy syndrome in a child. AJR Am. J. Roentgenol. 2007; 188: 219–21. 10 Vaughan CJ, Delanty N. Hypertensive emergencies. Lancet 2000; 356: 411–17.
Childhood-onset hereditary pancreatitis with mutations in the CT gene and SPINK1 gene Hiroyuki Awano,1 Tomoko Lee,1 Mariko Yagi,1 Atsushi Masamune,2 Kiyoshi Kume,2 Yasuhiro Takeshima1 and Kazumoto Iijima1 1 Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe and 2Department of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan Abstract
Hereditary pancreatitis (HP) is an autosomal-dominant gene disorder. The affected genes have been identified as the cationic trypsinogen (CT) gene and the serine protease inhibitor Kazal type 1 (SPINK1) gene. These gene abnormalities alone, however, do not necessarily regulate the onset or severity of pancreatitis, suggesting the involvement of other gene abnormalities and environmental factors. Reported herein is the case of a 9-year-old boy with early-onset HP due to mutations in the CT and SPINK1 genes. The patient had a p.R122H heterozygous mutation in the CT gene and a p.N34S
Correspondence: Hiroyuki Awano, PhD, Department of Pediatrics, Kobe University Graduate School of Medicine, 7-5-1 Kusunokicho, Chuo, Kobe 650-0017, Japan. Email: [email protected] Received 19 August 2012; revised 13 December 2012; accepted 8 February 2013. doi: 10.1111/ped.12152
© 2013 The Authors Pediatrics International © 2013 Japan Pediatric Society
