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Nemaline Myopathy in a Newborn Infant: a Rare Muscle Disorder Miopatia Nemalinowa U Noworodka – Opis Rzadkiej Choroby

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Nemaline Myopathy in a Newborn Infant: a Rare Muscle Disorder Miopatia Nemalinowa U Noworodka – Opis Rzadkiej Choroby View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Via Medica Journals CASE REPORT/OPIS PRZYPADKU Nemaline myopathy in a newborn infant: a rare muscle disorder Miopatia nemalinowa u noworodka – opis rzadkiej choroby Ozgur Olukman1, Sebnem Calkavur1, Gulden Diniz2, Aycan Unalp3, Fusun Atlihan1 1Department of Neonatology, Dr. Behçet Uz Children’s Hospital, Izmir, Turkey 2Department of Pathology, Dr. Behçet Uz Children’s Hospital, Izmir, Turkey 3Department of Pediatric Neurology, Dr. Behçet Uz Children’s Hospital, Izmir, Turkey Neurologia i Neurochirurgia Polska 2013; 47, 5: 493-498 DOI: 10.5114/ninp.2013.38229 A bstract Str eszc zenie Nemaline myopathy (NM) is a genetically and clinically het- Miopatia nemalinowa jest schorzeniem miêœni, niejednorod- erogeneous muscle disorder, defined by the presence of char- nym pod wzglêdem genetycznym i klinicznym. Chorobê acteristic nemaline bodies on muscle biopsy. The disease has cechuje obecnoœæ charakterystycznych struktur nemalino- a wide spectrum of phenotypes, ranging from forms with wych w bioptacie miêœnia. Fenotyp jest bardzo zró¿nicowa- neonatal onset and fatal outcome to asymptomatic forms. ny i obejmuje zarówno postacie noworodkowe prowadz¹ce The neonatal form is severe and usually fatal. The clinical do zgonu, jak i postacie bezobjawowe. Postaæ noworodkowa variability, with differing age of onset and severity of symp- przebiega ciê¿ko i zwykle koñczy siê œmierci¹. Zmiennoœæ kli- toms makes the diagnosis difficult during infancy. There is niczna, ³¹cznie ze zró¿nicowanym wiekiem w chwili wyst¹pie- no curative treatment. L-tyrosine may prevent aspiration by nia objawów i z ró¿nym ich nasileniem, mo¿e utrudniaæ roz- reducing pharyngeal secretions and drooling. Most of the poznanie w wieku niemowlêcym. Choroba jest nieuleczalna. patients die from respiratory and cardiac failure. Podawanie L-tyrozyny mo¿e zapobiec zach³yœniêciu poprzez This article discusses a newborn infant who presented with zmniejszenie produkcji wydzieliny w gardle i œliny. Wiêk- generalized weakness and respiratory failure. Partial respon- szoœæ chorych umiera z powodu niewydolnoœci oddechowej se to L-tyrosine treatment was noted. The case is worth pre- i kr¹¿enia. senting to remind clinicians of congenital myopathies in the W artykule omówiono przypadek noworodka z uogólnionym differential diagnosis of floppy infant during neonatal period niedow³adem i niewydolnoœci¹ oddechow¹. Reakcja na poda- and to emphasize the importance of muscle biopsy in dia- wanie L-tyrozyny by³a czêœciowa. Przedstawiony opis przy- gnosis. padku ma na celu przypomnienie klinicystom o miopatiach wrodzonych, które nale¿y uwzglêdniaæ w rozpoznaniu ró¿nico- Key words: congenital, myopathy, nemaline body, floppy, wym zespo³u wiotkiego dziecka w okresie noworodkowym, infant. oraz podkreœlenie znaczenia biopsji miêœnia w ustalaniu roz- poznania. S³owa kluczowe: wrodzona, miopatia, struktury ne malinowe, wiotkie, niemowlê. Correspondence address: Ozgur Olukman, MD, Dr. Behçet Uz Children’s Hospital, Department of Neonatology, 1374 sk. no: 11, Alsancak, 35220 Izmir, Turkey, e-mail: [email protected] Received: 30.07.2012; accepted: 23.01.2013 Neurologia i Neurochirurgia Polska 2013; 47, 5 493 Ozgur Olukman, Sebnem Calkavur, Gulden Diniz, Aycan Unalp, Fusun Atlihan Introduction after the 32nd week of pregnancy. At 36 weeks vaginal delivery had to be induced because of the onset of mem- Nemaline myopathy (NM) is a rare and heteroge- bra rupture and fetal distress. nous form of congenital myopathy which usually pre- Although the mother had not received any medica- sents in infancy or early childhood with hypotonia, slow- tion before or during delivery, the neonate had general- ly progressive weakness of the facial, bulbar, proximal ized hypotonia, severe dyspnea, bradycardia and central limb and respiratory muscles, lax ligaments, areflexia cyanosis at birth. The Apgar scores at 1 and 5 minutes and skeletal deformities. Bulbar dysfunction causes swal- were 2 and 6, respectively. He required immediate face lowing difficulties and drooling, and may predispose to mask/bag resuscitation in the delivery room. On admis- aspiration of oral secretions [1]. sion to our NICU, weak chest and diaphragmatic move- The clinical variability, with differing age of onset ments, central cyanosis and generalized muscle weak- and severity of symptoms makes the diagnosis difficult ness were identified. The infant lied in a frog-like in some cases [2]. Up till now, six different forms have position with abduction of the hips and an abnormal been described [3]. Type of inheritance may be autoso- extension of the limbs. When pulled to sitting position, mal dominant, autosomal recessive and X-linked dom- there was a remarkable head lag. In vertical suspension inant. his arms and legs were extended and on horizontal sus- Muscle enzymes are usually normal, but may be mild- pension his head and limbs hung loosely. Except his eye ly elevated in some cases. Electromyography (EMG) is movements, he did not have any spontaneous move- nonspecific. Muscle imaging is useful in distinguishing ments. Deep tendon reflexes were absent and neonatal between neuropathic and myopathic processes. Muscle reflexes including sucking and swallowing were biopsy is diagnostic. Biopsy specimens show numerous decreased. No abnormal primitive reflex could be detect- threads like inclusions on modified Gomori trichrome ed. Assessment of sensation did not reveal any patholo- staining [4]. gy. He did not have any dysmorphic features or con- Treatment is supportive. L-tyrosine may prevent genital defects. His karyotype was 46, XY. Widespread aspiration by reducing pharyngeal secretions and drool- fine crackles were auscultated over both lungs. Because ing [5]. Pneumonia due to aspiration occurs frequent- of severe respiratory failure, an endotracheal tube was ly. Most of the patients die from respiratory and cardiac placed and he was started on mechanical ventilation. failure during infancy. Chest radiography revealed bilateral reticulogranular Here we report a newborn baby who was admitted pattern and decreased lung ventilation. His blood gas- to our neonatal intensive care unit (NICU) with severe es were compatible with respiratory acidosis. He received respiratory failure and generalized muscle weakness and single dose of surfactant and he was started on dual diagnosed as NM on muscle biopsy. The case was found antibiotherapy with ampicillin and netilmicin. Routine worth presenting in order to remind clinicians of neona- haematological and biochemical examinations were com- tal muscle disorders in the differential diagnosis of severe pletely normal. Serial transfontanel ultrasonographic examinations performed in consideration of birth hypotonia during neonatal period. asphyxia on the first, third, seventh and fourteenth days of life were assessed to be normal. No pathology could Case report be seen on his electroencephalographic examination either. Echocardiography revealed restrictive patent duc- A newborn baby who was born from the first preg- tus arteriosus, patent foramen ovale and mild pulmonary nancy of a 29-year-old mother by vaginal delivery on hypertension. Because of his ongoing severe hypotonia, the 36th gestational week was admitted to our NICU weak cry and no effort to breath, muscle enzymes and because of severe respiratory failure soon after birth. His screening tests for congenital metabolic disorders were family history did not reveal any significance in terms performed and they were found to be completely nor- of neuromuscular disesases and there was no consan- mal. EMG or cerebrospinal magnetic resonance imag- guinity between his parents. His antenatal screening tests ing (MRI) could not be performed because of his were normal. However, fetal movements in the third dependency on mechanical ventilation. Eventually, in trimester of pregnancy felt by his mother and observed order to exclude congenital neuromuscular disorders, by the obstetrician on the fetal ultrasonography were a muscle biopsy was performed from gastrocnemius at decreased and marked polyhydramnios had emerged age 8 weeks and the diagnosis of NM was established. 494 Neurologia i Neurochirurgia Polska 2013; 47, 5 Nemaline myopathy in a newborn Microscopic examination revealed the intracellular accu- mulation of thread-like structures. The rods were not visible on hematoxylin-eosin staining, but appeared as red or purple structures against the blue-green myofib- rillar background with the modified Gomori trichrome stain (Fig. 1). The distribution of rods within myofibers showed a tendency to cluster around nuclei. Further- more an increased oxidative enzyme activity with cytochrome oxidase enzyme stain was also demonstrat- ed (Fig. 2). Immunohistochemical stainings were done by streptavidin-biotin immunoperoxidase complex me- thod using antibody against sarcomeric actin, smooth muscle actin, desmin and vimentin. Only focal desmin positivity could be demonstrated on these rods (Fig. 3). There was diffuse positivity in all muscle fibers with the Fig. 1. Modified Gomori trichrome stain showed characteristic purple-colored antibody against myosin heavy chain neonatal. Genetic rods in the perinuclear region analysis for specific gene mutations could not be per- formed. Diagnosis was based on clinical findings and the observation of characteristic rod-shaped structures (nemaline bodies) on muscle biopsy. Although he had received daily physiotherapy, he developed generalized
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