Rheumatology Advance Access originally published online on February 16, 2007
Rheumatology 2007 46(4):720-721; doi:10.1093/rheumatology/kem011
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Neonatal antiphospholipid syndrome associated with heterozygous methylentetrahydrofolate reductase C677T and prothrombin G20210A gene mutations
inUniversity Children's Hospital Ljubljana, Ljubljana, Slovenia
Correspondence to: T. Avin. E-mail: tadej.avcin{at}kclj.si
SIR, Neonatal antiphospholipid syndrome (APS) is a rare clinical entity characterized by neonatal thrombotic disease due to the transplacental passage of maternal antiphospholipid antibodies (aPL) [1]. While women with aPL show a high incidence of obstetric and fetal complications, the aPL-related thrombosis in their offspring seems to be exceedingly rare. The low frequency of neonatal thrombosis has been attributed to the lack of the most known ‘second hit’ risk factors in infants, and to a low transplacental passage of IgG2 subclass of aPL, which are responsible for most clinical pathogenicity [2]. We describe a neonate who developed ischaemic stroke in the left middle cerebral artery and was found to have positive aPL together with two underlying inherited prothrombotic disorders.
The girl was born to healthy, unrelated parents after the first uncomplicated pregnancy at 40 weeks of gestation. Maternal grandfather had leg thrombosis and died of heart infarction and maternal uncle suffered perinatal intracranial haemorrhage. The delivery was uneventful except for meconium in amniotic fluid. The girl weighted 3280 g (P50), was 50 cm long (P50), had head circumference of 35 cm (P50) and Apgar score 9/9. At the age of 13 h she developed convulsions, which were stopped by phenobarbitone. Diagnostic workup revealed normal blood count, glucose and electrolytes. She had no laboratory signs of infection and blood culture remained sterile. An electroencephalogram was focally abnormal. Magnetic resonance imaging of the head showed ischaemic changes in the left hemisphere (Fig. 1A) and magnetic resonance angiography identified occlusion of the left-middle cerebral artery (Fig. 1B). Heart ultrasound demonstrated atrial septal defect type secundum.
|
The coagulation profile, which included prothrombin time, thrombin time, partial thromboplastin time, platelet count, fibrinogen, antithrombin III, protein S, protein C and lipoprotein, was normal. Molecular genetic testing demonstrated heterozygous methylentetrahydrofolate reductase C677T and prothrombin G20210A gene mutations. The G1691A factor V Leiden mutation was negative. Testing for aPL was performed 14 days after the delivery in the mother and showed very high levels of IgG anticardiolipin antibodies (>100 GPL), negative anti-ß2 glycoprotein I antibodies and negative lupus anticoagulant. Subsequently, we confirmed positive IgG anticardiolipin antibodies (24 GPL) also in the baby at the age of 7 weeks. She had no recurrence of seizures on therapy with phenobarbitone, but her neurological status remained abnormal with trunk hypotonia.
There is an increasing number of case reports describing neonates or infants who have suffered from thromboses associated with transplacentally acquired aPL [3–6]. Generally, it is believed that aPL per se are unable to induce thrombotic process in the intact neonatal vessel wall and it has been suggested that another thrombophilic factor, such as indwelling catheter, sepsis or prematurity may act as an initial trigger [3, 6]. Hereditary prothrombotic conditions, in particular methylentetrahydrofolate reductase C677T and prothrombin G20210A gene mutations, had not been routinely investigated in previous studies of neonatal APS. Our case report demonstrated for the first time concomitant presence of antiphospholipid antibodies and multiple prothrombotic gene mutations in a neonate with thrombosis. This finding further supports the multifactorial pathogenesis of neonatal APS and highlights the importance of thorough laboratory evaluation, including genetic testing of possible inherited prothrombotic abnormalities.
The authors have declared no conflicts of interest.
 |
References |
|---|
 Top References |
|---|
- Avin T, Cimaz R, Meroni PL. (2002) Recent advances in antiphospholipid antibodies and antiphospholipid syndromes in pediatric populations. Lupus 11:4–10.[Medline]
- Sammaritano LR, Ng S, Sobel R, et al. (1997) Anticardiolipin IgG subclasses: association of IgG2 with arterial and/or venous thrombosis. Arthritis Rheum 40:1998–2006.[Web of Science][Medline]
- Tabbutt S, Griswold WR, Ogino MT, Mendoza AE, Allen JB, Reznik VM. (1994) Multiple thromboses in a premature infant associated with maternal phospholipid antibody syndrome. J Perinatol 14:66–70.[Medline]
- Navarro F, Doña-Naranjo MA, Villanueva I. (1997) Neonatal Antiphospholipid Syndrome. J Rheumatol 24:1240–1.[Web of Science][Medline]
- de Klerk OL, de Vries TW, Sinnige LGF. (1999) An unusual cause of neonatal seizures in a newborn infant. Pediatrics 100:e8.
- Soares Rolim AM, Castro M, Santiago MB. (2006) Neonatal antiphospholipid syndrome. Lupus 15:301–3.
[Abstract/Free Full Text]
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  T. Avcin and E. Silverman Review: Antiphospholipid antibodies in pediatric systemic lupus erythematosus and the antiphospholipid syndrome Lupus, August 1, 2007; 16(8): 627 - 633. [Abstract] [PDF]
|
|
|
|
|
|
M.-C. Boffa and E. Lachassinne Review: Infant perinatal thrombosis and antiphospholipid antibodies: a review Lupus, August 1, 2007; 16(8): 634 - 641. [Abstract] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||