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Zellweger spectrum disorders: clinical overview and management approach.

Klouwer FC, Berendse K, Ferdinandusse S, Wanders RJ, Engelen M, Poll-The BT - Orphanet J Rare Dis (2015)

Bottom Line: Patients can present in the neonatal period with severe symptoms or later in life during adolescence or adulthood with only minor features.A defect of functional peroxisomes results in several metabolic abnormalities, which in most cases can be detected in blood and urine.There is currently no curative therapy, but supportive care is available.

View Article: PubMed Central - PubMed

Affiliation: Department of Paediatric Neurology, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Meibergdreef 9, PO BOX 22660, 1105 AZ, Amsterdam, The Netherlands. f.c.klouwer@amc.uva.nl.

ABSTRACT
Zellweger spectrum disorders (ZSDs) represent the major subgroup within the peroxisomal biogenesis disorders caused by defects in PEX genes. The Zellweger spectrum is a clinical and biochemical continuum which can roughly be divided into three clinical phenotypes. Patients can present in the neonatal period with severe symptoms or later in life during adolescence or adulthood with only minor features. A defect of functional peroxisomes results in several metabolic abnormalities, which in most cases can be detected in blood and urine. There is currently no curative therapy, but supportive care is available. This review focuses on the management of patients with a ZSD and provides recommendations for supportive therapeutic options for all those involved in the care for ZSD patients.

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Related in: MedlinePlus

Craniofacial dysmorphic features in ZSD patients developing over time a. Photograph of a 6-month-old girl with typical craniofacial dysmorphia. Note the epicantal folds, high forehead, broad nasal bridge and hypoplastic supraorbital ridges. The anterior fontanel is drawn and enlarged. b-c. Girl with a ZSD at the age of 9 months (b) and at the age of 1 year and two months (c). Less pronounced facial dysmorphism is present: a high forehead is seen, a broad nasal bridge, hypoplastic supraorbital ridges, anteverted nares and more subtle epicantal folds. d-f. Photograph of a male with a ZSD at the age of 5 years (d), 10 years (e) and 15 years (f). No evident facial dysmorphic features can be recognized, although the ears seem to be slightly low-set. Written informed consent was obtained from the parents of all patients for publication of these images
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Fig2: Craniofacial dysmorphic features in ZSD patients developing over time a. Photograph of a 6-month-old girl with typical craniofacial dysmorphia. Note the epicantal folds, high forehead, broad nasal bridge and hypoplastic supraorbital ridges. The anterior fontanel is drawn and enlarged. b-c. Girl with a ZSD at the age of 9 months (b) and at the age of 1 year and two months (c). Less pronounced facial dysmorphism is present: a high forehead is seen, a broad nasal bridge, hypoplastic supraorbital ridges, anteverted nares and more subtle epicantal folds. d-f. Photograph of a male with a ZSD at the age of 5 years (d), 10 years (e) and 15 years (f). No evident facial dysmorphic features can be recognized, although the ears seem to be slightly low-set. Written informed consent was obtained from the parents of all patients for publication of these images

Mentions: ZSD patients within this group typically present in the neonatal period with hepatic dysfunction and profound hypotonia resulting in prolonged jaundice and feeding difficulties. Epileptic seizures are usually present in these patients. Characteristic dysmorphic features can usually be found, of which the facial dysmorphic signs are most evident (Fig. 2a). Sensorineural deafness and ocular abnormalities like retinopathy, cataracts and glaucoma are typical but not always recognized at first presentation. Brain magnetic resonance imaging (MRI) may show neocortical dysplasia (especially perisylvian polymicrogyria), generalized decrease in white matter volume, delayed myelination, bilaterial ventricular dilatation and germinolytic cysts [23]. Neonatal onset leukodystrophy is rarely described [25]. Calcific stippling (chondrodysplasia punctata) may be present, especially in the knees and hips. The neonatal-infantile presentation grossly resembles what was originally described as classic ZS. Prognosis is poor and survival is usually not beyond the first year of life.Fig. 2


Zellweger spectrum disorders: clinical overview and management approach.

Klouwer FC, Berendse K, Ferdinandusse S, Wanders RJ, Engelen M, Poll-The BT - Orphanet J Rare Dis (2015)

Craniofacial dysmorphic features in ZSD patients developing over time a. Photograph of a 6-month-old girl with typical craniofacial dysmorphia. Note the epicantal folds, high forehead, broad nasal bridge and hypoplastic supraorbital ridges. The anterior fontanel is drawn and enlarged. b-c. Girl with a ZSD at the age of 9 months (b) and at the age of 1 year and two months (c). Less pronounced facial dysmorphism is present: a high forehead is seen, a broad nasal bridge, hypoplastic supraorbital ridges, anteverted nares and more subtle epicantal folds. d-f. Photograph of a male with a ZSD at the age of 5 years (d), 10 years (e) and 15 years (f). No evident facial dysmorphic features can be recognized, although the ears seem to be slightly low-set. Written informed consent was obtained from the parents of all patients for publication of these images
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4666198&req=5

Fig2: Craniofacial dysmorphic features in ZSD patients developing over time a. Photograph of a 6-month-old girl with typical craniofacial dysmorphia. Note the epicantal folds, high forehead, broad nasal bridge and hypoplastic supraorbital ridges. The anterior fontanel is drawn and enlarged. b-c. Girl with a ZSD at the age of 9 months (b) and at the age of 1 year and two months (c). Less pronounced facial dysmorphism is present: a high forehead is seen, a broad nasal bridge, hypoplastic supraorbital ridges, anteverted nares and more subtle epicantal folds. d-f. Photograph of a male with a ZSD at the age of 5 years (d), 10 years (e) and 15 years (f). No evident facial dysmorphic features can be recognized, although the ears seem to be slightly low-set. Written informed consent was obtained from the parents of all patients for publication of these images
Mentions: ZSD patients within this group typically present in the neonatal period with hepatic dysfunction and profound hypotonia resulting in prolonged jaundice and feeding difficulties. Epileptic seizures are usually present in these patients. Characteristic dysmorphic features can usually be found, of which the facial dysmorphic signs are most evident (Fig. 2a). Sensorineural deafness and ocular abnormalities like retinopathy, cataracts and glaucoma are typical but not always recognized at first presentation. Brain magnetic resonance imaging (MRI) may show neocortical dysplasia (especially perisylvian polymicrogyria), generalized decrease in white matter volume, delayed myelination, bilaterial ventricular dilatation and germinolytic cysts [23]. Neonatal onset leukodystrophy is rarely described [25]. Calcific stippling (chondrodysplasia punctata) may be present, especially in the knees and hips. The neonatal-infantile presentation grossly resembles what was originally described as classic ZS. Prognosis is poor and survival is usually not beyond the first year of life.Fig. 2

Bottom Line: Patients can present in the neonatal period with severe symptoms or later in life during adolescence or adulthood with only minor features.A defect of functional peroxisomes results in several metabolic abnormalities, which in most cases can be detected in blood and urine.There is currently no curative therapy, but supportive care is available.

View Article: PubMed Central - PubMed

Affiliation: Department of Paediatric Neurology, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Meibergdreef 9, PO BOX 22660, 1105 AZ, Amsterdam, The Netherlands. f.c.klouwer@amc.uva.nl.

ABSTRACT
Zellweger spectrum disorders (ZSDs) represent the major subgroup within the peroxisomal biogenesis disorders caused by defects in PEX genes. The Zellweger spectrum is a clinical and biochemical continuum which can roughly be divided into three clinical phenotypes. Patients can present in the neonatal period with severe symptoms or later in life during adolescence or adulthood with only minor features. A defect of functional peroxisomes results in several metabolic abnormalities, which in most cases can be detected in blood and urine. There is currently no curative therapy, but supportive care is available. This review focuses on the management of patients with a ZSD and provides recommendations for supportive therapeutic options for all those involved in the care for ZSD patients.

Show MeSH
Related in: MedlinePlus