Abstract
Zellweger spectrum disorder (ZSD) is a heterogeneous group of autosomal recessive disorders characterized by a defect in peroxisome formation and attributable to mutations in the PEX gene family. Patients with ZSD have profound neurologic impairments, including seizures, severe retardation, and dysmorphic features, and poor prognosis. Currently, there is no specific, effective treatment. Here, we investigated the effects of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on PEX1-related ZSD. The suspected clinical proband was first diagnosed at the Department of Neurology of our hospital. The proband died soon after diagnosis, and his family was studied. We found that a brother had the same genetic alterations, and he was diagnosed with Infantile Refsum disease (IRD) as the mildest form of ZSD. We implemented treatment with allo-HSCT, at the request of the child's parents. After transplantation, we observed significant improvements in the clinical manifestations, very-long-chain fatty acids, and brain MRI. The patient has recovered well and not showed any abnormal clinical manifestations after 2 years of follow-up. We have achieved satisfactory short-term results in the treatment of ZSD-IRD with allo-HSCT. Long-term follow-up and observation will be performed to determine the long-term prognosis.
Highlights
Zellweger spectrum disorders (ZSD) is defined by a continuum of three phenotypes and the biochemical and molecular bases of these disorders have been fully determined and include severe (Zellweger syndrome) and milder phenotypes [neonatal adrenoleukodystrophy and infantile Refsum disease (IRD)] [1]
Allogeneic hematopoietic stem cell transplantation is an effective method to treat X-linked adrenoleukodystrophy (X-ALD) in childhood [6], but there is no report about HSCT in ZSD patients
After several rounds of discussion, the MDT team reached the consensus that HSCT might be beneficial to a subgroup of patients with ZSD
Summary
Zellweger spectrum disorders (ZSD) is defined by a continuum of three phenotypes and the biochemical and molecular bases of these disorders have been fully determined and include severe (Zellweger syndrome) and milder phenotypes [neonatal adrenoleukodystrophy and infantile Refsum disease (IRD)] [1]. Severe ZSD manifestations include neurological impairments, stunting, and multiple congenital abnormalities involving the brain, bone, liver, eyes, kidneys, and endocrine. Intermediate/milder ZSD have no congenital malformations, but rather progressive peroxisome dysfunction variably manifests with sensory loss and neurologic involvement (ataxia, polyneuropathy, and leukodystrophy). This study mainly involved a pair of brothers with PEX1related ZSD They were diagnosed with ZSD-IRD with clinical manifestations and examination. Patient 2: The second patient was a 3-year-old boy and the younger brother of the index patient. He was admitted to our hospital on February 3rd, 2019. The diagnosis of IRD [the onset of clinical manifestations like hearing loss, loss of appetite, slow growth and development, and leukodystrophy was made at 3 years old [3]] was confirmed
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