Advanced Diagnostic System and Introduction of Newborn Screening of Adrenoleukodystrophy and Peroxisomal Disorders in Japan.

Nobuyuki Shimozawa,Kenji Orii,Megumi Ogawa,Shigeo Takashima,Hiroki Kawai,Hideo Sasai,Hidenori Ohnishi,Kazuo Kubota

doi:10.3390/ijns7030058

Nobuyuki Shimozawa, Kenji Orii + Show 6 more

Open Access

https://doi.org/10.3390/ijns7030058

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Abstract

We established a diagnostic system for adrenoleukodystrophy (ALD) and peroxisomal disorders (PD) over 35 years ago in Japan, and have diagnosed 237 families with ALD and more than 100 cases of PD other than ALD using biochemical and molecular analyses. In particular, since the only treatment for the cerebral form of ALD is hematopoietic stem cell transplantation at an early stage of onset, we have developed a protocol for the rapid diagnosis of ALD that can provide the measurements of the levels of very-long-chain fatty acids in the serum and genetic analysis within a few days. In addition, to improve the prognosis of patients with ALD, we are working on the detection of pre-symptomatic patients by familial analysis from the proband, and the introduction of newborn screening. In this review, we introduce the diagnostic and newborn screening approaches for ALD and PD in Japan.

Highlights

Peroxisomal disorders (PD) are inborn errors of metabolism that affect the metabolic function of peroxisomes, and can be divided into two groups: peroxisome biogenesis disorder (PBD) and single enzyme deficiency (SED) [1]
SED is caused by genetic abnormalities in proteins localized in the peroxisomes, and PBD is caused by genetic abnormalities in proteins involved in the transport of these proteins to the peroxisomes and in the biosynthesis of peroxisomal membranes
Adrenoleukodystrophy (ALD), the most common PD, is an X-linked inherited disease caused by a pathogenic mutation in the ABCD1 gene and a dysfunction of its product, ABCD1, a peroxisomal membrane protein involved in the import of saturated very-longchain fatty acids (VLCFA) into the peroxisomes, leading to impaired β-oxidation of saturated VLCFA

Summary

Introduction

Peroxisomal disorders (PD) are inborn errors of metabolism that affect the metabolic function of peroxisomes (intracellular organelles), and can be divided into two groups: peroxisome biogenesis disorder (PBD) and single enzyme deficiency (SED) [1]. Adrenoleukodystrophy (ALD), the most common PD, is an X-linked inherited disease caused by a pathogenic mutation in the ABCD1 gene and a dysfunction of its product, ABCD1, a peroxisomal membrane protein involved in the import of saturated very-longchain fatty acids (VLCFA) into the peroxisomes, leading to impaired β-oxidation of saturated VLCFA. This results in the accumulation of saturated VLCFA in the tissues and plasma. As the only center for the diagnosis of PD in Japan, we have diagnosed many patients with PD through the diagnostic screening of peroxisomal metabolites and with biochemical and genetic analyses for 35 years. We present our efforts to diagnose ALD and PD and introduce newborn screening in Japan

Diagnostic System for ALD and PD in Japan

Efforts to Diagnose ALD before the Onset of Cerebral Type at Gifu University

Introduction of the ALD Newborn System in the Gifu Prefecture

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Discussion

Conclusions