MILS International
Breaking Diagnostic Barriers with Advanced Metabolic Screening

Advanced metabolic biomarker detection is the next step in improving inborn errors of metabolism (IEM) diagnosis and patient outcomes. Traditional metabolic screening, including urine organic acid analysis and blood acylcarnitine profiling, often fails to reveal the full complexity of IEMs. With over 8,000 known rare diseases, 80 percent of which are hereditary, the need for comprehensive testing has never been more critical.

MILS International, a Japanese government-certified medical testing institution, is redefining metabolic diagnostics with its cutting-edge, untargeted metabolomics platform.

Genetic advancements have led to the identification of more than 1,000 IEMs, revealing the intricate nature of metabolic disorders. Yet clinical testing remains underutilized, limiting the detection of key metabolic abnormalities. MILS bridges this gap with a multifaceted approach that enhances diagnostic capabilities. While urine is the primary testing medium, supplementary blood and cerebrospinal fluid analyses strengthen metabolic marker detection.

"Our IEM metabolomics examination service provides fast, data-driven diagnostics for clinical IEM patients, with continuous advancements to support more clinicians," says Dr. Chunhua Zhang, MD, PhD, and director.

Examining a broader range of metabolic markers enhances disease detection and enables faster, more targeted treatment strategies. A 2023 research report, Comparison of Untargeted Metabolomic Profiling vs. Traditional Metabolic Screening to Identify Inborn Errors of Metabolism by Ning Liu et al., found that untargeted metabolomics achieves a six-fold higher diagnostic yield than conventional screening.

Since 1997, MILS has provided metabolomics testing services to doctors in Southeast Asia and Japan, supporting over 45,000 patients. It has contributed to the confirmed diagnoses of 110 diseases while ensuring industry-leading turnaround times for clinical intervention.

At the helm of MILS' success, Dr. Zhang has been instrumental in advancing its capabilities and solidifying its reputation as a leader in metabolic diagnostics. A globally recognized expert in metabolomics, her work in IEM diagnostics and biomedical mass spectrometry has driven major breakthroughs in rare disease detection. For over two decades, she has led groundbreaking research in high-risk screening and newborn testing using mass spectrometry. As a professor of rare disease medicine at Peking Union Medical College Hospital and a researcher at Kanazawa Medical University, she has contributed significantly to the global understanding of IEM diagnostics. Her contributions to international academic initiatives, including over 130 publications, continue to refine diagnostic methodologies, reinforcing MILS as a trusted partner for clinicians worldwide.

Comprehensive Metabolic Testing for Enhanced Accuracy

MILS expands the diagnostic spectrum with comprehensive biological fluid analyses, enabling a deeper evaluation of metabolic disorders. This includes urine analysis, which is particularly effective in detecting renal tubular and intestinal absorption disorders, conditions where key metabolic markers may be less detectable in blood.

To overcome the limitations of traditional screenings, MILS developed an advanced urine test capable of detecting over 160 IEMs. Backed by more than 20 years of data, this test surpasses conventional urine screenings by offering a broader, more accurate analysis of disorders.

The cerebrospinal fluid analysis further strengthens detection by identifying disease-specific markers that cannot cross the blood-brain barrier. This capability provides critical insights into neurological conditions, allowing for more precise classification of IEMs.

Often missed by traditional testing, critical metabolic disorders, such as aminoaciduria, vitamin and cofactor deficiencies and carbohydrate metabolism disorders, can now be accurately detected. MILS’ metabolomics platform also identifies mitochondrial respiratory chain defects, peroxisomal disorders, nucleic acid metabolism disorders and neurotransmitter abnormalities.

Integrating metabolic signatures with genetic testing, MILS enhances diagnostic accuracy, particularly when dealing with variants of uncertain significance (VUS). The integration provides crucial biochemical evidence to clarify VUS findings, strengthening variant classification. Without metabolic context, determining pathogenicity remains difficult. But combining metabolomic insights with genetic data allows clinicians to translate test results into meaningful clinical insights.

Achieving this level of precision requires cutting-edge analytical techniques. Medical mass spectrometry has become a cornerstone for IEM diagnostics, enabling the study of metabolomics, proteomics and lipidomics to detect diseases. MILS continuously refines its mass spectrometry-based methods, expanding disease detection capabilities through ongoing research and clinical collaboration. The innovative platform is also being explored for applications in early tumor detection, aging prevention and overall health monitoring.

Rapid, Reliable Screening that Saves Lives

MILS delivers robust diagnostic results with unmatched speed, providing reports in 24 to 72 hours and processing urgent cases in as little as three hours. This rapid reporting is particularly beneficial for the swift diagnosis of critically ill patients.

The real-world impact of its speed is demonstrated in several cases.

A one-year-old male from Yokohama, Japan, had been undiagnosed for over a year despite extensive testing, including newborn screenings. The clinical doctor suspected an IEM and contacted MILS for metabolic screening. Within three hours of receiving the urine sample, the technology identified lysinuric protein intolerance (LPI), confirmed by combining the results with blood amino acid analysis and genetic findings. Traditional urine organic acid analysis couldn’t detect LPI due to its metabolic characteristics, including elevated lysine and orotic acid levels, which are not typically identified by standard tests. The ability to assess amino acid levels in urine enabled rapid, accurate diagnosis, providing a clear path for targeted treatment.

Focused initially on pediatric IEM diagnosis, MILS has expanded its metabolomics platform to help detect adult neurological disorders, lipid metabolism issues and cardiovascular diseases. Advanced metabolic profiling has broadened its diagnostic capabilities, with the incorporation of specialized tests that address clinical needs and drive advancements in precision medicine.

A 23-year-old male with spastic paraplegia and severe peripheral neuropathy underwent multiple tests, yet none provided a definitive diagnosis. Metabolic screening at MILS revealed elevated levels of tryptophan and neutral aminoaciduria in his urine, identifying Hartnup disorder, a rare metabolic condition caused by a mutation in the SLC6A19 gene. Doctors initiated proper treatment with this diagnosis, improving the patient's quality of life.

Recognizing the broader applications of metabolic screening, MILS has extended its services to veterinary medicine. Certain genetic conditions in cats and dogs closely resemble those in humans. Through collaboration with veterinary researchers in Japan, Dr. Zhang contributed to advancing the understanding and management of metabolic disorders in animals. Studies on hyperammonemia in cats and dogs have led to exploratory metabolic profiling, uncovering genetic metabolic disorders with direct human parallels.

One notable study, Dihydropyrimidinase Deficiency: The First Feline Case of Dihydropyrimidinuria with Clinical and Molecular Findings, co-published by MILS, has drawn significant attention from the Japanese veterinary community. The research underscores the value of metabolic screening in veterinary care.

Expanding Access to Advanced Metabolic Insights

MILS is advancing global collaboration with the launch of an online data interpretation platform that enables rapid, accurate IEM screening across Asian countries outside Japan.

The platform enables international collaboration among network laboratories, allowing for basic urine sample preparation and GC-MS analysis locally, while complex data is transmitted via the cloud for real-time interpretation by a dedicated team of doctoral-level experts in Japan.

This innovation enhances diagnostic efficiency and technical support for cooperative laboratories, extending access to Japan’s cutting-edge IEM screening services throughout the region.

With over 20 years of international collaboration, it has established strong partnerships with Asia’s two largest IEM laboratories—MILS (Beijing) Medical Laboratory and MILS International India Laboratory, both recognized as leaders in their respective countries. These alliances have helped establish MILS as a trusted authority in IEM diagnostics. The company is further expanding its reach with the development of a new network laboratory in Vietnam, extending high-quality screening services to more countries and patients.

Driving this regional impact is MILS’ ability to seamlessly integrate modern precision medicine with advanced IT infrastructure. A multidisciplinary team of PhD-level detection scientists and data analysts continuously refines analytical techniques and incorporates newly identified biomarkers.

Through rigorous research, clinical collaboration and data validation, the team ensures metabolomics testing remains at the forefront of precision diagnostics, enhancing accuracy and reliability in human and veterinary healthcare.

"We are committed to expanding the frontiers of metabolic disease detection by integrating the latest research, identifying novel biomarkers and continuously evolving our diagnostic capabilities to meet clinical needs," says Dr. Zhang.

Despite its groundbreaking contributions to metabolic disease detection, MILS primarily focused on academic research rather than commercial outreach. Clinician awareness was limited, with many continuing to rely on traditional screening methods due to familiarity and cost considerations, even as diagnostic technology advanced.

To promote the adoption of metabolomics-based diagnostics, MILS actively participates in international quality assessments. Organizations like the College of American Pathologists (CAP) and the European Research Network for evaluation and improvement of screening, Diagnosis and treatment of Inherited disorders of Metabolism (ERNDIM) conduct external quality assessments to ascertain the accuracy of IEM testing labs. MILS has participated in ERNDIM since 2006 and CAP since 2019, consistently earning top-tier certifications. The company has also gained accreditation from the Japanese Society of Congenital Metabolic Diseases and is designated as a special examination institution in Japan.

Rare diseases are no longer mysteries. MILS International is accelerating the path to precise diagnoses, empowering clinicians with advanced insights to deliver timely, targeted treatments.