Note: Intro -- Contents -- Part I Reports on Alkaptonuria -- Analysis of HGD Gene Mutations in Patients with Alkaptonuria from the United Kingdom: Identification of Novel Mutations -- Abstract -- Introduction -- Material and Methods -- Subjects -- Mutation Analysis of the HGD Gene -- Results and Discussion -- Conclusion -- Compliance with Ethics Guidelines -- Informed Consent -- Details of the Contributions of Individual Authors -- References -- Metabolic Effects of Increasing Doses of Nitisinone in the Treatment of Alkaptonuria -- Abstract -- Introduction -- Methods -- Patient Enrollment -- Sample Storage -- Sample Preparation -- Sample Acquisition Methods -- Statistical Analysis -- Results -- HGA in Urine -- Tyrosine and NTBC in Plasma -- Untargeted Metabolomics Analysis -- Patient Symptoms -- Discussion -- Synopsis -- Compliance with Ethics Guidelines -- Conflicts of Interest -- Informed Consent -- Author Contributions -- References -- Relationship Between Serum Concentrations of Nitisinone and Its Effect on Homogentisic Acid and Tyrosine in Patients with Alka... -- Abstract -- Introduction -- Materials and Methods -- Patients -- Study Design and Treatments -- Measurements -- Calculations and Statistics -- Results -- Demographics -- Nitisinone Pharmacokinetics -- Relationship Between Nitisinone Exposure and the Effect on HGA and Tyrosine -- Discussion -- Synopsis (Take-Home Message) -- Compliance with Ethics Guidelines -- Conflict of Interest -- Contributors -- References -- Investigating the Robustness and Diagnostic Potential of Extracellular Matrix Remodelling Biomarkers in Alkaptonuria -- Abstract -- Introduction -- Methods -- Clinical Cohort -- Measurements -- Robustness Analysis -- Creatinine Assessment -- Assessment of HGA Interference with Hydroxyperoxidase-Based ELISAs -- Results -- Robustness Analysis of the Biomarkers. , Interference of HGA with Enzyme-Based Assays -- Diagnostic Markers of ECM Remodelling in AKU -- Discussion -- Conclusions -- Synopsis -- Compliance with Ethics Guidelines -- Conflict of Interests -- Informed Consent -- Details of the Contributions of Individual Authors -- References -- Age-Related Deviation of Gait from Normality in Alkaptonuria -- Abstract -- Introduction -- Participants and Methods -- Results -- Discussion -- Conclusions -- Take-Home Message -- Compliance with Ethics Guidelines -- Conflict of interests -- Informed Consent -- Contributions of Individual Authors -- References -- Nitisinone Arrests but Does Not Reverse Ochronosis in Alkaptonuric Mice -- Abstract -- Introduction -- Materials and Methods -- Mice -- Sample Preparation -- Chromatographic Conditions -- Midlife Nitisinone Treatment -- Nitisinone Dose-Response -- Histological Analysis -- Quantification of Pigmented Chondrons -- Statistical Analyses -- Results -- Discussion -- Synopsis -- Compliance with Ethics Guidelines -- Conflicts of Interest -- Animal Rights -- Author Contributions -- References -- The Pigment in Alkaptonuria Relationship to Melanin and Other Coloured Substances: A Review of Metabolism, Composition and Che... -- Abstract -- Introduction -- Background -- Melanins -- Melanin Types -- Biosynthetic Pathways of Eumelanin and Pheomelanin -- Pigmentation in AKU: The Nature of the Pigment -- Analysis/Detection of the Melanin Types -- Analysis of Pigment Derived from HGA -- Compliance with Ethics Guidelines -- Conflict of Interest -- References -- Part II Case and Research Reports -- Serum GDF15 Levels Correlate to Mitochondrial Disease Severity and Myocardial Strain, but Not to Disease Progression in Adult ... -- Abstract -- Introduction -- Methods -- Patients -- GDF15 -- Medical Ethical Approval -- Myocardial Strain Measurement -- Statistics -- Results. , Patient Characteristics -- The Value of GDF15 as an Indicator of Clinical Disease Severity -- Covariates for the Concentration of GDF15 -- The Value of GDF15 in Predicting Clinical Disease Progression -- Myocardial Strain -- Family-Matched Controls -- Discussion -- Take-Home Message -- Conflict of Interest -- Informed Consent -- Details of the Contributions of Authors -- References -- Novel Genetic Mutations in the First Swedish Patient with Purine Nucleoside Phosphorylase Deficiency and Clinical Outcome Afte... -- Abstract -- Introduction -- Patient -- Investigations -- Genetic and Enzymatic Analysis -- Transplantation -- Engraftment and Immunological Reconstitution -- Posttransplant Morbidity -- Neurological Development -- Literature Review -- Discussion -- Conclusion -- Synopsis -- Compliance with Ethics Guidelines -- Informed Consent -- Author Contributions -- Conflict of Interest -- References -- CSF 5-Methyltetrahydrofolate Serial Monitoring to Guide Treatment of Congenital Folate Malabsorption Due to Proton-Coupled Fol... -- Abstract -- Introduction -- Case Report -- Results -- Discussion -- Conclusion -- Compliance with Ethics Guidelines -- Conflict of Interest: -- Informed Consent -- References -- A Novel Catastrophic Presentation of X-Linked Adrenoleukodystrophy -- Abstract -- Introduction -- Case Presentation -- Discussion -- Conclusion -- Synopsis -- Compliance with Ethics Guidelines -- Conflict of Interest -- Informed Consent -- Author Contributorship Statement -- References -- High Incidence of Biotinidase Deficiency from a Pilot Newborn Screening Study in Minas Gerais, Brazil -- Abstract -- Introduction -- Methods -- DNA Sequencing -- Results -- Discussion -- Synopsis -- Compliance with Ethics Guidelines -- Conflict of Interest -- Informed Consent -- Details of the Contributions of Individual Authors -- References. , Dopamine-Responsive Growth-Hormone Deficiency and Central Hypothyroidism in Sepiapterin Reductase Deficiency -- Abstract -- Introduction -- Case Summary -- History and Examination -- Treatment and Follow-Up -- Discussion -- Conclusion -- Synopsis -- References to Electronic Databases -- Competing Interest Statement -- Details of Contributions of Individual Authors -- Name of One Author Who Serves as Guarantor -- Ethical Approval -- References -- Clinical Findings and Natural History in Ten Unrelated Families with Juvenile and Adult GM1 Gangliosidosis -- Abstract -- Introduction -- Patients and Methods -- Results -- Discussion -- Conclusions -- Synopsis -- Compliance with Ethics Guidelines -- Conflict of Interest Statement -- Informed Consent -- Animal Rights -- Details of Author Contributions -- References -- High Incidence of Serologic Markers of Inflammatory Bowel Disease in Asymptomatic Patients with Glycogen Storage Disease Type ... -- Abstract -- Background -- Methods -- Results -- Discussion -- Conclusions -- Synopsis -- Compliance with Ethics Guidelines -- Conflict of Interest -- Informed Consent -- Details of the Contributions of Individual Authors -- References.