Diagnosis of an intermediate case of maple syrup urine disease:A case report

BACKGROUND Maple syrup urine disease(MSUD)is an autosomal recessive genetic disorder caused by defects in the catabolism of the branched-chain amino acids(BCAAs).However,the clinical and metabolic screening is limited in identifying all MSUD patients,especially those patients with mild phenotypes or are asymptomatic.This study aims to share the diagnostic experience of an intermediate MSUD case who was missed by metabolic profiling but identified by genetic analysis.CASE SUMMARY This study reports the diagnostic process of a boy with intermediate MSUD.The proband presented with psychomotor retardation and cerebral lesions on magnetic resonance imaging scans at 8 mo of age.Preliminary clinical and metabolic profiling did not support a specific disease.However,whole exome sequencing and subsequent Sanger sequencing at 1 year and 7 mo of age identified bi-allelic pathogenic variants of the BCKDHB gene,confirming the proband as having MSUD with non-classic mild phenotypes.His clinical and laboratory data were retrospectively analyzed.According to his disease course,he was classified into an intermediate form of MSUD.His management was then changed to BCAAs restriction and metabolic monitoring conforming to MSUD.In addition,genetic counseling and prenatal diagnosis were provided to his parents.CONCLUSION Our work provides diagnostic experience of an intermediate MSUD case,suggesting that a genetic analysis is important for ambiguous cases,and alerts clinicians to avoid missing patients with non-classic mild phenotypes of MSUD.

Actively separated microneedle patch for sustained-release of growth hormone to treat growth hormone deficiency

Growth hormone deficiency(GHD)has become a serious healthcare burden,and presents a huge impact on the physical and mental health of patients.Here,we developed an actively separated microneedle patch(PAA/NaHCO_(3)^(-)Silk MN)based on silk protein for sustained release of recombinant human growth hormone(rhGH).Silk protein,as a friendly carrier material for proteins,could be constructed in mild full-water conditions and ensure the activity of rhGH.After manually pressing PAA/NaHCO_(3)^(-)Silk MN patch to skin for 1 min,active separation is achieved by absorbing the interstitial fluid(ISF)to trigger HCO_(3)^(-)in the active backing layer to produce carbon dioxide gas(CO_(2)).In rats,the MN patch could maintain the sustained release of rhGH for more than 7 days,and produce similar effects as daily subcutaneous(S.C.)injections of rhGH in promoting height and weight with well tolerated.Moreover,the PAA/NaHCO_(3)^(-)Silk MN patch with the potential of painless self-administration,does not require cold chain transportation and storage possess great economic benefits.Overall,the PAA/NaHCO_(3)^(-)Silk MN patch can significantly improve patient compliance and increase the availability of drugs,meet current unmet clinical needs,improve clinical treatment effects of GHD patients.