A child with a history of coarse facial features, joint stiffness, and a cardiac murmur is found to have valvular thickening. In mucopolysaccharidoses, substrate accumulation within the extracellular matrix most directly leads to progressive thickening and dysfunction of which of the following specific structures?
A toddler has severe abdominal pain, vomiting, and muscle weakness after fasting overnight. Physical exam reveals hepatomegaly, and labs show ketotic hypoglycemia with elevated creatine kinase and mildly elevated uric acid, but normal lactate. What condition is most likely?
A child presents with lethargy, poor feeding, vomiting, and hypotonia in the neonatal period, with metabolic acidosis, ketosis, hyperammonemia, and secondarily elevated plasma and urinary glycine. Which mutation is most probably found?
An 8-year-old child presents with growth failure, alopecia, joint contractures, generalized lipodystrophy, and a high-pitched voice. Physical exam reveals prominent scalp veins, a small face relative to head size, and skin changes resembling scleroderma. Cardiovascular evaluation reveals increased carotid artery pulse wave velocity, consistent with early atherosclerosis. Genetic testing confirms a de novo LMNA mutation. Which medication is FDA-approved to reduce the risk of mortality in this condition?
A neonate with feeding difficulty and hypotonia is found to have high plasma leucine, isoleucine, valine, and alloisoleucine. What is the primary treatment?
A 7-year-old with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency is treated during episodes of muscle pain and hypoglycemia. Which secondary laboratory abnormality may be seen?
A 7-year-old child with severe dystonia and diurnal variation of symptoms has low CSF homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) with normal blood phenylalanine. Upon phenylalanine loading, plasma phenylalanine/tyrosine remains elevated. Which gene is most likely affected?
A 5-year-old has intellectual disability, fair complexion, eczema, and a musty body odor. Which of the following is likely reduced in the brain?
A 5-month-old presents with failure to thrive, progressive hepatosplenomegaly, and signs of evolving liver cirrhosis with ascites. Liver biopsy reveals abnormal glycogen with markedly fewer branch points and long outer chains. Which enzyme is most likely deficient?
A preschooler develops vomiting, hypotonia, severe acidosis, and ketoacidosis during fasting. Urine organic acids reveal massive 2-methylacetoacetate, mild hyperglycinemia, and C5:1 and C5-OH carnitine elevations during crises but normal in between. What is likely to reveal the diagnosis between episodes?
