Metabolic - Diseases Flashcards
Rickets / Osteomalacia
Results from Vitamin D deficiency in children / adults, respsectively; presents as bony deformity and bone pain (Rickets) with progressive softening of bones (osteomalacia)
Labs: Hypocalcemia, hypophosphatemia, elevated ALP, elevated PTH
Findings: Chvostek’s sign, Trousseau sign
Treatment: Vitamin D supplementation
Maple Syrup Urine Disease
Autosomal recessive defect in alpha-ketodehydrogenase, responsible for the metabolism of branched amino acids (Leucine, Isoleucine, Valine)
Results in increased alpha-ketoacids in the blood
Presents with sweet-smelling urine, severe CNS abnormalities/intellectual disability, and death in infancy
Treatment: Dietary restriction of branched AAs; thiamine supplementation
Tay Sach’s Disease
Autosomal recessive deficiency of Hexosaminidase A responsible for conversion of GM2 ganglioside to GM3 ganglioside
Presents with progressive neurodegeneration, intellectual disability, “cherry red spot” on the macula
NO hepatosplenomegaly
Niemann-Pick Disease
Autosomal recessive deficiency of sphingomyelinase, with accumulation of sphingomyelin
Presents with progressive neurodegeneration, intellectual disability, “cherry red spot” on the macula PLUS hepatosplenomegaly
Scurvy
Vitamin C deficiency, necessary for hydroxylation of proline and lysine in collagen synthesis
Presents with bleeding, petechiae, swollen gums, hemarthroses, and “corkscrew hair”
Hunter Syndrome
X-linked recessive deficiency of iduronate sulfatase
Affected males present with mild intellectual disability, hearing loss, coarse facies, hepatosplenomegaly
NO corneal clouding (vs. Hurler syndrome)
Hurler Syndrome
Autosomal recessive defect of alpha iduronidase; boys and girls affected equally
Presents with developmental delay, airway obstruction, hepatosplenomegaly + corneal clouding
Essential fructosuria
Autosomal recessive defect in fructokinase causing benign, asymptomatic presence of fructose in the blood and urine
Fructose intolerance
Autosomal recessive Aldolase B deficiency; causes accumulation of Fructose-1-Phosphate, which diminishes stores of available phosphate; decreased phosphate inhibits glycogenolysis and gluconeogenesis
Presents with hypoglycemia, jaundice, and vomiting following ingestion of fruit, juice, and honey
Dx: Reducing sugars in urine (non-specific)
Treatment: Reduced dietary intake of fructose and sucrose
Galactokinase Deficiency
Autosomal recessive; leads to accumulation of Galactitol via shunting down an alternative metabolic pathway
Relatively mild; presents with infantile cataracts + galactose in blood and urine
Galactosemia
Autosomal recessive defect in Galactose-1-Phosphate Uridyltransferase leads to depletion of phosphate stores and accumulation of toxic metabolites including Galactitol
Presents with failure to thrive, jaundice, hepatomegaly, infantile cataracts, and intellectual disability
Treatment - elimination of dietary galactose and lactose (including breast milk and lactose-containing formulas)
Porphyria Cutanea Tarda
Most common porphyria
Due to defect of uroporphyrinogen decarboxylase enzyme of heme biosynthetic pathway, resulting in accumulation of uroporphyrin
Presents with blistering cutaneous photosensitivity and tea-colored urine
Acute Intermittent Porphyria
Second most common porphyria; due to deficiency of enzye porphobilinogen deaminase with accumulation of porphobilinogen
Presentation - 5Ps: Painful abdomen, port wine-colored urine, polyneuropathy, psych disturbances, precipitated by alcohol, drugs, or starvation
Treated with glucose and heme
Alktaptonuria
Autosomal recessive deficiency of homogentisic oxidase, an enzyme in the tyrosine degradation pathway
Accumulation of homogentisic acid leads to dark pigmentation of connective tissue (sclerae, pinnae); usually benign but sometimes associated with arthralgias
Findings: Urine turns black upon standing
Milk Alkali Syndrome
Hypercalcemia + Metabolic alkalosis + Renal insufficiency
Presents with fatigue, depressed mood, muscle weakness, constipation/abdominal pain; commonly occurs secondary to OTC Ca-containing antacid use
Findings: High calcium, low phosphate, low potassium, high bicarbonate, high BUN, high CrCl
