Condition: morbidity, mortality, natural history, epidemiology. Test: reliability, precision, clinical validity, confirmatory testing. Treatment: Availability, effectiveness, medical expertise. Screening program: effectiveness, benefits, cost, quality assurance, fu, outcome monitoring. Defect of urinary dibasic amino acid transport. Elevated urinary excretion of cystine, lysine, arginine, ornithine. Present: kidney stones, urinary tract infection, pain, hematuria, normal mentality. Genes: SLC3A1, SLC7A9.
Type 1: fully recessive. Heterozygotes have normal excretion of cystine and dibasic aa. Mutations to rBAT (SLC3A1).
Types 2 and 3: incomplete recessive form. Heterozygotes excrete cystine and dibasic aa at levels greater than normal. Mutations in b0+AT (SLC7A9)
Dx: plasma and urine aa (High cystine, arginine, lysine, ornithine, glycine), with decreased reabsorption of cystine. Quant reabsorption studies sometimes needed.
Tx: Stones prevented by dilution in larger urine volumes.
High urine aa: alanine, serine, threonine, valine, leucine, isoleucine, phenylalanine, tyrosine, tryptophan, glutamine, aspargine, histidine. Defective intestinal transport of these aa. Cause: Defective neutral aa transporter SLC6A19 gene.
Presentation: attacks of cerebellar ataxia, mild emotional lability, frank delirium. Also exacerbations of erythematous, eczemoatoid skin rash. Fever, sunlight, stress and sulfonamide therapy provoke relapses. Only a small fraction develop pellagra-like syndrome.
Tx: niacin repletion w/ high-protein diet and daily nicotinamide supplementation
Growth restriction, senile appearance, premature and dysplastic dentition, pineal hyperplasia, lack of subcutaneous fat, acanthosis nigricans, enlargement of genitalia, hirsutism, abnormal glucose homeostasis, hyperinsulinemia, prolonged survival (5-15yrs). Fasting hypoglycemia early in life followed by hyperglycemia, but no ketosis and finally by severe ketoacidosis. Progressive decline in insulin levels with age. Progressive dependence of insulin levels on glucose concentration. Drugs such as barbiturates, tranquilizers, birth control pills, sedatives. Chemicals, fasting, smoking, alcohol (esp heavy), infections, excess iron, emotional/physical stress, mentrual hormones, exposure to sun. Most frequent type of porphyria. Decreased uroporhyringogen decarboxylase (URO-D) activity. Inherited AD. Tx: phlebotomy, low-dose chloroquine.
F-PCT: familial (hereditary) variant. 50% normal enzyme activity and other factors are needed for symptoms. 25% of all cases of PCT
S-PCT: sporadic variant, approx 70% of PCT. Enzymatic def is only in liver, no mutations in URO-D gene. Assoc w/ 1+ risk factors including (homozygosity of C282Y mutation HFE, hepatitis C, alcohol abuse, use of medical estrogens).
Present: skin fragility on dorsal side of hands, blistering on all sun-exposed areas. Blisters rupture, heal slowly, then form thick eschars, then hyperpigmented patches. Facial hypertrichosis is common esp in children and women. Scleroderma-like skin changes develop in light exposed areas in some pt.
Dx: Total porphyrin content in plasma is elevated. If plasma porphyrins are elevated, the urinary porphyrin profile can provide the dx. Measure URO-D activity in red blood cells or DNA testing confirmes F-PCT.