Cause:Genetic, autosomal recessive on chromosome 17
Pathophys:
Fanconi’s syndrome (see Fanconi's Syndrome) due to damage to proximal renal tubules
Ocular (adult-onset) variant pts have partial gene preservation and have only eye findings, no renal involvement
Sx:Onset as early as 4-6 mo in childhood type, or in adulthood
Si:Rickets, hepatosplenomegaly, corneal opacities (cystine deposition), peripheral retinal patchy depigmentation in children only
Increased mental retardation (Nejm 1970;283:783); myopathy (Nejm 1988;319:1461) including swallowing dysfunction (Nejm 1990;323:565); Fanconi’s syndrome; renal tubular acidosis
Rx:
Prevent by detection of carriers (Nejm 1982;306:1468)
Cysteamine (Cystagon) (Med Let 1994;36:116) or phosphocysteamine rx started before age 2 yr for 7+ yr prevents renal disease, then pt has a good renal prognosis (Nejm 1993;328:1157)
Renal transplant
Table 17.5 Other Renal Tubular Defects
| Disease | Amino acid/sugar | Presenting Sx |
|---|---|---|
| Homocystinuria | Homocystine | (Homocystinuria (Homocyst(e)inemia)) |
| Cystinosis (Ann IM 1988;109:557) | Cystine | Rickets, hepatosplenomegaly, corneal opacities, retinopathy, uremia, mental retardation, myopathy including swallowing dysfunction (New Eng J Med 1990;323:565), Fanconi syndrome, RTA; rectal bx diagnostic; rx by detecting carriers and treating pts w cystamine |
| Cystinuria (New Eng J Med 1992;327:1141) | Cystine (the sulfide, of cysteine), arginine, ornithine | Calcified hexagonal renal stones and renal calcinosis; false pos urine acetone tests; rx with alkalinization of the urine, and decreasing dietary methionine; salt restrict (Nejm 1986;315:1120); then D-penicillamine or tiopronin (Med Let 1989;31:7) |
| Hartnup's | Val, Leu, Tryp, Tyr, Ala, Ser, isoL, Glut, His, Threon, Asp | Diarrhea, dementia, dermatitis. Pellagra disease and neurologic ataxia in attacks which are improved by nicotinamide po |
| Iminoglycinuria | Gly, Pro, Hpro | Deafness (New Eng J Med 1968;278:1407) |
| Methionine | Met | Mental retardation, white hair, foul stools (malabsorption); rx w low met diet |
| Joseph's syndrome | Pro, Hpro, Glyc | Convulsive infant, die young |
| Histadinemia | Hist | Benign (New Eng J Med 1974;291:1214) |
| Pentosuria | Pentoses | Not a renal defect; systemic defect in pentose-phosphate shunt. 1/50 000 Jews (New Eng J Med 1970;282:892) |
| Maple syrup urine disease | Branched chain amino acid metabolism defect | Growth failure and psychomotor retardation; rx with dialysis and branched chain amino acid-free diet (New Eng J Med 1991;324:175) |