Table 2.

Monogenic Kidney Diseases in the Differential Diagnosis of ADTKD-MUC1

Gene(s)DisorderMOIRenal PhenotypeDistinguishing Features of this Disorder vs ADTKD-MUC1
Most likely disorders to consider
UMOD ADTKD-UMOD ADProteinuria is rare; slowly progressive CKDGout often occurs during adolescence in ADTK-UMOD. Otherwise, it presents very much like ADTKD-MUC1.
REN ADTKD-REN ADSlowly progressive CKD w/anemia, metabolic acidosis, hyperkalemia, & mild hypotension, often presenting in childhood. Gout may occur in late teens & adolescence.ADTKD-REN presents more often in childhood than ADTKD-MUC1 & is assoc w/hyperkalemia, metabolic acidosis, & anemia.
Other disorders to consider
CEP290
INVS
IQCB1
NPHP1
NPHP3
NPHP4
TMEM67
(19 genes 1)		Isolated nephronophthisis (NPH)ARTubulointerstitial kidney disease; often seen in childhood & can be assoc w/anemia & mild hypotension
  • Absence of affected family members in multiple generations
  • ESRD usually occurs earlier (affected persons usually require dialysis in teens & early 20s).
COL4A3
COL4A4
COL4A5 		Alport syndrome (& other types of hereditary glomerulonephritis)XL
AR
AD		Microscopic hematuria (microhematuria); proteinuria; progression to ESRDFrequent cochlear & ocular manifestations; hematuria; males affected much more severely than females
DNAJB11
GANAB
PKD1
PKD2 		Autosomal dominant polycystic kidney disease (ADPKD)ADBland urinary sediment 2; large # of cysts in persons age >25 yrsNumerous cysts seen on kidney ultrasound
GLA Fabry disease, classic formXLProteinuria (usually > than in ADTKD-UMOD); gradual deterioration of renal function to ESRD occurs in ~3rd-5th decade 3Classic form (males w/<1% α-Gal A activity) usually has onset in childhood or adolescence w/periodic crises of severe pain in extremities (acroparesthesias), appearance of vascular cutaneous lesions (angiokeratomas), hypohidrosis, & characteristic corneal & lenticular opacities.
DNAJB11 4Atypical ADPKD-ADTKDADSlowly progressive chronic kidney disease, multiple renal cysts.Numerous kidney cysts are common.
HNF1B ADTKD-HNF1BADVariable presence of other manifestations accompany renal disease, incl MODY, hyperuricemia, hypomagnesemia & gout, CKD, CAKUT, & unexplained liver function test abnormalities.
mtDNAm.547A>T 5MatChronic tubulointerstitial kidney disease
PAX2 PAX2-related disorder ADGlomerular proteinuria & hematuriaGlomerular renal disease w/hematuria, proteinuria, & ocular coloboma
SEC61A1 ADTKD-SEC61A1ADSlowly progressive CKD
  • Leukopenia (w/abscess formation), intrauterine & postnatal growth restriction
  • Renal disease often presents in childhood.

AD = autosomal dominant; AR = autosomal recessive; CAKUT = congenital anomalies of the kidneys and urinary tract; CKD = chronic kidney disease; ESRD = end-stage renal disease; Mat = maternal; MODY = maturity-onset diabetes of the young; MOI = mode of inheritance; mt(DNA) = mitochondrial; XL = X-linked

1.

Listed genes represent the most common genetic causes of isolated nephronophthisis (NPH). Other genes known to be associated with nephronophthisis are ANKS6, CEP164, CEP83, DCDC2, GLIS2, IFT172, NEK8, RPGRIP1L, SDCCAG8, TTC21B, WDR19, and ZNF423.

2.

Bland refers to urinary sediment with little blood or protein.

3.

Males with >1% α-Gal A activity have a cardiac or renal variant phenotype. Rarely, heterozygous (carrier) females may have symptoms as severe as those observed in males with the classic phenotype.

4.
5.

From: Autosomal Dominant Tubulointerstitial Kidney Disease – MUC1

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