Renal Flashcards
Anion gap calculation
Normal anion gap = 8-16 (Na + K ) - (Cl + HCO3)
Absorption in the proximal tubule
- Active Na reabsorption (60%) - Bicarb reabsorption (85-90%) - Secondary reabsorption of; Glucose Phosphate Amino acids LMW proteins Chloride
What is TYPE II renal tubular acidosis?
Proximal tubular acidosis Primary defect = impairment of HCO3- reabsorption in the proximal tubule
What is Fanconi’s syndrome?
Global proximal tubular dysfunction
Key features of Renal Fanconi syndrome
- LMW proteinuria - Glycosuria - Hypophosphataemia - Aminoaciduria - Hypouricaemia - Bicarb loss
Aetiology of Fanconi syndrome
Inherited - AR (mutation in gene encoding Na/HCO3 co transporter); short stature, blindness, enamel defects of teeth, ID - Cystinosis (AR mutation in CTNS gene) - Dent disease (X-linked recessive) OCRL 1 defect of CLC5 defect - Lowe syndrome (X-linked recessive), OCRL1 gene defect; congenital cataracts, mental retardation, Fanconi - Mitochondrial myopathies Metabolic disorders - Tyrosinemia type 1 - Galactosemia - Wilson’s disease - Hereditary fructose intolerance Heavy metal toxicity Drugs - Gentamicin - Cisplatin - Sodium valproate - Ifosfamide
LOWE syndrome triad
Congenital cataracts Mental retardation Fanconi syndrome
Distinguishing features between Dent disease + Lowe syndrome
Dent disease is distinguished clinically from the Lowe (oculocerebrorenal) syndrome by the absence of cataracts, mental developmental delay, and renal tubular acidosis.
Dent disease clinical features
LMW proteinuria Hypercalciuria (due to increased GIT Ca absorption) Nephrocalcinosis Kidney stones Kidney failure Rickets Polyuria Microscopic haematuria
Treatment of RTA type II
Sodium bicarbonate Potassium citrate (citrate also increases HCO3 levels) Oral phosphate Vitamin D
RTA type 1
Distal tubular dysfunction Impaired secretion of H+ in distal nephron Inability to excrete daily acid load - Progressive loss of buffer - Serum HCO3- <10 - Urine pH > 5.5 - Hypokalaemia with Na wasting - Hypercalciuria with risk of stones + nephrocalcinosis POSITIVE urine anion gap (Na + K) - (Cl)
Urine pH + RTA type 1
IF you have high levels of SERUM bicarb (e.g. on replacement) then the urine pH will HIGH IF you have LOW levels of SERUM bicarb the urine pH will be LOW as you will be in a metabolic acidosis and the distal tubules still work so will be actively pumping out H+ ions to try and improve the metabolic acidosis
RTA type I and II can cause a _____ anion gap metabolic ______
RTA type I and II can cause a NORMAL anion gap metabolic ACIDOSIS
RTA type I causes
PRIMARY - AD + AR mutations - Defects in Cl/HCO3 exchanged, carbonic anhydrase or H+ATPase - AR associated with SNHL SECONDARY - Autoimmune disorders - Nephrocalcinosis - Drugs: ifosfamide, amphotericin, lithium, ibuoprofen - Hypercalciuric conditions (hyperPTH, vit D intoxication) - EDS, Wilson, Marfan’s
What is cystinosis?
Systemic disease caused by a defect in the metabolism of cysteine that results in accumulation of cysteine crystals in the major organs of the body
Genetics of cystinosis
AR mutation in CTN5 gene
Clinical manifestations of cystinosis
i. Polyuria and polydipsia ii. Growth failure iii. Rickets iv. Fever – caused by dehydration or diminished sweat production v. Patients typically fair skinned and blond due to diminished pigmentation vi. Ocular presentations – photophobia, retinopathy, impaired visual acuity vii. Other – hypothyroidism, hepatosplenomegaly, delayed sexual maturation viii. With progressive tubulointerstitial fibrosis → renal fibrosis
Diagnosis of cystinosis
- Cystine crystals in the cornea
- White cell cysteine:
- Leukocyte cysteine content = elevated; confirms diagnosis
Treatment of cystinosis
i. Aimed at correcting metabolic abnormalities associated with Faconi syndrome or chronic renal failure ii. Cysteamine – which binds to cystine and converts it to cysteine 1. Oral = facilitates lysosomal transport and decreases tissue cysteine 2. Eye drops = oral cysteamine does not achieve adequate levels in ocular tissue 3. Early initiation of the drug can prevent or delay deterioration in renal function iii. GH – patients with growth failure that does not improve with cysteamine may benefit from GH iv. Kidney transplant – option for patients in renal failure v. BMTx
Investigation results (blood + urine) in RTA type I
Blood i. Non-anion gap (hyperchloraemic) metabolic acidosis ii. Hypokalaemia (due to hyperaldosteronism iii. Hyperammonaemia Urine i. Alkaline urine (pH >5.5) ii. HIGH urinary calcium iii. LOW urinary citrate a. Alkaline urine = due to impaired hydrogen ion excretion, urine pH cannot be reduced to <5.5, despite the presence of severe metabolic acidosis b. Hyperchloraemia = loss of sodium bicarbonate distally, owing to lac of H+ to bind to in the tubular lumen, results in increased chloride absorption and hyperchloraemia c. Hypokalaemia = inability to secrete H+ is compensated by increased K+ secretion distally, leading to hypokalaemia d. Hypercalciuria = usually present and can lead to nephrocalcinosis or nephrolithiasis e. Hypocitraturia = chronic metabolic acidosis impaired urinary citrate excretion; further increases the risk of calcium deposition in the tubules
RTA type I vs. type 2
Urine pH is < 5.5 (able to resorb HCO3 distally + excrete H+ distally) in proximal (type 2) Bicarb is higher in proximal type 2 Hypokalemia occurs in both – improves with therapy in distal, worsens in proximal Nephrocalcinosis a feature of distal RTA (type 1) Fanconi syndrome is a feature of proximal RTA (type 2) POSITIVE urine anion gap in type 1 Rickets more common in type 2
RTA type IV definition + causes
Decreased production or response to aldosterone in the collecting duct PRIMARY - Hypoaldosteronism - Addison’s - CAH - Pseudohypoaldosteronism SECONDARY - Obstructive uropathy - Pyelonephritis - Interstitial nephritis - Diabetes - Sickle cell nephropathy - ACEI, spironolactone, amiloride
Aldosterone - Secreted by - Acts on - Actions
Secreted by zona glomerulosa cells of the adrenal cortex Acts via mineralocorticoid receptor Acts on the principal cells of the cortical collecting tubule Increases reabsorption of Na - Increases no. ENAC channels luminal side - Increases Na/K/ATPase pump on basolateral side Increases excretion K+ - Reabsorption of NA from lumen creates luminal negativity which drive K+/ H+ secretion Increases excretion of H+
Features of Bartter’s Syndrome
**Biochemical features resemble those seen with chronic loop diuretic use** Hypokalaemia Hypochloraemia Metabolic alkalosis Normotensive hyperreninaemia Increased urinary excretion K Cl Na Ca Hypercalciuria
Clinical features of Bartter’s
Onset in first 2 yrs of life Often polyhydramnios + preterm labour if severe ‘antenatal’ variant Polyuria, polydipsia Vomiting Constipation Salt craving Dehydration FTT Fatigue / weakness / cramps Developmental delay Nephrocalcinosis
Bartter’s Syndrome pathophysiology
Defective reabsorption of NaCl in TAL LOH Distal tubular sodium sites overwhelmed = polyuria (resembles nephrogenic DI BUT urine osmolality often >100mosmol/L + responds to DDAVP) Polyuria + low serum Na = RAAS - Hypertrophy of JGA - Hyperaldosteronism = Na uptake + K excretion + H+ secretion distally - Exacerbates hypokalaemia + alkalosis Hypokalaemia stimulates PG = further NaCl wasting Unable to generate a POSITIVE potential in the tubular lumen due to reduced Na reabsorption = reduced Ca reabsorption
Bartter’s Syndrome genetics
Autosomal recessive Type I: NKCC2 transporter defect, antenatal Type II: ROMK transporter defect, antenatal Type III: ClC-KB transporter defect (no nephrocalcinosis), classic Type IV: Barttin defect, antenatal (deafness)
Treatment of Bartter’s Syndrome
Prevent dehydration Potassium supplementation Potassium sparing diuretics (spironolactone, amiloride) High sodium diet +/- Na supplementation Indomethacin (PGE inhibitor)
Biochem of Barterr’s vs. Gitelman syndrome
Barterr’s syndrome vs. Gitelman’s
Nephrogenic DI etiology
- Congenital
- Secondary
-
Congenital
- X-linked recessive disorder
- Most common pattern of inheritance of inheritance
- Many mutations – commonly mutation in AVPR2 gene (receptor for ADH)
- Autosomal dominant or recessive – 10% of cases
- Males and females equally affected
- Similar clinical phenotype as X-linked disorder
- Mutations in AVPR2 gene also identified
- X-linked recessive disorder
-
Secondary
- Not uncommon – seen in many disorders affecting renal tubular function
- Examples = obstructive uropathies, acute or chronic renal failure, renal cystic diseases, interstitial nephritis, nephrocalcinosis, or toxic nephropathy caused by hypokalaemia, hypercalcaemia, lithium or amphotericin B
- Defective aquaporin expression eg. Lithium intoxication
- Secondary ADH resistance – loss of the hypertonic medullary gradient as a result of solute diuresis or tubular damage resulting in inability to absorb sodium or urea
- Not uncommon – seen in many disorders affecting renal tubular function
Nephrogenic DI key features
Rare congenital or more commonly acquired disorder of water metabolism
Inability to concentrate urine even in the presence of ADH
Clinical manifestation nephrogenic DI
- Congenital
- Secondary
Congenital DI
- Present in newborn period with massive polyuria, volume depletion, hypernatraemia + fever
- Irritability and crying common feature
- Constipation and poor weight gain
- Developmental delay and mental retardation – due to episodes of hypernatraemic dehydratio
- Diminished appetite and poor oral intake – due to need to consume large amounts of water
- Behavioral problems – hyperactivity and ST memory problem
Secondary DI
- Present later in life
- Usually present with polyuria and hypernatraemia
- Associated symptoms such as dev delay and behavioral abnormalities less common
Inheritence + gene affected in congenital nephrotic syndrome (Finnish type)
- Autosomal recessive
- In utero inset of proteinuria
- Gene NPHS1 encodes for nephrin (Finish type)
- Gene NPHS 2 endodes for podocin - most common
- Gene NPHS3 endoce phospholipase epsilon - rare
Nephrogenic DI diagnosis
- Polyuria in a dehydrated child
- Hypernatraemia
- Serum osmolality > 290mOsm/kg with urine osmolality <600mosm/kg
- Lack of response to DDAVP
Treatment of nephrogenic DI
Denys Drash Syndrome
- Nuclear protein (WT1 mutation)
- Autosomal dominant
- Nephrotic syndrome
- Ambiguous genitalia
- Infant onset of steroid resistant nephrotic syndrome
- Wilm’s tumour
Peirson syndrome
- LAMB2 (GBM protein mutation)
- Nephrotic syndrome (mesangial sclerosis)
- Eye problems including microcoria
- Neurological anomalies
Indications for biopsy in nephrotic syndrome
- Atypical presentation or course
- Steroid resistance
- LOW C3
- Age <1yrs or >11yrs
Nephrotic range proteinuria
>3.5g / 24hrs
OR
urine protein: creat ratio > 2
Pentagon of clinical findings with nephrotic syndrome
- Hypoalbuminaemia
- Oedema
- Hypercholesterolaemia (due to increased lipoprotein synthesis by the liver in response to lipid + protein loss in the urine)
- Increased susceptibility to infection (cellulitis, spontaneous bacterial peritonitis + bacteraemia). Particularly encapsulated organisms. Due to loss of IgG + complement in urine.
- Hypercoagulability: vascular stasis, haemoconcentration, intravascular volume depletion, increase plt no, increase hepatic fibrinogen production, loss of antithrombin III + protein S in the urine.
Glomerular lesions associated with idiopathic nephrotic syndrome
Idiopathic nephrotic syndrome = ~90%
- Minimal change disease (85%); glomeruli appears normal or minimal increase in mesangial cells + matrix. Immunofluorescence microscopy negative. 95% respond to steroids.
- Focal segmental glomerulosclerosis
- Membranoproliferative glomerulonephritis
- C3 glomerulopathy
Complications of nephrotic syndrome
- Infection
- Thrombosis
- Hypothryoidism (loss of TGB in urine)
- Hypercholesterolaemia
- Poor growth
- AKI
- Vitamin D deficiency (due to loss in urine)
Treatment of nephrotic syndrome
- Steroids 1st line
- Steroid sensitive IF remision after < 4 weeks treatment
- Steroid dependent IF 2 consecutive relapses whilst on steroids OR within 14 days of ceasing
- Steroid resistant IF failure of remission after at least 4 weeks treatment
IF not responsive then…
- Calcineurin inhibitors (cyclosporine / tacrolimus)
- Rituximab
- MMF
- ACEI to reduce proteinuria
Congenital nephrotic syndrome
Nephrotic syndrome occur within the first 3 months of life
Infantile nephrotic syndrome
Nephrotic syndrome that occurs within the first 3-12 months of life
Kidney anatomy
Glomerulus anatomy
Glomerular filtration barrier
Secondart nephrotic syndrome causes
Minimal chage disease biopsy results
- Immunofluorescence
- Light microscopy
- Electron microscopy
- Immunofluorescence: normal
- Light microscopy: normal
- Electron microscopy: Effacement of epithelial foot processes
FSGS (Focal segmental glomerulosclerosis) biopsy results
- Immunofluorescence
- Light microscopy
- Electron microscopy
- Immunofluorescence: IgM + C3 positive
- Light microscopy: focal sclerotic lesions
- Electron microscopy: foot process effacement
Galloway- Mowat
- Congenital nephrotic syndrome
- Microcephaly
- Hiatial hernia
Is a LOW protein diet recommended in nephrotic syndrome
NO!
What is the strongest genetic factor for SLE?
2nd line treatment of nephrotic syndrome IF steroid resistant
Nephrotic syndrome prognosis
80-90% will respond to steroid treatment (defined as negative / trace urine dipstick for 3 consecutive days)
80% will have a relapse (defined as >3+ protein in urine for 3 consecutive days)
Use of steroids in nephrotic syndrome
Nephrotic syndrome
SSNS
SRNS
SDNS
FRNS
Acute interstitial nephritis vs. acute tubular necrosis
Causes of acute interstitial nephritis
- Drugs (70-75%)
- Antimicrobials
- Anticonvulsants
- Other: allopurinol, diuretics, NSAIDs, PPI
- Infections (5-10%)
- Disease associated
- SLE, acute allograft rejection, TINU (tubulointerstitial nephritis + uveitis)
Definition of tubulointerstitial nephritis
Inflammatory infiltrate in the kidney interstitium
Sparing of glomeurli + blood vessels
Type IV hypersensitivity reaction
Clinical manifestations of tubulointerstitial nephritis
Fever, rash, arthralgia
Rising creatinine
N+V+ fatigue + weight loss
Investigations in acute tubulointerstitial nephritis
What cast is pathognomonic of acute nephritis?
Red cell casts
Dysmorphic red blood cells are pathognomonic of what renal disease?
Glomeular disease
Glomerular histology
What pathology is this photo showing?
Rapidly progressive glomerulonephritis
Biopsy hints for renal disease
What is the most common age range for acute post streptococcal glomerulonephritis?
5-12yrs of agel uncommon <3yrs
Clinical presentation of APSGN
Occurs post Group A beta haemolytic strep infection
- 1-2 weeks post throat infection
- 3-6 weeks post skin infection
Sudden onset haematuria (tea or coca cola coloured), oliguria, HTN, oedema
Malaise, abdo pain, flank pain
Pathogenesis of APSGN
M protein nephritogenic antigens on group A beta haemoytic streptococci strains merge with circulating antibodies –> forms immune complex which deposits on GBM (type III hypersensitivity reaction) —> triggers complement activation + inflammation.
Predicted outcomes in APSGN
- Complications
- HTN + macroscopic haematuria
- Complement
- Proteinuria / microscopic haematuria
- Cure rate
- Relapse
- Complications: PRES, hyperkalaemia, acidosis, seizures, uraemia, encephalopathy
- HTN + macroscopic haematuria: resolves by 1-2 weeks
- Complement normalises 6-8 weeks
- Proteinuria: 6-12 months
- Microscopic haematuria: 1-2 yrs
- 98% resolve completely
- 5% progress to RPGN
- Relapse very unlikely
Investigations for APSGN
- Urinalysis: RBC, RBC casts, proteinuria (some will have protein that is in the nephrotic range), leukocytes
- Complement
- C3 low
- C4 normal (usually)
- Evidence of GAS infection
- throat culture
- Rising antibody titre
- ASOT: positive 3-6 weeks following infection, looking for rising titre
- Rarely elevated post skin infection
- Anti DNAse B antibody
- Positive 6-8 weeks following infection
- Best for testing step pyoderma
- ASOT: positive 3-6 weeks following infection, looking for rising titre
- Biopsy (not routinely performed unless severe or atypical course)
Which of the following is the most sensitive in determine presence of a GAS infection?
- History
- Bacterial culture
- Serology (ASOT / Anti-DNAse B antibody)
Serology (ASOT / Anti-DNAse B antibody)
What are the indications for biopsy in suspected APSGN?
- Severe presentation: acute renal failure
- Atypical course
- Nephrotic syndrome
- Absence of evidence of step infection
- Normal complement levels
- Low complement levels persist for > 2 months
- Persistence of nephritis (haematuria / proteinuria), reduced renal function
APSGN findings on biopsy
IF/IP: starry sky deposits of IgG + C3 deposits along GBM + mesandium
EM: subepithelial humps
LM: glomeruli enlarged + hypercellular
What pathology is this?
APSGN
Starry sky IgG + C3 deposition
What type of hypersenstivity reaction is APSGN
Type III
What pathology is causing this?
APSGN LM: proliferative, capillaries filled with neutrophils. Endothelial + mesangial cell proliferation, increased mesangial matrix.
What pathology is this?
APSGN EM: sub epithelial humps (deposits of IgG + C3)
Management of APSGN
What pathology is this?
IgA nephropahy
What is the main differential diagnosis in suspected APSGN if there is an atypical course with prolonged macroscopic haematuria, proteinuria + no recovery of C3 levels?
MPGN
IgA nephropathy pathognomonic features
- Mesangial deposition of IgA complexes
What is the most common chronic glomerular disease in children?
IgA nephropathy
Secondary causes of IgA nephropathy
- SLE, cirrhosis, celiac, HIV
- All result in elevated circulating IgA
- IgA normally cleared by the liver
IgA nephropathy clinical features
- M>F
- Synpharyngitic macroscopic haematuria (most common)
- Within 1-2 days of onset of infection
- Often renal anlge pain
- Asymptomatic microscopic haematuria
- Acute nephritis= haematuria, proteinuria, renal failure, HTN
- Nephrotic syndrome (rare < 10%)
What does this LM slide show?
IgA nephropathy.
- A, In IgA nephropathy, segmental areas (arrows) of mesangial hypercellularity and matrix expansion occur, characteristic of mesangioproliferative glomerulonephritis. Part of the glomerular tuft adheres to Bowman’s capsule (white dashed oval), constituting the starting point of a secondary focal segmental glomerulosclerosis lesion. Tubulointerstitial damage with leucocyte infiltrates, tubular atrophy and fibrosis (arrowhead), and tubular protein casts (asterisk) is also present. PAS stain.
- B, Other glomeruli in the same patient exhibit few pathologic abnormalities on light microscopy (PAS stain), but the characteristic mesangial granular IgA deposition (C) can be found in these glomeruli as well.
Investigations in IgA
- NORMAL complement
- Serum IgA is of NO value (only elevated in 15% of paediatric patients)
- Biopsy results
- LM: focal + segmental mesangial proliferation
- IF: large, globular IgA deposition in mesangium
- MESTC criteria
- Mesangial hypercellularity
- Endocapillary hypercellularity
- Segmental glomerulosclerosis
- Tubular atrophy/ interstitial fibrosis
- Crescents
- MESTC criteria
Management of IgA nephropath
Key = BP control + management of proteinuria
- Antihypertensives: ACEI + ARB
- Immunosuppression (steroids) may be useful in severe disease
IgA nephropathy prognosis
- Complete remission more likely in children
- 20-30% will develop ESKD in 15-20 yrs
- Features associated with ESKD
- Hypertension
- Reduced renal function
- Prolonged proteinuria
- Biopsy: glomerulosclerosis >20%, tubular atrophy, interstitial fibrosis
NO bearing on prognosis: persistence / no. of episodes of haematuria
IgA nephropathy vs. HSP
EXACTLY same features on renal biopsy
Although immune complexes large in HSPN
How common in HSP nephritis?
50% of patients with HSP develop some form of nephritis
97% will develop their nephritis within 6 months
Poor prognostic factors in HSPN
- Nephritic / nephrotic range at presentation
- Persistent / progressive proteinuria (>3 months)
- Older age
- Recurrence
- Necrosis or cresenteric changes
HSP nephropathy screening
Review clinically + check BP + early morning urinalysis
- Weekly 1st month
- Fortnightly month 2- 3
- 6 month mark
- 12 month mark
IF no significant renal involvement + normal urinalysis at 12 months no further follow up is required
Causes of acute glomerulonephritis
Pathophysiology of SLE associated nephritis
Mediated by immune complexes
- Mesangial/ subendothelial deposits = large complexes, negatively charged, proliferative (nephritis)
- Subepithelial deposits = native Ag-immune complexes, less inflammatory, result in membranous nephropathy with nephrotic features
Classification of SLE nephritis
Class I = minimal mesangial lupus nephritis (deposits on IF/EM only)
Class II = mesangial proliferative nephritis
Class III and IV = mesangial and endocapillary lesions (‘wire loop lesions’) à MOST COMMON
Class V = membranous lupus nephritis
Class VI = advanced sclerosing
Chronic = tubulointerstitial nephritis
Treatment of SLE nephritis
Regular urine screen for evidence of nephritis
Class I + II - no specific treatment; good prognosis
Class III-V - require treatment
Immunosuppression – goal:
- Clinical remission = normalization of renal function and proteinuria
- Serological remission = normalization of anti-DNA antibody, C3 and C4 levels
Treatment
- Initiation = combination of prednisolone, pulse IV methylprednisolone, cyclophosphamide
- Maintenance = combination of MMF, AZA, cyclophosphamide, rituximab
- Other treatment options = plasmapheresis – only considered if accompany TTP or ANCA disease
- Relapsing/resistant disease = consider MMF, cyclophosphamide, rituximab
Adjunctive
- ACE-I
- Statin
Other immunomodulators = hydroxychloroquine (joint, skin, relapse prevention)
Biopsy findings for SLE nephritis
Granular deposits of ALL immunoglobulin isotyopes (IgG, IgM, IgA) + complements (C3, C4, C19)
Criteria for nephrotic syndrome
Proteinuria >3.5g / 24hrs OR >40mg/m2/hr
Urine Pr/Cr > 2
What is PR3 ANCA associated with?
GPA (Granulomatous polyangitis) = Wegner’s
cANCA (cytoplasmic) = PR3 ANCA
Granuloma upper + lower respiratory tract infections (common) + kidneys (rare)
What is MPO pANCA associated with?
MPA = microscopic polyangitis
NO granuloma
Can have respiratory involvement (pulmonary capillaritis- can haemorrhage), intersitial lung disease
NOT usually chronic rhinosinusitis (which is seen in GPA)
ANCA vasculitis pathophysiology
Ab directed against neutrophil cytoplasmic Ag
Infectious triggers exposes PR3 or MPO epitopes
LMW proteinuria is the hallmark of ______ nephropathy
Proximal tubular nephropathy
What does urine protein electrophoresis do?
Can differentiate between glomerular + proximal tubular nephropathy
What are the insensible losses of
- Older children
- Neonates/ infants
- Older children: 400mL/m2/day
- 20-50mL/kg/day
Causes of Fanconi syndrome (most common by age)
- Cystinosis in the MOST common
Low/high sodium is a disorder of _______ of which _____ is the main physiological mediator.
Normally _______ keeps our sodium and osmolarity in the normal range ______
Urine osm varies from _____ mOsm/L
Low/high sodium is a disorder of WATER of which ADH is the main physiological mediator.
Normally THIRST keeps our sodium and osmolarity in the normal range 275-295
Urine osm varies from 50-1200 mOsm/L
Calculation for sodium deficit
0.6 x weight x (Na desired - Na actual)
What is the maintenance sodium rate?
2-4mmol / kg/day
At what rate do you want to correct hyponatreamia?
Less than 0.5mmol/L/hr and <8mmol/l/day
What are the key features of Alport syndrome
- Chronic kidney disease
- Sensorineural hearing loss
- Ocular abnormalities
- Anterior lenticonus or dot and fleck retinopathy
- Leiomyoma rare (2-5%)
**Eye + ear abnormalities more common with X-linked Alport syndrome**
Alport genetics
Autosomal recessive polycystic kidney disease manifestations
Who am I?
2yr old boy presents with ataxia, hypotonia, developmental delay
MRI brain is performed which reveals…..
JOUBERT SYNDROME
- Autosomal recessive
- Clinical manifestations
- Key TRIAD
- Cerebellar + brain stem malformation = molar tooth sign (vermal aplasia) —> ATAXIA
- Hypotonia
- Developmental delay
- Other features
- Eye: coloboma, retinitis pigmentosa, nystagmus
- Irregular breathing
- Renal abnormalities = cystic disease
- Polydactyl
- Hormone abnormalities
- Key TRIAD
Dent’s disease
- Inheritence
- Genes
- Clinical features
- X-linked recessive nephrolithiasis
- Present with polyuria, microscopic haematuria, proteinuria or kidney stones. 75% of patients develop kidney stones.
- Most cases of Dent disease are caused by mutations in the CLCN5 gene that inactivates a voltage-gated chloride transporter named CLC-5. S
- ome cases are associated with mutations in the OCRL1 gene, which is also the gene mutation associated with Lowe oculocerebrorenal syndrome.
Cystinosis
- Disease
- Pathophysiology
- Investigations
- Presentation
- Cystinosis is a lysosomal storage disease.
- Cysteine accumulates in organs and tissues, leading to severe organ dysfunction.
- Children appear normal at birth but present with renal problems at 3-6 months of age.
- They will often have vitamin D resistant rickets at presentation, secondary to phosphate wasting.
- Diagnosis is confirmed by measuring high levels of cysteine in leukocytes or fibroblasts.
- Homocystinuria is a different entity but is often confused with cystinosis because of the similar name. Children with homocystinuria have Marfanoid habitus and are prone to thrombotic events but do not usually have renal problems.
