Thursday, April 20, 2017

- Urine analysis Differentiation between Golmeular and Non-Glomerular hematuria

 Urine analysis Differentiation between
 Golmeular and Non-Glomerular hematuria



Golmeular
Non-Glomerular
Colour
brown, smoky, cola-colored, or tea-colored as a result of the hematin formation from hemoglobin in the acidic environment.
bright red or pink
RBCs morphology
Dysmorphic > 80%
Acanthocytes > 5%
Normal
proteinuria
>100 mg/dL via dipstick,
minimal proteinuria
on dipstick (<100 mg/dL).
Clots
Absent
May be Present
RBCs cast
May be present due to squeezing of RBCs and sticking together and entangled in the protein matrix
Absent
Pain
Painless
Painful

Sunday, April 16, 2017

- Multifactorial inheritance (polygenic inheritance).

Multifactorial inheritance (polygenic inheritance)
 

Result from the interplay of genetic and environmental factors.

There is a similar rate of recurrence among all 1st-degree relatives (parents, siblings, offspring of the affected child). It is unusual to find a substantial increase in risk for relatives related more distantly than 2nd degree to the index case.

The magnitude of the trait is determined by number of genes (each adding a small amount to the quantity of the trait or subtracting a small from it)

Also number of environmental factors each act by adding or subtracting an amount to final result. 

Conditions often associated with multifactorial inheritance:

Congenital malformations:
      neural tube defects
      congenital heart disease
      cleft lip and palate
      pyloric stenosis
      developmental dysplasia of the hip (DDH)
      talipes equinovarus
      hypospadias

Thursday, April 13, 2017

- Factors affecting gene expression (in AD disorders)



Factors affecting gene expression
 
 (in Autosomal dominant disorders)


1.     Pleiotropy
2.     Variable expressivity
3.     Reduced penetrance
4.     New mutations
5.     Homozygosity
6.     Knudson two-hit hypothesis
Pleiotropy
·        A single gene (AD) that may give rise to 2 apparently unrelated effects.
·        In tuberous scelerosis, some affected individuals may have all features (learning difficulties, epilepsy, facial rashes,…)
·        Pleiotropy can result from different mutations in the same gene
·        AD traits may involve only one organ of the body i.e. the eye in congenital cataract. 
Variable expressivity  
·        Striking variation in the clinical features of AD disordes from person to person , even in the same family.
·        In AD polycystic kidney disease, some affected individuals develop renal failure in early adulthood whilst others have just a few renal cysts without affection of renal function.
Reduced Penetrance
·        Penetrance describes the frequency with which phenotypic manifestation of a gene are expressed.
·        A highly penetrant gene (100% penetrance) will express itself almost regardless of the effect of the environment or other interacting gene.
·        This phenomenon explains apparent skipped generations in certain pedigrees.
·        Reduced penetrance when the gene produces characteristic features much less often.
Factors Affecting Penetrance:
1.     Modifier genes.
2.     Hormonal/ reproductive factors.
3.     Response to DNA damage.
4.     Carcinogens (Not everyone with an altered gene develops cancer).

Monday, April 10, 2017

- The Syndrome of Pyogenic Arthritis with Pyoderma Gangrenosum and Acne.



The Syndrome of Pyogenic Arthritis with Pyoderma Gangrenosum and Acne

PAPA syndrome is a rare autosomal dominant disorder caused by mutations in PSTPIP1, a gene located on chromosome 15 that encodes the cytoskeletal proline serine threonine phosphatase-interacting (PSTPIP) protein. 

Clinical manifestations:

  • Recurrent episodes of sterile, pyogenic arthritis that leads to erosions and joint destruction, and appears to develop spontaneously or after minor trauma. The onset of arthritis is often in early childhood.
  • Cutaneous manifestations tend to develop in adolescence, at which time patients are prone to developing severe cystic acne.
  • PAPA patients commonly develop ulcerating pyoderma gangrenosum lesions  and some develop pathergy reactions

Thursday, April 6, 2017

- PERIODIC FEVER, APHTHOUS STOMATITIS, PHARYNGITIS AND ADENITIS (PFAPA).



PERIODIC FEVER, APHTHOUS STOMATITIS, PHARYNGITIS AND ADENITIS (PFAPA)

PFAPA is the commonest periodic fever syndrome in childhood.
It usually presents between the ages of 2 and 5 yr.
It is unlikely to be due to a single gene .

Diagnosis:
Diagnosis is clinical, in the absence of evidence of infections or cyclic neutropenia:

  • Regular recurrent fever of early onset.
  • Oral aphthous ulcers.
  •  Cervical lymphadenopathy.
  • Pharyngitis.
  •  less commonly, headache, abdominal pain, and arthralgia.

The episodes last 4-6 days, regardless of antipyretic or antibiotic treatment, and often occur with clock-like regularity on 3-6 wk cycles.
Children are in a good health between episodes.
Fever cycles usually stops by the teenage years.

Tuesday, April 4, 2017

- Cryopyrin-associated periodic syndromes.



Cryopyrin-associated periodic syndromes (CAPSs)
CAPS includes a spectrum of conditions ranging from mild to severe, and includes three syndromes:

  • FCAS.
  •  MWS.
  • CINCA/NOMID.

INCIDENCE/AETIOLOGY:
CAPS is extremely rare, with an incidence of probably <1 in 500,000.
CAPS is due to mutations in NLRP3/CIAS1 on chromosome 1q44, that encodes the key component of IL-1 activation complex: the inflammasome.
A dominant inheritance occurs in about 75% of patients with FCAS and MWS, whereas CINCA is usually due to de novo mutations 
.
CLINICAL PRESENTATION:-
Onset is in early infancy, often from birth; there is no sex bias.
Children present with a characteristic appearance of flattened nasal bridge and bossing of the skull.

  •  FCAS: attacks of fever generally begin 1-3 hr after generalized cold exposure, urticarial rash, arthralgia and conjunctivitis, episodes are self-limited and generally resolve within 24 hr.
  • MWS: daily attacks (afternoon/evenings), Acute symptoms include fever, urticarial rash, arthralgia and myalgia, conjunctivitis, headache and fatigue.Rash can be persistent.Deafness occurs later and is often missed in the early stages.
  • CINCA/NOMID: continuous inflammation with additional severe chronic aseptic meningitis, raised intracranial pressure, uveitis, deafness and arthropathy.

Sunday, April 2, 2017

- Hyperimmunoglobulinemia D with periodic fever syndrome.



Hyperimmunoglobulinemia D with periodic fever syndrome (HIDS)
/ Mevalonate kinase deficiency (MKD)


INCIDENCE/AETIOLOGY
MKD/HIDS is extremely rare. Most patients are North European, many in Holland (it was called Dutch fever’), but can occur in other ethnicities.
The disease is caused by mutations of MVK, a gene located on the long arm of chromosome 12 that encodes mevalonate kinase (MK).

CLINICAL PRESENTATION

  • Onset of MKD/HIDS within the 1st 6 mo of life.
  • Children experience irregular attacks that may be precipitated by vaccination, minor trauma, surgery or stress.
  • Attacks last 4–7 days.
  •  Fever, unilateral or bilateral cervical lymphadenopathy, abdominal pain with vomiting and diarrhea, headache, arthralgia, large joint arthritis, erythematous macules and papules and aphthous ulcers are common.
  • A history of high fevers or a full attack with vaccination is often obtained