Virginia C. Espinosa Navarro

Juan R. Gaviria García

Support the witness of the internal wayopposite to all the circumstances that couldalter it.

Kidney Stabilizes the volume and thephysicist – chemistry caharacteristics of theLEC and LIC.

Sodium, potassium, chloride andbicarbonate.

Eliminates the excess of water, electrolytes,osmoles, metabolic products of waste andthe toxic products.

INTRODUCTION

• Decrease reabsorption of electrolytes and nutrients in the blood torrent.

• Clinical characteristics:

Poliuria, polidipsia and dehydration

. Hypophosphate

mic, rickets, osteomalacia

Phosphaturia, Glucosuria, Proteinuria,

Hyperuricosuria

Decrease of thegrowth, acidose, hipopotasemia, hyperchloremia

FANCONI’S SYNDROME

Cellular organela with a membraneconstituted by a double lipid layer.

Proteins of enzymatical function.

Liver, kidney, brain (formation of themyelin).

Lipid metabolism: fatty acid of very longchain beta-oxidation, plasmalogenformation, cholesterol and billiary acids.

PEROXISOMAS

EHHADH

The protein bifunctional enzyme.

Enzymes of the peroxisomal beta-oxidationpathway.

The N-terminal enoyl-CoA hydrataseactivity.

The C-terminal region contains 3-hydroxyacyl-CoA dehydrogenase activity.

Peroxisomal disorders.

RELATION

Identify the molecular, biochemical,

and cellular defects that result in

impaired renal tubular reabsorption.

GENERAL OBJECTIVE

MATERIALES Y

MÉTODOS

PACIENTES

ESTUDIOS GENÉTICOS

Extracción del ADN:1. Lisis celular.

2. Extracción de lípidos de membrana.

3. Extracción de proteínas mediante la adición de

una proteasa.

4. Precipitar el ADN con un alcohol.

Análisis de ligamiento de

multipunto

Secuenciación: determinación del orden

de los nucleótidos. MÉTODO DE SANGER.

LÍNEA CELULAR

LLC-PK1 Mutación EHHADH

EHHADH Oxidación

peroxisomal de ácidos grasos.

Transporte de fluído (túbulo

proximal).

Función respiratoria

mitocondrial.

INMUNOPRECIPITACIÓN

HADHA Y HADHB

Anti - HADHB

KNOCKOUT

Función bioquímica de

EHHADH

Fosfato urinario y

metabolitos urinarios

Estudios óseos (45 – 51

semanas de edad).

RESULTADOS

Autosómica

Dominante

1-74 años

RESULTADOS

Niña afectada de 12

años.

Raquitismo y

crecimiento disparejo

por pérdida renal de

fósforo.

RESULTADOS

Excreción

urinaria de

proteínas de 1.2

g por día.

RESULTADOS

RESULTADOS

LLC-PK1:

Sin mutar en mitocondria

Mutada en mitocondria y peroxisoma

Cos-7 y HEK293

No anormalidades morfológicas

RESULTADOS

Cromosoma 3q27

RESULTADOS

D3S3583

D3S2747

RESULTADOS

Mutación por cambio de

sentido(p.E3K)

Glutamato → Lisina

25 aminoácidos

RESULTADOS

Fosforilación

Oxidativa

Capacidad de

Transporte

Anticuerpo

Anti-HADHB

RESULTADOS

Ratones Knockout:

No aminoaciduria oglucosuria

Valores normales deintermediariosenergéticos yglagolíticos en orina

La ausencia del genno tiene un efectosignificante.

RESULTADOS

DISCUSIONAuthor Idea Yes/No

19. Kleta R, Bockenhauer D. Renal Fanconi’s syndrome

comprises a heterogeneous

group of disorders

characterized by proximal

tubular dysfunction leading to

generalized

aminoaciduria, glucosuria,

phosphaturia, lowmolecular-

weight proteinuria, and

metabolic acidosis

due to renal bicarbonate

losses.19

Yes

25. Balaban RS, Mandel LJ. Remarkably, proximal tubular

cells do not

use glucose for their energy

production25; fatty

acid oxidation is the

predominant energy source.

Yes

DISCUSION

Author Idea True/False

29. Houten SM, Denis S,

Argmann CA, et

al.

Despite these known roles of L-

PBE in peroxisomal

oxidation pathways, it plays a

minor role

in overall fatty acid oxidation

and energy production,

as indicated by the fact that

Ehhadh knockout

mice are viable and ostensibly

unaffected.29

Yes

31. Koopman WJ, Willems PH,

Smeitink JA.

The findings in this family

indicate that a

monogenic defect leading to

intracellular mistargeting

of a mutant protein can result in

mitochondrial

damage and isolated organ

disease

— in this case, renal Fanconi’s

syndrome.31

Yes

CONCLUSIONS

Energy requirements are very important

because, many process in our bodies required

them and if they are deficient, it can cause a

very life-threatening damage like this

syndrome.

CONCLUSIONS

A mutation in some

genes of a protein

makes them more

related to the

subunits of other

enzyme complex that

they weren´t used to

work with.

CONCLUSIONS

Haploinsufficiency of genes are less

aggressive than a mutation, cells could

continue working if some proteins won´t be

expressed.

CONCLUSIONS

Sometimes many

syndromes won´t be

studied because they

appear as a part of a

multisystem

metabolic disease,

ignoring that they

could have a

genomic component.

Mapa conceptual

Virginia Espinosa

Mapa Conceptual Juan Ricardo

Gaviria G.