METABOLIC DISEASE PATHOLOGY

CHAPTER 15 METABOLIC DISEASE PATHOLOGY




Approach to metabolic disease pathology

Organic acidemias

Disorders of amino acid metabolism

Urea cycle defects

Fatty acid oxidation disorders

Lactic acidemias

Disorders of carbohydrate metabolism

Peroxisomal disorders

Purine metabolism disorders

Transport pathway disorders

Mucopolysaccharidoses

Mucolipidoses

Lipid storage disorders

Batten disease (neuronal ceroid lipofuscinosis)


APPROACH TO METABOLIC DISEASE PATHOLOGY



Overview (Nyhan et al 2005)



• Metabolic disease can have a wide range of clinical presentation throughout the pediatric age range
image often in early life

image mixture of
– neuromuscular disorders

– failure to thrive

– acute exacerbations
· may be precipitated by infections

• Definitive diagnosis is often based on clinical, biochemical, genetic and pathological findings
image often specific biochemical and enzymological tests
– require blood and/or fresh tissue

– enzyme analysis of fibroblast cultures

• Many disorders have non-specific histological features

• Surgical pathology samples are not part of routine investigation for most metabolic diseases
image encountered mainly in the following settings:
– for primary diagnosis of metabolic disease
· rare

– for further investigation of suspected disease
· often bone marrow or liver biopsy

image screening for metabolic disease
– see chapter 19 regarding hair and blood samples

image other indications
– incidental in patients with metabolic disease

• Many disorders are discussed in the appropriate organ-specific chapters

• This chapter provides only the main features relevant to a diagnostic histopathologist who encounters a surgical pathology specimen in a child with suspected metabolic disease
image full details of biochemical and genetic findings are not included

image autopsy findings are not included
– only included here are samples which may be encountered in surgical pathology practice


ORGANIC ACIDEMIAS



• Present with metabolic acidemia / aciduria
image many with lactic acidemia

• Variety of pathways affected

• Rarely associated with specific histopathological features

• Methymalonic acidemia
image hepatomegaly

image non-specific tubulointerstitial nephritis


DISORDERS OF AMINO ACID METABOLISM



• Most do not have characteristic histological findings
image present with mental retardation and other features

• Tyrosinemia (fumarylacetoacetate hydrolase deficiency)
image infantile cirrhosis (see liver chapter; Prive 1967, Carson et al 1976, Russo 1990)
– development of hepatocellular carcinoma

image may develop hypertrophic cardiomyopathy


UREA CYCLE DEFECTS



• Most present with neonatal coma
image hyperammonemia

• Liver biopsy and enzyme analysis may be carried out
image non-specific morphological features

• Argininosuccinic aciduria
image trichorrhexis nodosa

image hepatomegaly

• Lysinuric protein intolerance
image diarrhea with villous atrophy

image acrodermatitis
– may resemble celiac disease clinically

image some show bone marrow changes
– sea-blue histiocyte-like cells

– erythrophagocytosis

image lung pathology
– interstitial fibrosis

– cholesterol crystals / granulomas

image liver pathology
– normal

– variable fatty change

– cirrhosis


FATTY ACID OXIDATION DISORDERS



• Diagnosis by tandem mass spectrometry and biochemical / enzyme and genetic confirmation

• Variable presentation:
image sudden infant death

image cardiomyopathy

image Reye-like syndrome

• Non-specific histological findings
image liver biopsy shows microvesicular and/or macrovesicular

image muscle biopsy is either normal or shows fat accumulation

• Electron microscopy
image liver and/or muscle fat accumulation

image may show abnormal mitochondria and peroxisomes

• Multiple acyl CoA dehydrogenase deficiency (Glutaric aciduria type II)
image as above

image syndromic type polycystic kidneys

image cortical dysplasias and heterotopias


LACTIC ACIDEMIAS



• Complex group

• Lactic acidemia may be secondary to other metabolic disorders
image especially with intercurrent stress or infection

• Primary lactic acidemias disorders of pyruvate metabolism

• Some due to nuclear or mitochondrial DNA defects

• Some no identifiable cause

• Variable presentations:
image acute lactic acidosis

image ataxia

image myopathy

image Leigh syndrome (subacute necrotizing encephalomyelopathy)
– autopsy diagnosis

• Variability in part due to heteroplasmy in mitochondrial diseases

• Muscle biopsy may be performed
image morphology

image mitochondrial structure / function

image DNA extraction

• In addition to these features specific histological findings include:
image myoclonic epilepsy and ragged red fibers
– multiple lipomas neck / trunk

image Pearson syndrome
– infantile anemia and pancytopenia
· hypercellular marrow

· vacuolated precursors

· ring sideroblasts

image mitochondrial depletion syndromes
– cirrhosis, cholestasis, steatosis, hemosiderosis

– pleomorphic mitochondria on electron microscopy:
· Alpers’ syndrome:

· neurological symptoms

· episodes of decompensation

· liver changes as above

· additional neuropathological changes (autopsy)


DISORDERS OF CARBOHYDRATE METABOLISM



• Galactosemia
image vomiting, jaundice, hepatomegaly, FTT, cataracts, mental retardation
– may present with E. coli neonatal sepsis

image histological specimens most often liver biopsy (see chapter 10)

• Glycogen storage diseases
image group characterized by abnormal metabolism of glycogen and
– deposition of glycogen in tissues

– hypoglycemia and ketosis (variable)

image histological specimens most often liver biopsy (see chapter 10)

image Type I – Von Gierke Disease
– neonatal liver biopsy may be normal

– hepatic adenomas may develop

image Type II – Pompe
– lysosomal storage disease with alpha-glucosidase deficiency
· membrane bound lysosomal glycogen storage

– cardiomyopathy with cardiomegaly

– skeletal myopathy

– vacuolated lymphocytes (Figs 15.1, 15.2) (see chapter 10)

image Type III – debrancher deficiency
– hepatomegaly

– myopathy

image

Fig 15.1 Photomicrograph of blood film showing lymphocyte vacuolation in Pompe disease.


image

Fig 15.2 Photomicrograph of blood film showing lymphocyte vacuolation in Pompe disease. (PAS)



PEROXISOMAL DISORDERS


(Roels et al 1991, 1993, Dimmick et al 1993, Powers 1995)



• Neonatal adrenoleukodystrophy

• Zellweger

• Many others now recognized

• Present with:
image hypotonia

image seizures

• Liver biopsy
image periportal fibrosis

Related posts:

  1. BONE PATHOLOGY
  2. HEAD AND NECK PATHOLOGY
  3. RENAL PATHOLOGY
  4. TUMORS AND TUMOR-LIKE LESIONS

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Jun 18, 2016 | Posted by in PEDIATRICS | Comments Off on METABOLIC DISEASE PATHOLOGY

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