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TitleHutchison Paediatrics
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Total Pages904
Table of Contents
                            Front Matter
	Cover
	Contributors
	Foreword
	Preface to the Second Edition
	Preface to the First Edition
Contents
1. Paediatric History and Examination
2. Growth and Development
3. Neonatal Paediatrics
4. Paediatric Genetics
5. Nutrition
6. Respiratory Disorders
7. Gastroenterology and Hepatology
8. Paediatric Cardiology
9. Care of the Paediatric Surgical Patient
10. Neonatal Surgery
11. General Paediatric Surgery
12. Paediatric Urology
13. Paediatric Oncology
14. Dermatology
15. Haematological Disorders
16. Paediatric Rheumatology
17. The Urinary System
18. Diseases of Nervous System
19. Accidental Poisoning in Childhood
20. Metabolic Diseases
21. Endocrine Disorders
22. Paediatric Orthopaedics
23. Paediatric Dentistry
24. Immunity and Allergy
25. Immunisation Against Infectious Diseases
26. Infectious Diseases
27. Paediatric Ophthalmology
28. Haematological Investigations in Children
29. Biochemical and Microbiological Investigations in Paediatrics
30. Paediatric Emergencies
31. Disorders of Emotion and Behaviour
32. Paediatric Radiology
33. Paediatric Maxillofacial Surgery
34. A Prescription for Play
35. Paediatric Rehabilitation
36. Prescribing for Children
37. Child Abuse and Neglect-How do We Protect these Children
38. Practical Paediatric Procedures
Appendices
Index
                        
Document Text Contents
Page 2

HUTCHISON’S
PAEDIATRICS

Page 452

Hutchison's Paediatrics 432432

inheritance in Leigh syndrome, which suggests that it may be
caused by a nuclear gene rather than a mitochondrial defect.
However, in some patients mutations have been found in
mtDNA. There are some patients who do not fit into these
clinical patterns of disease and many have been shown to
have multiple defects of respiratory chain complexes due to
mtDNA disorder.
Leber hereditary optic neuropathy (LHON) is one of the
commonest inherited causes of blindness in young men due
to a disorder of mtDNA. Some men with the disorder have
an encephalopathy with deafness and dystonia and a few
develop cardiac conduction defects. There is some evidence
that a gene on the X-chromosome may be linked with this
disorder.
There are a variety of syndromes with non-neuromuscular
presentation, which involve the gastrointestinal tract with
anorexia and vomiting and occasionally hepatic failure; yet
others have cardiomyopathy with different degrees of heart
block, renal disease with generalised aminoaciduria and
haematological disorders affecting bone marrow function. In
Pearson syndrome, which presents at birth or early infancy
there is refractory sideroblastic anaemia, thrombocytopenia,
neutropenia, metabolic acidosis, pancreatic insufficiency
and hepatic dysfunction. Renal tubular disorder, diarrhoea,
steatorrhoea and skin lesions with eventual liver failure have
been described. Deletions of mtDNA have been identified.
Many of the respiratory chain disorders may present in the
very young but there are three specific syndromes affecting
the infant. The first is fatal infantile lactic acidosis. Infants
present with hypotonia, vomiting and ventilatory failure
and die often before the age of 6 months. A generalised
aminoaciduria (de Toni-Fanconi-Debré syndrome), grossly
increased plasma lactate concentrations, hypoglycaemia,
liver dysfunction, convulsions and increased plasma calcium
have been reported. The second clinical presentation is
benign infantile lactic acidosis, which may present with
failure to thrive, respiratory failure and hypotonia with
increased plasma lactate concentrations but the condition
gradually remits and by 12–18 months these infants are often
normal. There is a cytochrome oxidase defect, which appears
to improve with age and may be related to a switch from a
fetal to an adult form of complex IV. The third syndrome is
the mtDNA depletion syndrome in which the infant is weak,
hypotonic and has respiratory difficulties together with renal
tubular disorder and convulsions. The condition is usually
fatal before the age of 1 year.

Treatment
Children with respiratory chain defects have been treated
with vitamin C (4 g/day), vitamin K (menadione: 50 mg/day)
and ubiquinone (100 mg/day) in the hope that these vitamins

may act as artificial electron acceptors. Some improvement
in electron transfer has been suggested by nuclear magnetic
resonance (NMR) studies in these patients but there is some
doubt as to the overall clinical benefit. Other treatments
have included thiamine, biotin, L-carnitine, riboflavin
and dichloracetate. As the mitochondrial respiratory chain
generates free radicals, scavengers such as vitamin E might
be of some clinical benefit. Unfortunately most of these
conditions are progressive and result in significant disability
and/or death. Considerable support of the families involved
is required during the care of these infants and genetic
counselling with prenatal diagnosis is available for some of
these conditions.

PEROXISOMAL DISORDERS
Peroxisomes are present in every body cell except the mature
erythrocyte and are particularly abundant in tissues active
in lipid metabolism. They do not contain DNA and are,
therefore, under the control of nuclear genes. Peroxisomes
have a number of metabolic functions—particularly:
a. Fatty acid β-oxidation of very long-chain fatty acids

(VLCFAs), pristanic acid and cholestanoate compounds
which are intermediates in biosynthesis of bile acids

b. Plasmalogen synthesis
c. Phytanic acid oxidation—a branch-chain fatty acid

formed from chlorophyll metabolism, and
d. Glycolate detoxification preventing formation of oxalate.
Over sixteen clinical and biochemical disorders have
now been ascribed to disorders of peroxisomal metabolic
functions.
Table 20.2 gives a tentative classification of the
peroxisomal disorders. In the group l disorders, there
is a reduction or absence of functional peroxisomes.
Zellweger syndrome is a lethal disease presenting with
severe hypotonia, typical craniofacial abnormality with
a high domed forehead, severe developmental delay
with neurosensory defects and progressive oculo-motor
dysfunction. These neurological abnormalities may be
related to the neuronal migration disorders found in the brain
at post-mortem. There is also progressive liver dysfunction
with chondrodysplasia calcificans of the patellae and the
acetabulum. In neonatal adrenoleukodystrophy (ALD), there
is progressive demyelination of the cerebral hemispheres,
cerebellum and brainstem with neuronal migration
disturbances and perivascular lymphocytic infiltration.
There is also adrenal atrophy. In infantile Refsum disease
(IRD), there is developmental delay, retinitis pigmentosa,
failure to thrive and hypocholesterolaemia. In the group 2
disorders, rhizomelic chondrodysplasia punctata (RCDP)
is an autosomal recessive disorder characterised by short
stature, a typical facial appearance, joint contractures and

Page 453

 Metabolic Diseases 433

Table 20.2: Classification of peroxisomal disorders

1. Peroxisome deficiency disorders
• Neonatal adrenoleukodystrophy
• Infantile Refsum disease
• Hyperpipecolic acidaemia

2. Disorders with loss of multiple peroxisomal functions and
peroxisome structure in fibroblasts
• Rhizomelic chondrodysplasia punctata
• Zellweger-like syndrome

3. Disorders with an impairment of only one peroxisomal function
and normal peroxisomal structure
Disorders of peroxisomal β-oxidation:
• Adrenoleukodystrophy (X-linked) and variants
• Acyl-CoA oxidase deficiency
• Bi (multi) functional protein deficiency
• Peroxisomal thiolase deficiency
Other disorders:
• Acyl-CoA: Dihydroxyacetonephosphate acyltransferase

(DHAPAT) deficiency
• Primary hyperoxaluria type I
Acatalasaemia
• Glutaryl oxidase deficiency

X-ray changes showing stippling of the epiphyses in infancy
and severe symmetrical epiphyseal and extra-epiphyseal
calcifications in later life. Only few patients have been
described as having the Zellweger-like syndrome which is
clinically indistinguishable from the classical Zellweger but
shows abundant peroxisomes in the liver. In the group 3
disorders with impairment of a single peroxisome function
and with a normal peroxisome structure ALD, an X-linked
recessively inherited disorder, usually affects males between
the ages of 4 and 10 years.
Initially there may be attention deficit noticed in school
followed by convulsions, visual disturbance with the later
manifestations of paralysis and death. This phenotype
known as childhood ALD has been treated with long-chain
polyunsaturated fatty acids but there is some doubt as to the

overall benefit of this form of therapy. About 25% of ALD
cases present in adulthood with paraparesis whilst a few may
exhibit adrenocortical insufficiency without neurological
involvement. About 20% of female heterozygotes develop
mild or moderate progressive paraparesis after the age of 40
years.
The other disorders are also rare apart from primary
hyperoxaluria type I, an autosomal recessive disorder of
glyoxylate metabolism, in which there is recurrent calcium
oxalate nephrolithiasis and nephrocalcinosis presenting
during the first decade. There are a few, however, who
present with an acute neonatal form of the disorder and early
death.

Treatment
Apart from the attempt to treat X-linked ALD with fat
restriction and supplementation with glycerol trioleate
and glycerol trierucate, which has been shown to improve
peripheral nerve function, but not as yet to effect long-
term benefit there are recent reports that bone marrow
transplantation may be effective in mildly affected childhood
ALD patients. In more advanced X-linked ALD, bone
marrow transplantation worsened the clinical picture. It is
hoped that gene therapy might improve the outlook for this
condition. Treatment with pyridoxine may be effective in a
small number of patients with primary hyperoxaluria type
I. Haemodialysis may be required during end-stage renal
failure in this disease and surgical removal of oxalate stones
may be required. Eventually combined liver and kidney
transplant becomes necessary for survival.

CONCLUSION

Although individual inherited metabolic diseases are rare
and this book contains only a limited review of some of
the disorders, collectively they form a major grouping of
disorders causing significant mortality and an overwhelming
burden of morbidity for families and the community.

Page 903

 Index 883

synovitis 482
tachypnoea of newborn 34, 662
transillumination 842
translation 70f
transport 638
transportation of patients 188
transposition of great arteries 171, 171f, 184
trapping 659f
trauma score 197t
traumatic
acquired spinal cord injury 775
retinopathy 594, 594f
tap 615
ulceration 491
travel immunisation 532
treacher collins syndrome 736, 736f
treat/prevent
dehydration 79
hypoglycaemia 78
hypothermia 79
infection 79
treatable disorders 414
treating joint instability 475
treatment
for thyroglossal duct cyst 233
treatment of
corneal opacities in childhood 584
DDH
between age of 6 and 18 months 471
in children between 18 months and 3

years 471
infants under 6 months of age 470
hepatic disorders 147
high-risk disease 265
initial presentation of idiopathic nephrotic

syndrome 343
intermediate risk disease 265
juvenile
dermatomyositis 333
idiopathic arthritis 327
low-risk disease 265
neonatal
hip instability 470
meningitis and sepsis 55t
ulcerative colitis and crohn disease 136
tricuspid atresia 172, 172f, 185
tripod pinch 773f
trisomies 65t
truancy 649
truncus arteriosus 673
trunk control 766f
tryptase 523f
tube malposition 662
tuberculoma 695f
tuberculosis of central nervous system 366
tuberculous meningitis 366, 695, 367f
tuberous sclerosis 72, 284, 380, 380f, 688, 688f
tubular bones 714f
tumour
excised 275f
markers 272
thrombi 685f
of bone 481

turner’s syndrome 66f
types of
vaccine 528
biliary atresia 237
choledochal cysts 238
haemangioma 282
handwash 825
mutation 71
needle 833
sample 614
typhoid fever 538
Typical overlapping fingers 65f

U
Ulceration 491, 492f
Ulcerative colitis 134, 134t, 135f
Umbilical hernia 234
Umblicated papules 295f
Uncomplicated ureteral duplication 718f
Undescended testes 249f
Unerupted super numerary teeth 499f
Unexplained
death 44
symptoms 643
Unfavourable histopathology 262
Uniparental disomy and imprinting 67
Univentricular heart 185
Untreated coeliac disease 138f
Upper
fullness 685f
airway 192
eyelid ptosis 731f
eyelids 331f
gastrointestinal
contrast study 676f
tract contrast study 209f
gi endoscopy 328f
lid corrections 731f
limb trans-radial amputee 779f
renal moiety 718f
respiratory tract 102, 105
infection 105
Urea
breath test (Helicobacter pylori infections)

850
cycle disorders 420
Ureteral duplication 717
Ureterocalicostomy 246
Ureteropelvic junction obstruction 723f
Urinalysis 836
interpretation 837
Urinary
catheterisation in male and female 834
system 340
tract 845
imaging 345
infections 248, 344
nephrocalcinosis 722
stones 722
Urine 614
leak 246
output monitoring 201
Urogenital tract 509

Urology 244
Urticaria 294, 294f
Uterus 268
Uveitis 588, 589f, 590

V
vaccination
and weaning 48
history 100
vaccine related factors 528
vaccines 526
vagina 268
valgum 90f, 473f
valgus alignment 474f
vancomycin therapy 617
variants diagram 174f
varicella virus (chickenpox) 556
various forms of abuse 786
various types of vaccines used for active

immunisation 527
varum 90f, 473f
vascular
anomalies 280, 282, 751
ring 175, 176f, 177f
tumours 280
vasculitic syndromes 336
Vasopressin deficiency 435t
vein of galen malformation 688, 689f
velocardiofacial syndrome 68f
venepuncture 826
venous access 838, 839
ventilation 32
ventilator strategies 205
ventilatory support 400
ventricular
puncture 845
septal defect 162, 162f, 184, 671
tachycardia/fibrillation 183
vermis 696f
vernal 579f
vernal keratoconjunctivitis 579
vertebral bodies 702f
vertical
and horizontal mid-face fracture patterns

745f
talus 468, 569t
Vesicoureteric reflux 247, 345f, 723
vesiculobullous disorders 491
viral
infections 495
of liver 145
pneumonia 657
pneumonias 105, 657f
warts 295
visceral variety 133
visible abnormal anal opening 216
visual
acuity 569
measurement 570
assessment 569
functions 571
impairment 595f
information 572f

Page 904

Hutchison's Paediatrics 884884

vitamin
A deficiency 83
in childhood 84
A supplementation
with immunisations 85t
B deficiencies 93
B1 deficiency 93
B12 deficiency 95, 303
B2 deficiency 94
B6 deficiency 95
C deficiency 92
D deficiency 89
D metabolism 89
E deficiency 97
k deficiency 97
vitiligo 283, 284f
volumatic with metered dose inhaler 110f
volved small bowel 676f
von Hippel-Lindau disease 381
von Willebrand disease 316
vulva 268

W
Waddling gait 464
Walking 462
Wall masses 668

Water House-friderichsen syndrome 363
Water-soluble contrast study 678f
Wave sign 665f
Wegener’s granulomatosis 339
Weighs 55t
Weight
babies 56t
height and body surface area 782
Wet lung 34
Wheelchair 771f
White
cell
disorders 604
types and their disorders 606t
cells 300
lesions 492
matter 692f
oedema 695f
spectacle sign 313f
Whole bowel irrigation 402
Wilms’ tumour 258, 259f, 683, 724, 724f, 725f
of left kidney 724f
Wilson’s disease 378, 378f
hepatolenticular degeneration 144
Window settings 715f
Wiskott-Aldrich syndrome 298, 315, 517

Wolff-parkinson-White syndrome 182f
Wound 832f
coverage 202
preparation 831

X
Xanthochromic subdural fluid 845f
Xerophthalmia and nutritional corneal ulceration

581
X-linked
agammaglobulinaemia 516
dominant inheritance 61
ichthyosis 297f
recessive inheritance 60

Y
Yolk sac tumour recurrence 276f

Z
Zinc
in child health 86
supplementation 155
Zygomatico-facial nerve branches 748f
Zygomatico-orbital injuries 746

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